Infliximab infusion is not yet FDA-approved for psoriasis but has been reported to be very effective for plaque psoriasis. We report 2 patients without a history of psoriasis who after administration of infliximab for their inflammatory bowel disease experienced new onset, biopsy confirmed psoriasis.

Efalizumab is one of the new biologic therapies targeting T-lymphocyte activity for the treatment of chronic plaque psoriasis. Common adverse effects include headaches, nonspecific infection, nausea, chills, and fever. Rebound of psoriasis following discontinuation of the drug has been reported. Relapse events can manifest as recurrent plaque psoriasis, guttate psoriasis, psoriatic erythroderma, and pustular psoriasis. We report a second case of withdrawal flare resulting in generalized pustular psoriasis.

Palmoplantar psoriasis is a chronic debilitating type of psoriasis. Treatment options for this disease are poorly studied. This chart review evaluated the use of methotrexate alone and in combination with 7 other systemic therapies in 48 patients with palmoplantar psoriasis. The findings demonstrate that methotrexate is a relatively well-tolerated and effective treatment for palmoplantar psoriasis, amenable as either monotherapy or in combination with other systemic agents.

J Drugs Dermatol. 2015;14(8):888-892.

No abstract details for the moment.

Acitretin is a second generation retinoid used in the treatment of psoriasis. It has shown particular efficacy in the treatment of pustular or erythrodermic psoriasis. A case of a patient who was being treated for plaque psoriasis with acitretin, who subsequently developed erythrodermic psoriasis is reported. The patient’s erythroderma promptly resolved after discontinuing acitretin and initiating treatment with cyclosporine. Acitretin has been reported to induce erythrodermic psoriasis on occasion, but is more frequently reported as a treatment for it.

Interferon-alpha can exacerbate existing psoriasis and induce de novo psoriasis and psoriatic arthritits. The exact underlying mechanism is not very well understood. It is not a contraindication to treat patients with pre-existing psoriasis with interferon-alpha. In these patients interferon-alpha should be used with care and only if the potential benefits justify the potential risk. Control of psoriasis prior to initiation of interferon-alpha and simultaneous antipsoriatic therapy while on interferon-alpha are essential. We would like to report a 61-year-old male patient with stable psoriasis for over 20 years, who experienced exacerbation of his psoriasis after receiving interferon-alpha for chronic myeloid leukemia. The association between the interferon-alpha therapy and the exacerbation of his psoriasis was only recognized on rechallenge at the stage he was referred to our department.

BACKGROUND: HIV-associated psoriasis is well-documented. Genetic, cellular, and cytokine profiles have been used as evidence to suggest psoriasis activates antiviral pathways. There has been a lack of epidemiologic evidence investigating whether psoriasis patients have lower HIV viral counts compared to non-psoriasis patients.

OBJECTIVE: Compare the viral load set point of HIV positive patients with and without psoriasis.

METHODS: A retrospective matched cohort study of HIV positive patients with and without psoriasis using the Kaiser Permanente Southern California Health Plan database.

RESULTS: We identified 101 HIV-positive psoriasis cases; 19 met inclusion criteria and were matched with 3-5 control patients; 94 total patients were analyzed. The mean age was 41.4 (12.07) years and 83% were male. Overall, the median log of the viral load of cases was slightly higher than controls (4.3 vs 4.2; P less than 0.01).

CONCLUSIONS: The serum viral load set point of patients with HIV and psoriasis was slightly higher than the viral load set point of HIV patients without psoriasis.

J Drugs Dermatol. 2017;16(4):372-377.

Various topical and systemic treatments have shown effi cacy in plaque and palmoplantar psoriasis; however, studies regarding effi - cacy in inverse psoriasis are few. The authors present a case of a patient with severe inverse psoriasis who was successfully treated with efalizumab, resulting in complete and sustained remission during prolonged maintenance therapy.

An estimated 2.1% of Americans have psoriasis and approximately 30% of them have moderate to severe psoriasis. Although the disease is not associated with mortality, it has a significant impact on health-related quality of life among patients. Several therapies are available for psoriasis including topical agents, phototherapy, and systemic medications. Recently, effective yet expensive biologic agents have been added as treatments for moderate to severe psoriasis. Biologics are recommended in patients for whom all other available treatment options have failed. This extensive review provides important information on the clinical and patient-related outcomes associated with the biologic agents used in psoriasis.

BACKGROUND: Costs for psoriasis have increased in recent years, in part due to the introduction of biologic agents.
OBJECTIVE: To identify the most common and most costly (from the payer perspective) drugs used in the treatment of psoriasis.
METHODS: We analyzed patient data from a large claims-based database in order to identify the most common and most costly medications used in the treatment of psoriasis from 2010 to 2014.
RESULTS: The three most common psoriasis medications, accounting for 81.1% of all psoriasis medications, were topical corticosteroids. The three most costly drugs, accounting for only 9.6% of all psoriasis medications, were biologics, accounting for 86% of the cost of psoriasis medications.
CONCLUSIONS: Biologic agents are used far less commonly in the treatment of psoriasis than topical treatments. Despite the relatively small number of patients using biologic agents, biologics are responsible for a large proportion of the cost of psoriasis pharmacotherapy.

J Drugs Dermatol. 2016;15(3):305-308.

OBJECTIVES: To stratify MI risk reduction in those treated with a TNF inhibitor for psoriasis only, psoriatic arthritis only, or both psoriasis and psoriatic arthritis.
DESIGN: Retrospective cohort study
SETTING: Between January 1, 2004 and November 30, 2010
PARTICIPANTS: At least 3 ICD9 codes for psoriasis (696.1) or psoriatic arthritis (696.0) (without antecedent MI.
INTERVENTION: None
MAIN OUTCOME MEASURE: Incident MI
RESULTS: When comparing to those not treated with TNF inhibitors (reference group), of those treated with TNF inhibitors: those with psoriasis only (N= 846) had a significant decrease in MI risk (hazard ratio (HR), 0.26; 95% CI, 0.12-0.56); those with psoriatic arthritis only (N= 112) had a non-significant decrease in MI risk (HR, 0.86; 95% CI, 0.28-2.70); those with both psoriasis and psoriatic arthritis (N= 715) had a non-significant decrease in MI risk (HR, 0.76; 95% CI, 0.47-1.24).
CONCLUSIONS: In the TNF inhibitor cohort, those with psoriasis only have the strongest association with MI risk reduction, followed by those with psoriatic arthritis only, and then followed by those with both psoriasis and psoriatic arthritis.

J Drugs Dermatol. 2014;13(8):932-934.

Psoriasis is a chronic immune-inflammatory–mediated disease that can predispose patients to other inflammatory conditions. For example, individuals with psoriasis are at increased risk for insulin resistance, obesity, dyslipidemia, and hypertension— components that characterize the metabolic syndrome. The metabolic syndrome is an important driver of adverse cardiovascular outcomes. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), and other factors that are overproduced in patients with psoriasis likely contribute to the increased risk for development of metabolic syndrome. This article reviews the association of psoriasis with metabolic syndrome, as well as the impact of biologic agents that are currently used to treat psoriasis (ie, TNF antagonists) on risk factors for metabolic syndrome.

Documentation of psoriatic eruptions occurring with the initiation of various pharmacotherapy agents has been reported in the literature. Two such agents include lithium and beta-blocking drugs. By understanding the mechanism by which these drugs induce and exacerbate psoriasis, we may gain further understanding of the disease process of psoriasis as well as how to treat this side effect. This paper reviews the literature that has examined the mechanism by which lithium and beta-blockers may induce and exacerbate psoriasis. Mechanisms involving both immunologic and non-immunologic factors have been examined in various studies. No consensus has been reached and further investigation is needed. However, findings such as improvement with inositol supplementation in cases of lithium-induced and -exacerbated psoriasis and disparate histologic presentation of beta-blocker-induced psoriasis provide suggestions that both the origin and treatment of drug-induced psoriasis may be different than psoriasis that is unrelated to medications.

The risk factors of cardiovascular disease and other disease comorbidities appear to be more common in patients with psoriasis compared with the general population. To support this concept, the association between psoriasis and cardiovascular disease and other comorbidities was analyzed using data collected from 40 730 patients in the National Health and Wellness Survey (NHWS) during May and June 2004. A case-control study was conducted with data from 1127 patients with psoriasis and a matched cohort of nonpsoriasis patients. Psoriasis patients were significantly more likely to have cardiovascular comorbidities, including hypertension, hypercholesterolemia, and diabetes, compared with nonpsoriasis patients. Other comorbidities significantly associated with psoriasis were arthritis, depression, sleep disorder/insomnia, chronic obstructive pulmonary disease, and gastroesophageal reflux disease. Responses to this large survey confirm that patients with psoriasis have a higher rate of cardiovascular risk factors and other comorbidities compared with patients without psoriasis.

Pustular psoriasis is an uncommon variant of psoriasis characterized by widespread pustules on an erythematous background. Recent reports document the efficacy of immunobiologic agents such as infliximab in the treatment of pustular psoriasis. We present a patient that developed cutaneous and pathologic changes consistent with pustular psoriasis while receiving treatment with infliximab for chronic ulcerative colitis. More long-term studies need to be conducted in order to fully understand this paradoxical reaction as well as the mechanism of action and side effect profiles of infliximab and other immunobiologic agents.

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European population. Over the last several years, one of the major focuses in psoriasis research has been the development of novel biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention, with the hope that such specificity will result in fewer side effects than traditional therapies. In addition to these therapies, there are also oral medications in development for psoriasis. The goal of this article is to review oral tazarotene, a novel retinoid, and oral pimecrolimus, a novel macrolactam therapy, for the treatment of moderate to severe psoriasis.

Although the precise pathogenesis is not known, vitiligo appears to be an autoimmune disease involving T cell-mediated melanocyte destruction. Efalizumab, a recombinant, humanized monoclonal antibody, targets T cells, the key mediators of the immunopathogenesis of psoriasis. Although a concomitant presentation of vitiligo with psoriasis is uncommon, several cases have been reported previously in the literature. A case of a patient with vitiligo and psoriasis who was treated with efalizumab to alleviate the symptoms of psoriasis is described. Over the course of the diseases, the patient had been treated unsuccessfully with numerous therapies. The patient initiated efalizumab with a 0.7 mg/kg conditioning dose and then continued on 1 mg/kg weekly. After 2 months of efalizumab therapy, the psoriasis symptoms were reduced, and the vitiligo had visibly improved in some areas. The patient has remained on efalizumab therapy with no evidence of an exacerbation of vitiligo. The management of acute flares is also discussed. This case is illustrative of a patient with psoriasis and vitiligo who was treated successfully with efalizumab.

TNF-alpha inhibitors are used to treat numerous inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease. Recent reports have illustrated the paradoxical development of psoriasis with TNF-alpha inhibitor therapy. We present here a review of 142 cases of new-onset psoriasis with infliximab, adalimumab, and etanercept therapy. This review illustrates the diverse conditions responsible for TNF-alpha-inhibitor induced psoriasis, the variable time prior to psoriasis development, and the most predominant forms of psoriasis. An analysis of the various therapeutic regimens applied may help provide guidelines for patient management.

J Drugs Dermatol. 2013;12(8):939-943.

Psoriasis continues to be one of the most common and frustrating conditions that dermatologists and their patients face on a daily basis. Novel developments in basic science bring us closer than ever to understanding the pathogenesis of psoriasis. At the same time, the advent of biologic immunomodulators has opened doors in terms of treatment options and a better understanding of the underlying etiology of psoriasis. Genes involved in the immune system, keratinocyte differentiation, and vascular hyperplasia have all been implicated in psoriasis.

Recently, the biologics have emerged as a new class of drugs for systemic therapy of psoriasis with efalizumab (Raptiva®) being one of the most recently FDA-approved agents. We report a case of a 34-year-old Caucasian male who experienced psoriasis rebound during a 7-week lapse in treatment with subcutaneous efalizumab 0.8 mg/kg/week, which he had been using for 4 weeks up to that point. The patient then restarted efalizumab, but his psoriasis continued to worsen causing him to be admitted for Goeckerman day care. He rebounded again 4 weeks following his ultimate discontinuation of efaluzimab despite intensive therapy with the Goeckerman regimen. This case is reported to highlight the recent findings that psoriasis rebound, defined as psoriasis area and severity index (PASI) of 125% or greater or morphology change, has been associated with both the use and the discontinuation of efalizumab.

Historically, severe psoriasis frequently required inpatient hospitalization for several weeks to reduce symptoms and prevent morbidity and mortality. Despite declining hospitalization rates there remain patients who undergo severe, acute psoriasis exacerbations requiring inpatient care. The majority of the literature describes the treatment of psoriasis in the outpatient setting. We review the inherent differences between the inpatient and outpatient management of psoriasis along several dimensions and discuss an approach to the inpatient treatment of severe psoriasis based upon therapeutic rate of onset, efficacy, and safety. The inpatient setting benefits from and lends itself to use of rapid acting, highly effective agents. Given the acute nature of psoriasis inpatient episodes, the risks associated with long-term use of a treatment are far less important in inpatient setting treatment planning than they are in the outpatient setting.

No abstract details for the moment.

Psoriasis is a chronic inflammatory disease of the skin that can have a major effect on patient quality of life. Conventional psoriasis treatments, often identified empirically, fail to meet the clinical needs for a safe and remittive therapy. These unmet needs, together with the rapid advances in understanding the molecular basis of psoriasis, have led to the development of targeted biologic therapies. Using recombinant DNA technology, a new generation of therapeutic agents is being designed to interfere at specific pathogenic steps that involve T-cells or T-cell-mediated immune responses. These targeted therapies promise improved tolerability and safety in the treatment of psoriasis. Furthermore, they will redefine clinical response in psoriasis by providing long-lasting remissions of disease and extended treatment-free periods.

INTRODUCTION: Nail psoriasis is challenging to treat. The few currently available therapies are limited in efficacy, and often produce unfavorable side effects. A plant extract widely used in Traditional Chinese Medicine, indigo naturalis (Qing Dai), is presented in this review as an alternative topical treatment for skin and nail psoriasis. The purpose of this article is to present information on a viable alternative treatment with a favorable side effect profile for a difficult disease to treat.
METHODS: A PubMed search for the term “indigo naturalis” was performed, and literature from 2006 to the present relevant to indigo naturalis and treatment of psoriasis and nail psoriasis was reviewed.
RESULTS: Indigo naturalis shares several therapeutic mechanisms with current psoriasis treatments, such as regulation of keratinocyte proliferation and differentiation, restoration of epidermal barrier function, and reduction of inflammatory processes. Clinically, it is well tolerated.
CONCLUSION: Recent research of indigo naturalis suggests that it is a safe, inexpensive, and effective alternative topical treatment for skin and nail psoriasis.

J Drugs Dermatol. 2016;15(3):319-323.

Interleukin 12 (IL-12) is an important cytokine produced by a variety of immune effector cells that leads to a type 1 helper T cell (Th1) response. IL-12 also directs T cells to the skin via induction of cutaneous lymphocyte antigen (CLA) expression. In this article we report the current understanding of the immunobiology of IL-12, reviewing its structure, receptor, and function. We also discuss the role of IL-12 in the pathogenesis of psoriasis. Some effective conventional psoriasis treatments alter IL-12 levels. Importantly, specific antibodies directed against IL-12 may prove useful against psoriasis but may also act by targeting IL-23 in addition to IL-12.

Verrucous linear segmental psoriasis (VLSP) is invariably recalcitrant to treatment. It is a distinct variant of psoriasis that frequently is considered a form of a verrucous linear, epidermal nevus.1 The hypertrophic nature of the plaques makes treatment particularly chal- lenging. The authors present a case of verrucous linear psoriasis of the right leg that responded to radiation therapy.

The Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA) are commonly used, but fail to measure quality of life and the patient’s perception of well-being. In response to these limitations, the National Psoriasis Foundation (NPF) Medical Advisory Board has developed the NPF Psoriasis Score (NPF-PS). This article evaluates the degree of concordance between NPF-PS, PASI, and PGA scores via an investigator-initiated, single-center, double-blind, placebo-controlled study of thirty-three patients with moderate to severe plaque psoriasis.

Our results indicated that NPF-PS was strongly correlated with PASI and PGA in this study, while better reflecting patient perception. This is the first report of a double-blind placebo-controlled study demonstrating this concordance.

Psoriasis is a common, frustrating problem for dermatologists and patients. Long-held notions about the need to use thick, greasy corticosteroid ointments for psoriasis contributed to frustration for many patients. Fortunately, the general approach to managing psoriasis is changing. The purpose of this article is to describe key components of psoriasis management with a focus on the changing paradigm for treating the disease. In addition to making the right diagnosis and prescribing the right treatment, key elements of psoriasis management include establishing a strong physician-patient relationship, educating patients about the disease and recognizing the importance of adherence to topical treatment. In light of the tendency toward poor adherence, use of a fastacting agent in a vehicle that patients are willing to use is critically important for successful disease management.

A case of psoriasis and psoriatic arthritis in a 38-year-old white male patient infected with human immunodefi ciency virus (HIV) treat- ed safely and effectively with mycophenolate mofetil (MMF) is reported. Treatments for psoriasis and psoriatic arthritis are manifold, including topical, oral, intramuscular, intravenous, and subcutaneous therapies. These indicated treatments for psoriasis and psoriatic arthritis result in suppression of the immune system.

INTRODUCTION: A significant portion of patients with psoriasis have scalp and nail involvement. It has been reported that 40% to 45% of patients with psoriasis have nail psoriasis, and up to 80% have scalp involvement. Nail and scalp psoriasis have often been found to be difficult to treat, due to the poor penetration and poor compliance of topical medication. Oral and biologic therapies have shown significant efficacy but often with undesirable side effects. Herein, we analyze the efficacy of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor, in the treatment of nail and scalp psoriasis at 16-, 32-, and 52 weeks.
METHODS: We reviewed the results of the phase IIb and phase III clinical trials for apremilast in treating nail and scalp psoriasis.
RESULTS: In ESTEEM 1, patients on apremilast showed a 22.5%, 43.6%, and 60.2% improvement in NAPSI at weeks 16, 32, and 52. 33.3%, 45.2%, and 63% of patients achieved NAPSI-50, respectively. In ESTEEM 2, patients on apremilast showed a 29%, 60%, and 59.7% improvement in NAPSI at weeks 16, 32, and 52, with 44.6%, 55.4%, and 68.6% of patients achieving NAPSI-50. In PSOR-005 at week 16, patients on a dose of 30 mg twice weekly had a 42.9% improvement in NAPSI with 45.5% reaching NAPSI-50. For scalp psoriasis, 46.5%, 37.4%, and 73% of patients achieved an Sc-PGA of 0 or 1 at weeks 16, 32, and 52 in ESTEEM 1. In ESTEEM 2, 40.9%, 32.4%, and 62.5% of patients achieved an Sc-PGA of 0 or 1 at weeks 16, 32, and 52.
CONCLUSION: With its limited safety profile of only diarrhea and headache and no additional lab requirements, apremilast may be a safer and more convenient alternative for patients with severe nail and scalp psoriasis.

J Drugs Dermatol. 2016;15(3):272-276.

Hand and foot psoriasis can appear in a plaque-type or pustular-type form. Any form of psoriasis that occurs on the hands and feet can have a debilitating effect on the patient’s daily functions. Here we present a case series of patients with plaqueor pustular-type hand and foot psoriasis whose conditions were successfully managed with the biologic agent efalizumab. In many of these patients, the disease was refractory to multiple systemic psoriasis treatments. Treatment with efalizumab was effective and well-tolerated, with few adverse events. Many of the patients described here reported an improvement in both their physical functioning and health-related quality of life. The efficacy of efalizumab in treating these cases of hand and foot psoriasis suggests that it may provide therapeutic benefit.

Infliximab is a chimeric, murine-human, monoclonal antibody against tumor necrosis alpha which has shown great efficacy in the treatment of psoriasis. Serum sickness, which is an immune complex mediated syndrome consisting of a cutaneous eruption, fever, arthritis, edema, and lymphadenopathy, has been described in several patients receiving infliximab for the treatment of Crohn’s disease. However, to our knowledge, this type of reaction has not been well described in a patient treated with infliximab for psoriasis. We describe a patient who developed serum sickness while receiving infliximab for psoriasis and discuss the pathogenesis, diagnosis, and treatment of serum sickness. We believe that with the increasing use of infliximab for psoriasis, more cases of serum sickness will occur. Therefore, awareness of this adverse effect is essential.

Psoriasis is a chronic inflammatory skin disease where the use of topical corticosteroids is a mainstream treatment. However, the continuous use of high potency topical corticosteroids is limited by a variety of well known adverse events which include, atrophy, and telangiectasia. Also, inhibition of lipid synthesis by steroids can cause impairment of the epidermal barrier, which is already disrupted in most of the inflammatory cutaneous disorders such as psoriasis. This will further lead to increase transepidermal water loss (TEWL), decreased hydration, dry skin, and irritation. On the other hand, topical vitamin D analogs directly affect keratinocyte proliferation and differentiation as well as modulation of epidermal lipids and antimicrobial peptides. Although the exact mechanism of action of topical vitamin D analogs is not well understood in the treatment of psoriasis, their efficacy and safety has been shown in several clinical trials over the years and they are widely used for psoriasis. Therefore, combination of topical steroids and vitamin D analogs may be a logical option for the treatment of psoriasis.

J Drugs Dermatol. 2015;14(10):1113-1116.

Psoriasis and psoriatic arthritis are immune-mediated, chronic, inflammatory diseases that place a heavy burden on the lifestyle of patients affected. Current understanding of the pathophysiology of these conditions has produced very encouraging new medical developments, largely a consequence of research that has targeted precise elements of the immune cascade, expanding the repertoire of therapeutic options available to dermatologists. Promising new treatments, such as antibodies to interleukin-12 and -23, show superior efficacy and safety in treating psoriasis; the more sophisticated tumor necrosis factor antagonists significantly improve symptoms of rheumatic and psoriatic arthritis and may also be effective in the treatment of plaque psoriasis. In this article, innovative, new treatments for psoriasis and psoriatic arthritis are critically reviewed.

Psoriasis of the hands and feet is highly debilitating and difficult to treat. It may be of a plaque-or pustular-type, or a combination of the two. Efalizumab (Raptiva®, Genentech Inc), a humanized monoclonal antibody that inhibits critical T cellmediated processes, is approved by the FDA for the treatment of adult patients with chronic moderate to severe plaque psoriasis. We present the cases of 7 patients who suffered from extensive hand and foot psoriasis recalcitrant to treatment. Each patient was treated with 1 mg/kg/wk of efalizumab and responded rapidly to treatment with favorable results appearing within 1 to 4 months. Patients were able to resume previous work responsibilities and no longer suffered from difficulties with ambulation. Efalizumab was effective for the rapid treatment of these 7 patients with psoriasis of the hands and feet.

Increased understanding of psoriasis has led to a shift in treatments from non-specific immunosuppressants to targeted biologics. Studies in psoriasis have demonstrated minimal risk and substantial benefit. As a result, dermatologists and patients are more frequently choosing biologics as first-line treatments for moderate-to-severe disease as our biologics options have recently increased.

The scalp is one of the regions of the body most commonly affected by psoriatic lesions. While the head represents only 10 percent of the body’s surface area, the consequences of scalp psoriasis are disproportionate to the area, as it can be seriously debilitating and presents social and emotional distress to the affected individual. Scalp lesions are often well-demarcated and may have thick gray or white scale; patients with scalp psoriasis frequently complain of pruritus and shedding of scale. Current treatment modalities— including phototherapy, topical corticosteroids, topical vitamin D analogues and conventional systemic therapies—have produced unsatisfactory results for patients with moderate-to-severe scalp psoriasis due to difficulties in administration to the disease site, poor compliance, toxicity and inadequate long-term efficacy. The emergence of biologic therapies as an effective modality for the treatment of plaque psoriasis may provide another option for patients suffering from plaque psoriasis of the scalp.

Psoriasis in HIV-infected patients poses a distinct challenge to the dermatologist due to its increased severity, tendency to be refractory to common treatment modalities, and necessity for cautious use of immunosuppressive agents. Tumor necrosis factor-α inhibitors have been shown to be safe and effective for the treatment of psoriasis in the general population, but their role in the treatment of HIV-positive patients is still unclear. The use of the tumor necrosis factor-α inhibitor adalimumab for the treatment of psoriasis in HIVpositive patients has yet to be reported. We present the case of a 49-year-old HIV-positive man with severe plaque psoriasis who has been successfully treated with adalimumab for the past 30 months with no adverse events related to treatment.

J Drugs Dermatol. 2014;13(7):869-871.

Psoriasis is a common skin condition affecting approximately 2.6% of the population in the US. The most effective current therapies for psoriasis have suppressive activity against T lymphocytes directly or by modulating the biologic effects of inflammatory cytokines. Tacrolimus has been used successfully to treat a number of T cell-mediated diseases. UVA1 has been shown to induce T lymphocyte apoptosis. Combination treatment is commonly used in the management of psoriasis. Therefore, this pilot study was performed to evaluate if the combination of medium-dose UVA1 (50 J/cm2) and tacrolimus ointment is effective for the treatment of palmar plantar psoriasis. A total of 5 patients completed the study of 30 UVA1 treatments, and another patient completed half of the treatments. No dramatic changes in plaque thickness or scaling were seen with either tacrolimus alone or with the combination of tacrolimus and medium dose UVA1 on palmar or plantar psoriasis.

BACKGROUND: Increased knowledge of the molecular regulatory mechanisms that contribute to the pathogenesis of psoriasis and other inflammatory diseases has created new opportunities for the development of targeted drug therapy for inflammatory conditions. Two new oral medications, apremilast and tofacitinib, have been developed for their immunomodulatory properties, and their potential efficacy in treating psoriasis is being evaluated.
METHODS: We reviewed phase III randomized, placebo-controlled clinical trial results for apremilast and tofacitinib for efficacy and safety in psoriasis.
RESULTS: Psoriasis Area and Severity Index (PASI) 75 after 16 weeks for apremilast was between 28.8% and 33.1%. PASI 75 was 39.5% after 12 weeks on tofacitinib 5 mg, and 63.6% after 12 weeks on tofacitinib 10 mg. Common side effects for both drugs included nasopharyngitis and upper respiratory tract infections. Gastrointestinal disturbance was common for apremilast. Dyslipidemia and infections were more common with tofacitinib than placebo.
CONCLUSION: Both new oral medications, apremilast and tofacitinib, appear to be effective in treating psoriasis.

J Drugs Dermatol. 2015;14(8):786-792.

Alcoholism is a risk factor in the worsening of psoriasis. The authors present two cases of flared severe psoriasis in alcoholic patients showing dramatic improvement of their skin disease using treatments directed towards correcting abnormalities commonly found as sequelae of alcoholism such as endotoxin production, low serum magnesium levels and elevated plasma homocysteine levels.

Topical corticosteroids are the most common treatment agent for psoriasis in the United States (U.S.). Conventional dermatologic wisdom holds that ointment preparations provide the highest potency (due to their occlusive nature and moisturizing ability) and are best suited for psoriasis. This article presents evidence challenging the conventional belief that ointment vehicles are necessarily best for psoriasis. A previous systematic review of the efficacy of clinical trials of potent topical corticosteroids did not support greater efficacy or greater delivery of potent topical corticosteroids with ointment vehicles compared to other topical preparations. Moreover, preference studies demonstrate that psoriasis patients often find application of ointment to be messy, raising concerns about both short-term and long-term adherence to treatment. Recent compliance studies demonstrate that poor compliance to topical treatment is common among psoriasis patients and contributes to poor psoriasis treatment outcomes. Non-ointment topical corticosteroid products exhibit excellent efficacy in clinical practice. Much of the poor outcomes in psoriasis, even tachyphylaxis, likely relate less to actual medication failure and more to failure to apply the medication. Topical psoriasis treatment is likely to be more successful when physicians and patients discuss what type of vehicle the patient will use and plan treatment accordingly.

Psoriasis is a systemic inflammatory disease. Effective management requires treatment with agents targeting inflammation in skin, joints, and other tissues. Biologics for psoriasis are directed at more specific targets, have a better safety profile, are better tolerated, and are more effective than conventional systemic agents. Despite these advances, many patients with psoriasis remain undertreated, and overall patient satisfaction remains low. The dichotomy between ideal therapeutic outcomes and suboptimal outcomes (which are currently commonplace) is likely largely due to misperceptions about psoriasis and biologic treatments. This article discusses these misperceptions, including the notions that psoriasis is a benign disorder, and that conventional systemic therapies are safer than biologics and adequate for most patients with moderate-to-severe disease. We present practical and evidence-based discussions to refute these misconceptions and provide useful resources for providers and patients that support access to advanced therapies. We believe that biologics represent optimal treatment for most patients with moderate-to-severe psoriasis, and until more effective approaches are generated, these efficacious and target-specific approaches should become the standard of care.

J Drugs Dermatol. 2015;14(8):805-812.

Use of botulinum neurotoxin A (BoNTA) for treating inflammatory skin disease is an underexplored area in medical dermatology. Preclinical mouse studies have demonstrated efficacy of abobotulinumtoxinA in improving psoriasiform skin inflammation. We describe sustained local clearance of a psoriasis plaque in a patient following a single off-label injection of intradermal abobotulinumtoxinA. BoNTA may offer a novel therapeutic approach for treating recalcitrant plaque psoriasis.
Case reports and anecdotal evidence suggests that onabotulinumtoxinA may be useful for treating inverse psoriasis.1,2 We previously reported an improvement in skin phenotype in a preclinical mouse model following a single intradermal injection of abobotulinumtoxinA.3 Here we present a patient case report demonstrating efficacy of abobotulinumtoxinA in reversing plaque psoriasis.

J Drugs Dermatol. 2014;13(11):1407-1408.

BACKGROUND: Many factors, including patients' methods of payment, may influence psoriasis treatment decisions.
OBJECTIVE: To characterize psoriasis treatments by patients' types of payment in the US outpatient office setting.
METHODS: Using the National Ambulatory Medical Care Survey (NAMCS), a large survey that samples outpatient office visits to US non-federally funded physicians, visits linked with sole diagnoses for psoriasis (ICD-9-CM: 696.1) were identified. There were 545 unweighted records. The types and number of treatments prescribed at these visits were categorized by expected major payment type to be used for the visit.
RESULTS: Mainstay psoriasis therapies such as vitamin D analogs and clobetasol were prescribed regardless of payment type. Retinoids were also within the most frequently prescribed psoriasis medications for all payment types, however they were less frequently prescribed than vitamin D analogs. Payment type did not have a significant effect on the number of medications prescribed at psoriasis visits.
LIMITATIONS: Data on treatment adherence and filling of prescriptions are not included in the NAMCS database.
CONCLUSION: Prescribing patterns for psoriasis medications are similar across payment type. Additional factors appear to modulate therapy choice for patients with psoriasis.

J Drugs Dermatol. 2013;12(10):1095-1097.

Targeted phototherapy has been utilized in the past few years for the treatment of various dermatoses. In this article, we summarize the experience of using 308-nm excimer laser at Henry Ford Hospital, Detroit, MI, for the treatment of psoriasis, vitiligo, palmoplantar psoriasis, and hand dermatitis. A total of 34 patients were treated between January 2003 and February 2005. Of the 28 patients with psoriasis, over 80% had greater than 75% improvement after an average of 12 treatments. While the number of patients was small, excimer laser showed promising results for palmoplantar psoriasis. Possibly due to patient selection bias, we have not had the same success as other studies for the treatment of vitiligo with this modality.

No abstract details for the moment.

Pustular and erythrodermic psoriasis can be a debilitating and recalcitrant disease which may result in secondary complications such as sepsis, electrolyte imbalance, renal failure, and heart failure. We report a case of a 46-year-old patient with lifethreatening erythrodermic psoriasis who responded rapidly to intravenous infliximab.

Psoriasis and psoriatic arthritis (PsA) are chronic inflammatory disorders. Efalizumab targets several T-cell interactions central to psoriasis immunopathogenesis. Etanercept and infliximab are antitumor necrosis factor (anti-TNF) agents that modify the inflammatory and cell-mediated immune responses involved in the pathogenesis of psoriasis and PsA. All 3 agents are approved for the treatment of plaque psoriasis, and etanercept and infliximab are also approved for the treatment of PsA. Twenty patients with psoriasis and PsA have been successfully treated with a combination of efalizumab (1 mg/kg/wk) and etanercept (25 mg or 50 mg/wk) or infliximab (5 to 6 mg/kg). To date, no serious adverse events have been reported. Combination therapy was well tolerated and effectively controlled both skin disease and arthritis. The complementary activity of efalizumab with an anti-TNF agent is most likely attributable to their differing mechanisms of action. Further investigation is warranted.

INTRODUCTION: Psoriasis is a chronic, inflammatory autoimmune disease that affects about 3% of the general population in the United States with 17% suffering from moderate to severe psoriasis. The disease process is believed to be mediated by tumor necrosis factor (TNF)-α and cytokines secreted by specialized T-cell populations including Interleukin (IL)-17, IL-22, and Interferon (IFN) γ. IL-17 plays an important role in psoriasis. In this study we evaluated the expression of IL-17A in variants of psoriasis including plaque, palmoplantar, scalp, pustular, and guttate subtypes via immunohistochemistry (IHC).
METHODS AND MATERIALS: A search of the University of Miami Dermatopathology database was performed to identify all available patient specimens within the various subtypes of psoriasis. IL-17A IHC staining was performed using 4 μm paraffin skin sections. 1:25 dilution of IL-17A antibody was used. Stained slides were analyzed using a semi-quantitative scoring method ranging from negative to three plus.
RESULTS: Palmoplantar and pustular psoriasis cases showed consistently strong IL-17A staining. Plaque psoriasis cases showed intermittent to strong IL-17A staining. The results in the scalp and guttate psoriasis cases showed variable results.
CONCLUSION: The results of our study suggests the significant role of the cytokine IL-17A in the development of palmoplantar and pustular psoriasis. However, scalp and guttate subtypes showed variable expression from negative to strongly positive, which demonstrates a case by case basis expression of IL-17A. Therefore, exploring the IHC characterization of subtypes of psoriasis will help dermatologists better understand the pathogenesis of each subtype and help clinicians optimize treatments.

J Drugs Dermatol. 2015;14(10):1133-1136.

Alefacept is the first biologic agent approved for the treatment of chronic plaque psoriasis in the United States. Alefacept, administered intravenously (IV) or intramuscularly (IM), was found to be well tolerated, safe, and efficacious in two pivotal phase 3 studies in patients with moderate to severe psoriasis. Treatment with IV alefacept was associated with a median duration of off-treatment response of 216 days (approximately 7 months). In a follow-up extension study to the phase 3 IM study, duration of therapeutic response was also examined. Patients who achieved a ?75% reduction in baseline Psoriasis Area and Severity Index (PASI 75) with the first course of alefacept 15 mg IM in the phase 3 study maintained a PASI 50 for a median duration of 209 days. In addition, the extension study demonstrated that a second course of IM alefacept is safe and well tolerated in patients with psoriasis.

Improvement in psoriasis after treatment of reactivated latent tuberculosis following initiation of TNF-α inhibitor therapy has yet to be described in the literature. The authors present a case of transient, yet significant, improvement in chronic plaque psoriasis after antibiotic therapy for reactivated TB.

J Drugs Dermatol. 2012;11(1):119-120.

Tofacitinib is a novel drug that inhibits the JAK-STAT signaling pathway. It has been approved for the treatment of psoriatic arthritis and it is under investigation for the treatment of psoriasis and other inflammatory disorders. We report a case of pulmonary cryptococcosis in an otherwise immunocompetent patient taking tofacitinib for psoriasis. We hypothesized that tofacitinib contributed to this infection through inhibition of cytokines required for differentiation of T cells and suppression of macrophage activation. As dermatologists begin to use this drug they should be aware of the potential for cryptococcocal infection, because delay of diagnosis may increase the risk of a life-threatening outcome.

J Drugs Dermatol. 2015;14(8):901-902.

Advances in the understanding of the pathogenesis of psoriasis have led to the development of biologic agents that target T cells and cytokines that play a specific role in the underlying inflammation associated with psoriasis (eg, tumor necrosis factor-α inhibitors, interleukin [IL]-12/23 inhibitors). In this review, evidence for the central role of IL-17 in the pathophysiology of psoriasis is presented, along with available clinical trial data on the selective IL-17 inhibitors in development. Three biologic agents that target IL-17 are currently in clinical development: secukinumab, ixekizumab, and brodalumab. Clinical studies to date suggest a favorable safety profile and the potential for better efficacy over the previous generation of agents, with Psoriasis Area Severity Index 75 response rates of up to 80% or greater. Fully published results of phase III studies of these agents are eagerly awaited.

J Drugs Dermatol. 2015;14(3):244-250.

BACKGROUND: Psoriasis is a common but complex chronic inflammatory skin Disease. Array-based studies can help identify therapeutic targets.
OBJECTIVE: To reproducibly assess single-gene transcriptional changes in psoriatic skin.
METHODS: We evaluated 210 top candidate genes from a first psoriasis study group (population 1), and then confirmed differential expression in a second independent psoriasis study group (population 2).
RESULTS: One hundred and thirty-eight differentially expressed genes were replicated in the 2 studies, of which 57 have not previously been reported as associated with psoriasis. This is significantly greater than the 10 expected false positives. Lesional skin vs uninvolved areas showed inflammatory and cell regulation changes.
CONCLUSION: Previously undescribed psoriasis-associated genes revealed in this study may provide potential future targets for development and assessment of novel therapeutic agents for psoriasis.

J Drugs Dermatol. 2015;14(8):794-800.

Background: Leptin, an adipocyte-derived hormone, has been shown to have several immunological effects similar to those of proinflammatory cytokines. The relationship between serum leptin, psoriasis, and obesity is still conflicted, and very few studies have investigated its role in skin diseases other than psoriasis.
Aim: To evaluate the possible relationship between serum leptin in nonobese patients with psoriasis and other randomly selected skin diseases.
Subjects and methods: Eighty subjects (40 patients with psoriasis, 20 patients with other randomly selected skin diseases, and 20 healthy controls) were included in the study. Fasting serum leptin levels of the study groups were examined by sandwich enzyme-linked immunosorbent assay.
Results: Elevated serum leptin levels were detected in both nonobese patients with psoriasis (P=.004) and those with other randomly selected skin diseases (P=.05). Leptin levels failed to correlate to the Psoriasis Area and Severity Index score of psoriatic patients. Both sexes demonstrated comparable levels of serum leptin in psoriatic patients, while female patients suffering from other skin diseases showed higher levels of serum leptin than did males of the same group.
Conclusion: Leptin may play a role in the immunopathogenesis of psoriasis and other skin diseases, even in the absence of obesity as a cofactor.

J Drugs Dermatol. 2013;12(2):e25-e29.

Psoriasis is a chronic inflammatory cutaneous disease that affects 2-3% of the general population. Up to 30% of patients with psoriasis also develop psoriatic arthritis, a chronic inflammatory and progressive arthritis. Although their precise pathogeneses remain unclear, psoriasis and psoriatic arthritis involve altered expression of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-12, IL-17, IL-22, and IL-23. The development of biologic agents that target these cytokines has greatly improved the treatment of psoriatic disease. Injection site reactions have been reported with many of these therapies. In this paper, we will present cases and review the literature on injection site reactions with the major biologic agents administered subcutaneously for the treatment of psoriasis and psoriatic arthritis.

J Drugs Dermatol. 2017;16(7):695-698.

Objective: To assess the efficacy and safety of narrowband ultraviolet B (UVB) phototherapy in dark-skinned Saudi patients with chronic plaque psoriasis. Patients and Methods: This prospective study was performed on 63 patients of chronic plaque psoriasis attending Qassim University clinics from May 2004 through June 2009. Narrowband UVB irradiation was done three times per week using the 311±2 nm wavelength. Results: Approximately 79 percent of patients achieved disease clearance (i.e., 90% or more reduction in PASI scores). The response to treatment was significantly better in females compared to males. No serious side effects were observed. Conclusion: The narrowband UVB phototherapy was found to be safe and effective in darker-skinned Saudi patients with chronic plaque psoriasis, especially among females. A longer period of treatment (minimum of six months) is recommended for complete clearance of psoriasis.

Tumor necrosis factor-alpha (TNF-?) antagonists are used to treat many autoimmune disorders including Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and more recently, psoriasis. The adverse effects of the treatment regimen for psoriasis are not as well documented as those for Crohn’s disease and rheumatoid arthritis. We report the development of acne vulgaris in 3 patients with psoriasis after initiating anti-TNF-? therapy.

Infliximab demonstrates high efficacy in treating psoriasis in a high proportion of patients. In this report we demonstrate induction of plaque (T cells, dendritic cells) and peripheral blood (T cells, monocytes) leukocyte apoptosis following a single infliximab infusion in a psoriasis patient.

BACKGROUND: The efficacy of biologic therapy in treating plaque-type psoriasis is well documented. However, there is less data for use in other psoriasis subtypes, such as erythrodermic and generalized pustular psoriasis.
OBJECTIVE: We sought to review the safety and efficacy of biologic medications in the treatment of these severe subtypes of psoriasis and to identify strategies to help clinicians optimally manage these patients.
METHODS: We searched Pubmed for English language literature that assessed the use of biologic medication to treat erythrodermic or generalized pustular psoriasis.
RESULTS: The primary literature included cases reports, cases series, and open-label, uncontrolled trials. There were no head-to-head studies or other controlled trials. In both erythrodermic and generalized pustular psoriasis, infliximab was used to treat over half of the reported cases. Other biologic medications that were successfully used included etanercept, ustekinumab, adalimumab, and anakinra. Most cases reported improvement with biologic therapy. Serious adverse events were reported in 10-12% of the patients.
CONCLUSION: Although the evidence is limited, biologic therapy appears to be effective in treating erythrodermic and generalized pustular psoriasis. In order to assess the comparative efficacy and safety of the biologic medications, larger controlled studies are needed.

J Drugs Dermatol. 2014;13(3):342-354.

Psoriasis is a common, inflammatory disease that manifests itself as lesions on the skin, which greatly impacts the physical and psychological wellbeing of those affected. The current goal of treatment in psoriasis is to improve the signs and symptoms of disease, whilst minimizing the burden of disease on patient health-related quality of life. Psoriasis can also be associated with other comorbidities such as joint disease, cardiovascular disease, and depression, which can add to the complexity of treatment.

Adalimumab is a recombinant, fully human, monoclonal antibody against tumor necrosis factor alpha (TNF-α), which blocks the interaction of TNF with both of its cell-surface receptors, with high affinity and specificity. Adalimumab is well established for the treatment of moderate–severe chronic plaque psoriasis in adults, and has more recently been approved in the European Union for use in pediatric patients with severe chronic plaque psoriasis.

Here we provide a clinical guide for adalimumab and review existing data on the efficacy and safety of originator adalimumab in moderate–severe chronic plaque psoriasis in adult and pediatric patients. We discuss short- and long-term treatment with adalimumab, and efficacy in hard-to-treat psoriasis of the scalp, hands, feet, and nails, in addition to the impact on associated pain and pruritus. We also discuss treatment optimization with adalimumab in the context of relevant clinical scenarios, and treatment of complex patients with underlying comorbidities. Finally, we examine available real-world clinical data for adalimumab in psoriasis.

J Drugs Dermatol. 2017;16(8):779-790.

Psoriasis is a common, chronic inflammatory skin disease with arthritis that may occur in a percentage of patients that varies between 5% and 42%. Many systemic agents as cyclosporine, methotrexate, acitretin, and photochemotherapy have been used for the treatment of patients affected by moderate-to-severe plaque psoriasis although they present side effects (ie, cumulative organ toxicity and lack of efficacy over time) that limit long-term use. Significant therapeutical improvement has been obtained introducing biological therapies, designed to modify and regulate immunological processes by targeting specific molecules involved in the immunopathogenesis of psoriasis. Adalimumab is a fully human recombinant antibody against tumor necrosis factor-alpha (TNF-alpha). To date, there is not much data available on the efficacy and safety of adalimumab in patients affected by moderate-to-severe plaque psoriasis. The authors report our first experience on the efficacy and safety of adalimumab in monotherapy at a dose of 40 mg every-other-week for the treatment of plaque psoriasis in patients with or without arthritis. Twenty-eight patients were treated for a period of 48 months. It was observed an improvement of the psoriasis condition as well as of patients’ quality of life and mood state.

No abstract details for the moment.

Psoriasis is a chronic, papulosquamous condition that affects up to 2% of the U.S. population. Approximately 50% of patients with psoriasis have involvement of the scalp.

This was a multicentre, randomized, vehicle-controlled, double-masked and parallel-group study. The aim was to evaluate the efficacy and safety of clobetasol propionate shampoo, 0.05% versus its corresponding vehicle in subjects aged 12 years and older with moderate to severe scalp psoriasis over a treatment period of 4 weeks. Recurrence of scalp psoriasis was assessed during a two week follow-up period.

A total of 142 subjects were treated. Results after 4 weeks demonstrated that clobetasol propionate shampoo, 0.05% was with a similar safety profile significantly more effective than its vehicle. The novel short contact shampoo formulation of clobetasol propionate is convenient and efficacious and minimizes systemic exposure while being efficient, safe and well-tolerated in the treatment of moderate to severe scalp psoriasis.

Background: Psoriasis vulgaris is one of the most common chronic skin disorders without any curative treatment. Theaim of this study was to investigate the efficacy and safety of HESA-A in the treatment of psoriasis.
Methods: In a randomized, double-blind clinical trial, 28 patients (11 male, 17 female) with chronic plaque-type psoriasis were randomly assigned to treatment and placebo groups. Patients in treatment group received HESA-A tablet 25 mg/kg twice a day orally and control group received placebo with the same method for 6 months and were followed clinically during the study.
Results: At the end of study, in the treatment group psoriatic plaques were absent (no evidence of psoriasis or complete remission) in 9 cases (64.2%) and was very mild (controlled, but not entirely cleared) in 5 cases (35.8%). Disease relief was observed in 10 (71.4%) patients after 4 months, in 2 cases (14.3%) after 5 months and in 2 (14.3%) other patients after 6 months while none of the controls showed disease improvement.
Conclusion: This study showed rapid and good efficacy and safety of HESA-A in the treatment of plaque-type psoriasis.

Optimizing combinations for psoriasis means asking patients to take control of their disease. It means balancing potency of steroids for the short-run to put out the fire and bring relief and maintaining the clearance for the long-run to reduce recurrence potential. Successful combinations are built on tolerability, ease of application, and the efficacy demonstrated by the synergy of the sum of the parts over being used separately.

J Drugs Dermatol. 2018;17(3):342-346.

Objective: To characterize the prevalence of psychiatric disorders in patients with moderate-to-severe psoriasis and compare health care costs between patients with and without psychiatric comorbidities.
Methods: In a retrospective, matched case-control study, data for services from nearly 75 health care plans in the United States (U.S.) were collected from PharMetrics Patient Centric Database using International Classification of Diseases, Ninth Revision Clinical Modification codes, identifying a total of 39,855 adults with moderate-to-severe psoriasis (n=7,971) and without (controls; n=31,884). Patients with psoriasis had at least one psoriasis health care claim and received at least one medical/prescription treatment claim within two consecutive years. Psychiatric comorbidities and treatments among patients and controls were determined by claims. Annual inpatient, outpatient, emergency room, and prescription costs for those with and without psoriasis and those with and without psychiatric disorders were compared.
Results: Patients had significantly higher prevalence of anxiety (6.9% versus 4.4%), depression (9.2% versus 5.3%), bipolar disorder (1.1% versus 0.5%), or delirium (0.3% versus 0.1%; P<0.05) than controls (others P<0.0001). Significantly higher proportions of patients with psoriasis received antidepressants (6.1% versus 0.9%), anxiolytics (5.0% versus 0.8%), or antipsychotics (5.9% versus 0.9%) compared with controls (each P<0.0001). Total health care costs for patients with psoriasis (US $11, 369.47) were significantly higher than for controls ($3,427.60; P<0.001). Psoriasis patients with psychiatric disorders had significantly higher health care costs ($17,637.66) than those without psychiatric disorders ($10,362.80; P<0.001).
Conclusion: The prevalence of psychiatric disorders is higher in patients with moderate-to-severe psoriasis than in controls. Annual health care costs are higher in psoriasis patients with psychiatric disorders than in those without psychiatric disorders.

J Drugs Dermatol. 2011;10(8):843-850.

Psoriasis may be frequently associated with psychiatric diseases. We present a 44-year-old man undergoing cyclosporine therapy for treatment of generalized plaque psoriasis which exacerbated his symptoms of paranoid schizophrenia, and disappeared a few days after discontinuation of cyclosporine. Replacement therapy with etanercept achieved clinical remission of psoriasis without any psychiatric side effects. Systemic medications, such as cyclosporine and etanercept, induce modifications of the cytokine network. This is pathogenetically significant in both psoriasis and psychiatric disorders. This case report suggests that dermatologists need to become more familiar with the risk-benefit of drug-induced cytokines dysregulation in psoriatic patients with comorbid psychiatric disorders.

The use of monoclonal antibodies against interleukin (IL)-12 and -23, such as ustekinumab, has considerably reduced the disease burden in many patients with moderate to severe psoriasis. Reversible posterior leukoencephalopathy syndrome (RPLS) is a neurologic disorder that has been documented with increased frequency with the use of systemic and biologic agents. We report a case of a 58-year-old man with psoriasis who presented with confusion and memory difficulties after being on treatment with ustekinumab for over six years. Imaging with CT and MRI revealed mild parenchymal edema with the typical appearance and distribution of RPLS, confirming the diagnosis of this condition. This case reports the second case of RPLS associated with ustekinumab treatment, with the only other known case reported during clinical trials. With the increasing use of biologics in patients with moderate to severe psoriasis, it is critical that clinicians are cognizant of this potential associated adverse event.

J Drugs Dermatol. 2017;16(2):177-179.

Background: Psoriasis is a chronic, inflammatory skin condition. The economic burden of psoriasis is approximately $35.2 billion in the United States per year, and treatment costs are increasing at a higher rate than general inflation. Light emitting diode (LED) phototherapy may represent a cost-effective, efficacious, safe, and portable treatment modality for psoriasis.

Objective: The goal of our manuscript is to review the published literature and provide evidence-based recommendations on LED phototherapy for the treatment of psoriasis.

Methods & Materials: A search of the databases Pubmed, EMBASE, Web of Science, and CINAHL was performed on April 5, 2016. Key search terms were related to psoriasis and LED-based therapies.

Results: A total of 7,793 articles were generated from the initial search and 5 original articles met inclusion criteria for our review. Grade of recommendation: B for LED-blue light. Grade of recommendation: C for LED-ultraviolet B, LED-red light, and combination LED-near-infrared and LED-red light.

Conclusion: We envision further characterizing the effects of LED phototherapy to treat psoriasis in patients may increase adoption of LED-based modalities and provide clinicians and patients with new therapeutic options that balance safety, efficacy, and cost.

J Drugs Dermatol. 2017;16(5):482-488.

Psoriasis rebound after efalizumab discontinuation is well-documented in the literature. We report the case of a patient who experienced psoriasis rebound 2 months after efalizumab discontinuation, despite being on more than 5 mg/kg/day of cyclosporine. This case illustrates an instance where high doses of a very efficacious antipsoriasis therapy were not sufficient to prevent efalizumab-associated rebound. In addition to describing this case, we also propose a theoretical mechanism to explain how rebound after efalizumab discontinuation comes about.

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European population. Over the last several years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. The goal of this article is to update the progress of the tumor necrosis inhibitors which are available, or under investigation, for clinical use in psoriasis: infliximab, etanercept, and adalimumab, as well as the T-cell-targeted therapies efalizumab and alefacept (Table 1).

BACKGROUND: The negative impact of psoriasis on health related quality of life (HRQoL) has been well documented. An unanswered question is the relative contribution of different manifestations of psoriasis (skin, joint, nail involvement) to HRQoL.
AIM: To assess the relative contribution of the different symptom domains on HRQoL in psoriasis.
METHODS: 165 psoriasis patients (41.2 % with psoriasis arthritis (PsA)) were enrolled in a single-center cohort-study. For the assessment of HRQoL, patients completed EuroQoL (EQ-5D), the Short Form 36-item Health Survey (SF-36), the Health Assessment Questionaire (HAQ), and Dermatological Life Quality Index (DLQI) questionnaires. Multiple regression analysis was applied to determine the contribution of the measured parameters to the EuroQoL score (used as a reference measure for overall HRQoL).
RESULTS: Psoriasis arthritis (PsA) patients showed a higher impairment in all HRQoL measures than the patients without PsA. PASI, number of affected joints (PsA-score), DLQI and HAQ were significant predictors of HRQoL (R2=0.57). HAQ was the dominant contributor to HRQoL, both in patients with PsA and without PsA (partial eta 0.23 and 0.28, respectively.) Final model with improved R2 (0.61) was obtained by backward regression analysis, and included 6 parameters: PASI, PsA-score, and three questions from HAQ and one question from DLQI questionnaire.
CONCLUSION: Musculoskeletal symptoms are an essential component of HRQoL in psoriasis, even in patients without active PsA. A model consisting of PASI, PsA-score, and 4 questions derived from DLQI and HAQ seems to reflect total HRQoL impairment in psoriasis. This finding may further optimize drug therapy in psoriasis.

J Drugs Dermatol. 2014;13(3):246-250.

The use of tumor necrosis factor alpha inhibitors (TNF-?) for psoriasis has raised greater awareness of tuberculosis screening. Tuberculosis can be acquired during foreign travel and also within the US by exposure to infected persons. We present a patient who converted to a positive purified protein derivative test (PPD) during anti-TNF-? treatment of psoriasis. PPD testing prior to any immunosuppressive treatment may be prudent, especially considering the benign nature and low cost of the test. As illustrated by this case, one may wish to consider annual tuberculosis testing for these patients.

The treatment options for psoriasis in HIV-infected individuals are limited due to the immunosuppressive nature of the therapeutic modalities and the patient's immunocompromised state. Etanercept has been shown to be safe and effective in the non-HIV psoriasis population with nearly 20 years of experience. However, there is limited data on the safety of etanercept use in the HIV patient population. The authors report a case of an HIV-infected patient with psoriasis who has remained mostly clear on continuous, uninterrupted etanercept use for over six years.

J Drugs Dermatol. 2012;11(3):413-414.

Plaque psoriasis is a chronic, inflammatory skin disease that can be difficult to treat. Traditional systemic agents, topical agents, phototherapy and biologic therapies can be used for patients with psoriasis. The authors reviewed published results from a variety of sources in order to better understand the effects of psoriasis treatments on patient satisfaction, patient adherence, healthcare resource utilization and productivity. Patients with psoriasis consider many factors when evaluating therapies, including the time for the therapy to be effective, cosmetic issues common with topical therapies and travel to and from phototherapy centers. Satisfaction with and adherence to biologic therapies appears to be greater than for traditional therapies. Although biologic therapies are generally more expensive than are traditional, these agents may contribute to decreased healthcare utilization and increased productivity.

J Drugs Dermatol. 2011;10(2):189-196.

Combination therapy for moderate to severe psoriasis is often used to enhance efficacy and minimize treatment-related side effects; however, data are limited on combination therapy with the newer biologic agents. The current study examined patients who received alefacept in combination with ultraviolet B phototherapy as part of an international, open-label study evaluating up to 3 courses of alefacept in combination with other psoriasis therapies. Physician Global Assessment (PGA) scores improved by 2 or more categories in 76% of patients and by 1 or more categories in 88% of patients in course A. Corresponding response rates were 100% and 55% in course B, and 85% and 77% in course C. At week 14, a PGA of “almost clear” or “clear” was achieved by 13%, 14%, and 8% of patients in courses A, B, and C, respectively. There was no evidence of a cumulative effect on T cells after multiple courses of therapy. The combination of alefacept and ultraviolet B was well tolerated and provided improvement in psoriasis.

BACKGROUND: Adherence to the treatment of psoriasis is poor and effects treatment outcomes. Literature on adherence to biologic therapy for the treatment of psoriasis is limited and difficult to measure. However, ustekinumab, which until recently was only approved to be administered in office, offers an opportunity to assess adherence through chart review.
PURPOSE: The purpose of this study is to determine adherence rates and reasons for nonadherence to ustekinumab in the treatment of psoriasis.
METHODS: This was a single center, retrospective study involving a chart review of patients with a diagnosis of psoriasis and administration of ustekinumab seen at one clinic between October 1, 2009 and June 1, 2013. We assessed the number of injections administered, the time between injections, and reasons for nonadherence.
RESULTS: 45 patients received ustekinumab for the treatment of psoriasis. The median time between doses of ustekinumab (n=164) was 13 weeks (91 days, interquartile range 89, 98). For patients that received at least 3 doses of ustekinumab, overall median adherence was 100% (IQR 66.7, 100). The median adherence to the 45 mg dose (n=26) was 100% (IQR 75, 100) and to the 90 mg dose (n=18) was 80% (IQR 60, 100; P=0.11).
LIMITATIONS: Only limited information was found on reasons for nonadherence. Conclusions: Adherence to ustekinumab in psoriasis patients appears to be higher than reported adherence rates to topical therapies and treatment with self-administered biologics. Many factors may contribute to the greater adherence.

J Drugs Dermatol. 2013;12(10):1090-1092.

BACKGROUND: Topical corticosteroids (TCS) are typically used for extended periods of time for chronic skin conditions, including psoriasis. Chronic TCS use may result in side effects similar to those of systemic corticosteroids. Patients may have subclinical adrenal suppression and be unaware of their risk in the case of serious trauma.
OBJECTIVE: The objective of this study was to investigate the real world effects of chronic TCS use and its effects on adrenal suppression in a chronic disease such as psoriasis.
MATERIALS: This retrospective study utilized data from screening visits of a psoriasis clinical trial in which subjects had been on chronic TCS.
RESULTS: In this study, subjects with moderate to severe psoriasis affecting 16-20% of total body surface area (BSA) and using high-potency TCS at screening had a lower post-cosyntropin cortisol level (18.83 mcg/dL) compared to those with moderate psoriasis involving 10-15% of total BSA and using lower potency TCS at screening (23.22 mcg/dL; P=0.03). Both subject groups had lower post-cosyntropin cortisol levels compared to normal, healthy adults (P<0.001 for both).
CONCLUSION: This suggests that real world chronic use of high potency TCS over a larger BSA may result in silent adrenal suppression.

J Drugs Dermatol. 2016;15(8):945-948.

We report a 67-year-old Caucasian man with a long-term history of recalcitrant plaque psoriasis and psoriatic arthritis who was initiated on a treatment regimen of apremilast and secukinumab after failing multiple topical, photo, and systemic therapies. This combination provided significant skin improvement with minimal drug side effects.

J Drugs Dermatol. 2016;15(5):648-649.

Introduction: Genital psoriasis is a common but frequently overlooked manifestation of psoriasis with a considerable impact on patients’ quality of life. Currently no validated clinical trial outcome measures exist to assess genital psoriasis severity that meet regulatory agency requirements.

Methods: This study describes the development of the static Physician’s Global Assessment of Genitalia (sPGA-G) scale, a clinical outcome measure for the assessment of genital psoriasis severity that accounts for the erythematous clinical presentation of genital psoriasis. The reliability of the sPGA-G was evaluated using scores collected from clinician assessments of photographs of genital psoriasis cases. Scores were collected from 10 academic and clinical experts in genital psoriasis and 95 clinician assessors who participated in either in-person (n=28) or online (n=67) sPGA-G training modules.

Results: The sPGA-G had a high inter-rater reliability (IRR, measured by Kendall’s W) for expert raters (W=0.856, P less than 0.0001), in-person assessors (W=0.822, P less than 0.0001), and online assessors (W=0.678, P less than 0.0001). IRR was also high for all clinical assessors combined, (W=0.714, P less than 0.0001).

Discussion: This study demonstrates that the sPGA-G is an intuitive and reliable clinical outcome measure that specifically measures the severity of genital psoriasis.

J Drugs Dermatol. 2017;16(8):793-799.

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Psoriasis is an immune-mediated cutaneous disease affecting 2% of the worldwide population. While topical therapy, phototherapy, oral systemic therapy, and biologic agents have been used, the treatment of psoriasis still remains a challenge. Ustekinumab is a biologic therapy that provides a novel avenue for management by blocking interleukin-12/23. The purpose of this article is to review the mechanism of action of ustekinumab and its efficacy in psoriatic patients. The use of ustekinumab in other immune-mediated diseases is also discussed. It is our goal to provide dermatologists with the knowledge to enable them to incorporate ustekinumab into their practice.

J Drugs Dermatol. 2013;12(3):317-320.

BACKGROUND: Combining narrowband UVB (NB-UVB) phototherapy with biologics has been shown to enhance the therapeutic response of plaque psoriasis patients. The objective of this study was to evaluate the effectiveness of apremilast combined with NB-UVB in patients with moderate to severe plaque psoriasis. METHODS: This was a 12-week, open-label study of 29 patients diagnosed with moderate to severe psoriasis. Patients received apremilast 30 mg twice daily, and increasing doses of NB-UVB (310-312 nm) 3 times per week for 12 weeks. RESULTS: Twenty-two of 29 patients (76%) completed the 12-week apremilast and NB-UVB combination therapy; 73% (16 of 22 completers) achieved a PASI 75 response at week 12. Mean scores for PASI, VAS pain, VAS itch, DLQI, and PGA improved by 77%, 77%, 69%, 70%, and 67%, respectively, at week 12. The most commonly reported adverse events (AEs) were mild and moderate first-degree burns related to NB-UVB (n=11 [38%] patients). A second-degree NB-UVB burn was reported (likely due to an underlying photosensitivity) and was considered a serious AE. CONCLUSION: The combination of apremilast with NB-UVB was effective for the treatment of moderate to severe plaque psoriasis, without any unexpected safety signals. Apremilast combined with NB-UVB provided a high treatment response in patients with moderate to severe plaque psoriasis, and may be an option for patients to enhance a patient’s initial therapeutic response.

J Drugs Dermatol. 2017;16(10):957-962.

Psoriasis is a chronic disease that exists in two phases: (1) the acute, flaring phase when psoriasis is highly inflamed, erythematous and pruritic and (2) the chronic, indolent phase after the acute manifestations are brought under control. Ideal therapies for psoriasis must focus on both of these phases. Therefore, a rapid and effective agent must be utilized to treat the acute phase, followed by safe long-term therapy for maintenance. This article proposes a new, effective sequential topical therapy for psoriasis using ongoing treatment with clobetasol (Clobex^®) spray for one month followed by calcitriol (Vectical^®) ointment for the next month. This strategy provides a highly effective, reliable and safe treatment option with minimal local and systemic adverse risks.

J Drugs Dermatol. 2011;10(8):831-834.

BACKGROUND: Psoriasis is a chronic disease that significantly impacts patients’ quality of life. It most commonly manifests as localized disease, for which there are various treatment options.
OBJECTIVE: To determine the prescription patterns of topical corticosteroids and vitamin D analogs for the treatment of psoriasis in the United States and how their use has changed over time.
METHODS: Data from the National Ambulatory Medical Care Survey (NAMCS) from 1994 to 2010 were queried for visits linked with a psoriasis diagnosis. Prescriptions for topical corticosteroids and vitamin D analogs were described. Vitamin D analogs usage was compared across physician specialties. For each sampled visit reported in the NAMCS, visits meeting our inclusion criteria that also mentioned the following medications were identified: topical calcipotriene, topical calcipotriene/betamethasone or any topical corticosteroid indicated for the treatment of psoriasis.
RESULTS: There were an estimated 2.05 million psoriasis visits per year over the 1994-2010 interval. Dermatologists were responsible for 67% of these encounters followed by family practice (14%) and internal medicine (11%). Dermatologists prescribed a vitamin D product at 15% of psoriasis visits, followed by family physicians at 12%, and internists at 5%. Dermatologists prescribed calcipotriene, calcipotriene/betamethasone, and topical corticosteroids in 15%, 4% and 59% of psoriasis visits, respectively. Over time, there was no significant change in the use of topical steroids or vitamin D products by physicians.This study is limited by the inability to determine the severity of psoriasis from the data collected, and the lack of data on the length of treatment with different medications.
CONCLUSIONS: Despite their demonstrated efficacy and safer side effect profile, vitamin D analogs are used less often than topical corticosteroids for the treatment of psoriasis. These findings suggest that vitamin D products may not be utilized to their fullest potential as effective topical therapy or adjuncts to therapy for localized plaque psoriasis.

J Drugs Dermatol. 2013;12(8):906-910.

Palmoplantar pustular psoriasis (PPP) is an uncommon form of chronic psoriasis. Characterized by sterile, intra-epidermal pustules located on the palms and soles, it is highly resistant to treatment. A patient presented with palmar inflammation and throbbing joint pain in his hands, as well as erythematous, pustular, and micaceous scaling skin on his right foot, legs, elbows and hands. Approximately 4% of his body surface area was involved, and he was diagnosed with PPP after skin biopsy. After conventional therapy failed, the patient underwent treatment with adalimumab and the majority of his symptoms resolved after 16 weeks of therapy. Adalimumab may be effective for the treatment of PPP. Adalimumab, a fully human, immunoglobulin G1 monoclonal antibody that binds to tumor necrosis factor, has been approved for the treatment of moderate-to-severe psoriasis, in the U.S., Europe and elsewhere.

Propylthiouracil (PTU), an antithyroid thioureylene with immunomodulatory properties, has been shown to be effective in the therapy of patients with plaque psoriasis. The mechanism of action of antithyroid thioureylenes in psoriasis remains unknown. Propylthiouracil is a commonly used agent in the treatment of patients with Graves’ hyperthyroidism, a condition associated with elevated levels of interleukin-12 (IL-12), which fall significantly after propylthiouracil treatment. IL-12 is believed to play a pivotal role in the development of psoriasis. Production of IL-12 is modulated by the anti-inflammatory cytokine IL-10. The effect of PTU on IL- 12 and IL-10 levels was, therefore, studied in twelve patients with plaque psoriasis. Treatment with 300 mg of PTU daily in divided doses for three months produced significant improvement of the PASI and histological scores in the patients. Serum IL-12 concentrations were undetectable at baseline and did not change with treatment. IL-10 concentrations were 1.39 ± 1.49 pg /ml (mean ± SD) at baseline, and showed no significant change after 2 weeks (1.63 ± 1.61 pg /ml and 12 weeks 1.15 ± 1.58 pg /ml of treatment with PTU. The data suggest that the clinical improvement with patients with psoriasis treated with PTU is not due to a fall in circulating IL-12 or a rise in IL-10 concentrations. Although the drug may have effects on lesional production of these cytokines this is not reflected in the circulating levels. It is speculated that the beneficial effect is likely mediated by an inhibitory effect on keratinocyte proliferation or promotion of apoptosis in these proliferated keratinocytes.

OBJECTIVE: To compare patients with psoriasis by cost level over 3 years.

METHODS: Psoriasis patients in a large US health plan in 2011-2013 were identified. Four groups were created by healthcare costs excluding biologics: patients having top 10% of costs in all 3 years (Top), top 10% in 2 of 3 years (High), bottom 90% in 2 of 3 years (Medium), and bottom 90% in all 3 years (Bottom). Comorbidities, utilization, and costs between groups were compared.

RESULTS: The study included 18,653 patients: 514 (3%), 805 (4%), 2,443 (13%), and 14,891 (80%) patients in the Top, High, Medium, and Bottom groups, respectively. Significantly more patients in the Top vs Bottom group had diabetes (31.1% vs 9.4%), cardiovascular disease (26.5% vs 4.3%), psoriatic arthritis (25.7% vs 10.7%), depression (27.8% vs 6.9%), and anxiety (22.0% vs 7.9%) in 2011 (all P less than 0.05). Patients in the Top group had more unique 2011 prescriptions (17.7 vs 6.6; P less than 0.001) than the Bottom group, but similar biologic use (22.4% vs 21.6%). Patients in the Top, High, Medium, and Bottom groups had mean 2011 total costs of $68,913, $40,575, $24,292, and $8,815, and contributed to 14%, 13%, 23%, and 51% of the overall costs, respectively. Mean total costs increased 14-18% over time for all groups. Although mean 2011 total costs for patients in the Top group were 7.8 times of those in the Bottom group, psoriasis-related costs were less disparate ($8,716 vs $4,541). Compared with patients in the Bottom group, those in the Top group were more likely to have any 2011 hospitalization (36.8% vs 2.6%; psoriasis-related: 11.1% vs 0.7%) or emergency visit (50.8% vs 20.8%; psoriasis-related: 3.9% vs 1.0%).

CONCLUSION: The costliest patients with psoriasis had significantly higher prevalence of comorbidities, prescription fills, inpatient and emergency utilization, but not biologic medication use or biologic costs.

J Drugs Dermatol. 2017;16(7):651-658.

There are several well-established guidelines for the treatment of psoriasis. Guidelines have been proposed in the United States by the American Academy of Dermatology (AAD), in Europe by the European S3, in the United Kingdom by the National Institute for Health and Care Excellence (NICE), and in Canada by the Canadian Dermatology Association. These guidelines are predominantly evidence-based, supported by expert panel consensus where evidence is lacking. Cyclosporine, a potent calcineurin inhibitor that acts selectively on T-cells, revolutionized the world of immunosuppression upon its discovery in 1970. Since its approval in 1997 by the U.S. Food and Drug Administration for the treatment of psoriasis, cyclosporine has been used with great efficacy in the treatment of not only psoriasis but also a wide consortium of dermatological diseases. However, in the past decade or so, many dermatologists have become increasingly hesitant to use this important drug because of its potent toxicity profile.
The purpose of this article is to review and compare the current evidence-based guideline recommendations for the use of cyclosporine in the treatment of psoriasis.
Although the various guidelines are similar in their initial treatment recommendations, significant differences exist in recommendations on maximal treatment duration (1 year versus 2 years), intermittent short-term versus continuous therapy, use in erythrodermic and palmoplantar psoriasis, as well as recommendations on managing cyclosporine-associated side effects. By following guideline recommendations, cyclosporine remains an excellent and indispensable tool for the dermatologist treating moderate-to-severe psoriasis.

J Drugs Dermatol. 2016;15(3):293-301.

Background: Clobetasol propionate is the most common topical therapy used for psoriasis in the US. Conventional dermatologic wisdom is that ointment preparations provide the highest potency (due to their occlusive nature and moisturizing ability) and are best suited for psoriasis. However, patients often find application of ointment to be messy, raising concerns about both short-term and long-term adherence to treatment. This article reviews the current literature and assesses the relative potency of clobetasol propionate ointment compared to other clobetasol propionate preparations in the treatment of psoriasis. Relevant literature was identified by PubMed and Google searches. We included studies of psoriasis that reported the percentage of subjects that achieved desired efficacy endpoints, as well as studies that reported the subjects’ mean change in symptoms from baseline. We excluded studies conducted before 1980 and those that allowed concomitant treatments. Observations: Efficacy rates ranged from 17% to 80% for the different vehicles: ointment, solution, foam, cream, lotion, shampoo, and emollient. Conclusions: Clobetasol propionate is a very effective treatment for psoriasis. Ointment preparations have similar efficacy to other preparations in clinical trial situations. In clinical practice, a situation in which patient preferences are more likely to affect compliance, it may be best to choose whichever vehicle patients find preferable.

Nail psoriasis can be debilitating and as therapeutic options are limited, it can be notoriously difficult to treat. As there are many new medications currently undergoing clinical trials in psoriasis, questions have arisen concerning the effectiveness of these new therapies with regard to psoriatic nail disease. We present the results of a prospective, open-label, proof of concept study to determine the efficacy and safety of alefacept in subjects with moderate to severe nail psoriasis.

Psoriasis affects approximately 2 percent of the population. Approximately 30–45 percent of those affected first experience symptoms during childhood or adolescence. Although biologics have proven to be a relatively safe and effective treatment option for adults with psoriasis, limited information is available regarding the use of biologic agents in pediatric patients with psoriasis. The authors attempt to assess and summarize the available data on the use of biologic agents in patients under the age of 18, regardless of the indication, as well as to examine the limited available data on the use of biologics for psoriasis in the pediatric population. In doing so, the authors aim to provide guidance on the safety and efficacy of biologic therapies in pediatric patients with psoriasis. The authors’ findings suggest that biologic agents should be considered for use solely in children with psoriasis that is refractory to conventional therapies, including children currently with severe, widespread, refractory pustular, plaque or psoriatic arthritis. Of all the currently available biologics, etanercept appears to have resulted in fewer and less severe side effects compared to infliximab in the juvenile rheumatoid arthritis population. In addition, while biologics are generally safe and effective in the pediatric population, serious adverse events (including infection), have been reported in the literature and should be taken into account before beginning treatment with any biologic agent. The physician and parents of the patient must carefully consider the risk-benefit ratio when deciding whether to use these medications. Additional randomized, controlled trials are needed to adequately assess the safety and efficacy of biologic medications for childhood psoriasis.

Background: There is a long history of using topical coal tar for the treatment of psoriasis and atopic dermatitis (AD). Objective: To review the literature on coal tar and its derivatives, without the use of ultraviolet light, for the treatment of psoriasis or AD. Methods: MEDLINE/PubMed and Cochrane Database of Systematic Reviews literature searches were performed to identify randomized controlled trials and clinical trials of topical coal tar for the treatment of psoriasis or AD. Studies were graded according to a modified version of Sackett’s criteria for clinical evidence and evaluated to determine if they support or do not support the use of coal tar therapy. Results: Twenty-five studies meeting the authors’ search criteria were identified, only two of which were placebo-controlled. The majority (21, or 84%) supported the use of coal tar products in the treatment of psoriasis or AD, while four (16%) did not support the use of coal tar products. Conclusion: Most studies support the use of coal tar products, although their level of evidence is not strong. Topical coal tar was found to be efficacious in the treatment of psoriasis in two placebo-controlled trials. Coal tar products appear to be therapeutic in psoriasis and AD, are well tolerated with few side effects, and are cost-effective. Staining and odor are deterrents to coal tar therapy. Large, randomized, double-blind, placebo-controlled studies with precise point estimates of treatment effect are needed to establish the efficacy of coal tar preparations.

BACKGROUND: Ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, has been established as safe and effective in 3 Phase 3 trials for the treatment of moderate to severe plaque psoriasis. The lifetime incidence of psoriatic nail disease is 80%-90% of patients, and approximately 50% of patients with psoriasis have nail involvement.
MATERIALS AND METHODS: The design of UNCOVER-3, a Phase 3, multicenter, double-blind, placebo- and active-controlled trial that evaluated the efficacy and safety of ixekizumab for moderate to severe psoriasis, has been published previously. Patients were randomized to receive blinded placebo, etanercept (50 mg twice weekly) or 80 mg ixekizumab every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) for 12 weeks. At week 12, all patients were assigned to open-label ixekizumab 80 mg every 4 weeks through week 60. In this 60-week post hoc subset analysis, we evaluated only those patients with significant baseline nail involvement, defined as fingernail NAPSI ≥16 and at least 4 fingernails involved.
RESULTS: Ixekizumab Q2W or Q4W resulted in greater improvement in nail psoriasis than placebo or etanercept by week 12 of administration, as measured by percent NAPSI reduction (IXEQ2W 39% improvement, IXEQ4W 40%, etanercept 28%, placebo -4.7%). At week 24, significantly more patients receiving ixekizumab exhibited no signs of nail involvement (IXEQ2W/Q4W 34%, IXEQ4W/Q4W 30%). Similar gains were observed at 60 weeks in all treatment groups.
CONCLUSION: Ixekizumab led to improvement in fingernail psoriasis by week 12 compared with placebo. Continued improvement in fingernail psoriasis with ixekizumab was observed, with >50% of patients achieving complete fingernail psoriasis resolution (NAPSI=0) at week 60.

J Drugs Dermatol. 2016;15(8):958-961.

The Koebner phenomenon refers to the development of lesions in response to injury of previously uninvolved skin. It occurs in psoriasis and a number of other inflammatory diseases. We present a patient who developed a Koebner reaction at the site of a tattoo. Treatment with ustekinumab resulted in striking clearance of the psoriasis changes at the tattoo site.

J Drugs Dermatol. 2011;10(10:1199-1200.

Psoriasis is a chronic inflammatory skin disease that affects millions of people in the United States as well as worldwide. While there is currently no cure for psoriasis, many treatment options are available. Topical therapies are the mainstay for the majority of patients who have limited or mild psoriasis. Among these medications, topical vitamin D analogs (eg, calcipotriene) and corticosteroids (eg, betamethasone), and these drugs in combination, are the most widely prescribed psoriasis drugs and are the cornerstone of topical therapies. For patients with more severe disease, phototherapy, conventional systemic agents, and biologics are often indicated. Currently, the goal of treatment is to control the clinical symptoms of the skin, reduce systemic disease potential, and improve the patient’s quality of life. Despite the availability of various therapeutic options for psoriasis, many patients go untreated, and even among those who are treated, many do not achieve complete resolution of the disease. The new consensus is to treat to a target of 1% or less of body surface area involvement. Innovative treatment strategies are needed to meet this goal and patients’ desire to achieve clear skin. Combination therapies are widely used by physicians, and adjunctive topical therapies used with other antipsoriatic regimens have been demonstrated to provide many clinical benefts. This article reviews the most recently published clinical evidence of adjunctive use of topical agents with biologics, conventional systemic agents, and phototherapy, to better establish the role of topical agents in combination therapy for the treatment of psoriasis.

J Drugs Dermatol. 2017;16(12):1209-1222.

Tumor necrosis factor alpha (TNF-?) inhibitors, such as infliximab, decrease the body’s inflammatory response and thus the body’s reaction to infection. Given the immune-mediated processes in psoriasis and psoriatic arthritis, patients with these disorders may benefit from infliximab therapy but may also suffer from an increased risk of infection. We present the first case of osteomyelitis in a patient receiving infliximab therapy for severe psoriasis and psoriatic arthritis. Infliximab and its serious adverse effects are discussed, and other cases of osteomyelitis with infliximab use are also reviewed.

Scalp psoriasis is a common life-altering skin condition causing a great deal of distress. It significantly affects quality of life and is difficult to manage. Treatment can provide variable results, often impacting patient compliance with therapy. Salicylic acid is used as adjunctive therapy to other topical treatments because of its marked keratolytic effect. Its effectiveness as a monotherapy is not fully understood. An emollient foam formulation of 6% salicylic acid (Salkera) in an ammonium lactate vehicle has recently become available. Efficacy, tolerability and patient acceptability of salicylic acid 6% emollient foam were assessed in an open-label pilot study of 10 subjects with scalp psoriasis. All psoriasis severity parameters were reduced with a significant decrease in Psoriasis Scalp Severity Index (PSSI) score from 15.3 to 3.0 after four weeks of monotherapy (P<0.001). Sixty percent of subjects were either "completely cleared" or “almost cleared” of their psoriasis. No adverse events (AEs) were reported. All signs and symptom tolerability measures demonstrated statistically significant score decreases with the exception of oiliness severity and patient-reported burning tolerability. Salicylic acid 6% emollient foam provides a useful option in the treatment of psoriasis that is highly effective, well tolerated and acceptable to patients.

J Drugs Dermatol. 2011;10(3):270-273.

Ustekinumab is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit shared by both the interleukin-12 and interleukin-23 cytokines. This study reviews clinical response and adverse events in 119 psoriasis patients who have received ustekinumab for a minimum of 1 year. The medical records of 119 psoriasis patients treated with ustekinumab at our referral clinic in Dallas between 2009 and 2013 were reviewed for response rates, side effects, and concomitant therapies. Of 119 patients, 117 (98%) had plaque type psoriasis, with 40 (34%) patients having psoriasis affecting either their palms and/or soles. Forty-four (37%) patients had psoriatic arthritis. The median follow-up period was 31 months. Fifty-six (47%) of the 119 patients obtained near complete clearance (response of more than 90% of initial body surface area involvement) upon the final follow-up visit or at the time of ustekinumab treatment discontinuation. Concomitant systemic treatments, primarily methotrexate, were given to 59 (50%) patients. Twenty-three (19%) patients discontinued treatment, primarily for sub-optimal response or loss of response. Fifty (42%) patients required either an increase in the dose of ustekinumab to 90 mg and/or administration more frequently than every 12 weeks to achieve and maintain psoriasis clearance.

J Drugs Dermatol. 2014;13(8):905-910.

Background: Combination therapy is a common and appropriate treatment strategy for moderate-to-severe psoriasis, as it provides for enhanced efficacy and decreased toxicity compared to the use of a single agent. Acitretin is an effective oral retinoid for psoriasis that seems to find its greatest value when complemented by other topical and systemic treatments.
Objective: The primary aim of this study is to assess the use of acitretin in combination with other treatments for psoriasis.
Methods: We assessed the use of acitretin for the treatment of psoriasis using nationally representative survey data from the National Ambulatory Medical Care Survey (NAMCS).
Results: Among visits where acitretin was listed in the NAMCS, other psoriasis medications were co-prescribed in 62 percent of visits. The co-prescribed medications included topical corticosteroids (51%), calcipotriene (31%), biologics (6%), cyclosporine (5%), methotrexate (5%) and tazarotene (2%).
Conclusion: The use of acitretin in combination with other psoriasis treatments, particularly topical corticosteroids and calcipotriene, is a common practice. Acitretin is co-prescribed with the biologics, likely because of the relative lack of overlapping effects on immune function. The immune-sparing method of action of acitretin makes combination treatment with the systemic agents an attractive treatment option, especially in patients where further immunosuppression is unwarranted.

J Drugs Dermatol. 2011;10(8):876-880.

Psoriasis is a common, chronic immune-mediated inflammatory skin disorder that significantly impacts quality of life and has potential systemic complications. The majority of psoriatic patients have mild to moderate disease and are adequately controlled with topical medications. However, approximately 20% of patients have moderate-to-severe disease. Phototherapy has remained a mainstay option for patients with moderate-to-severe psoriasis resistant to topical treatments due to its efficacy, cost-effectiveness, and relative lack of side effects, in particular a lack of systemic immunosuppression seen with traditional and biologic systemic therapies. There are several well-established guidelines for phototherapy treatment of psoriasis proposed in the United States by the American Academy of Dermatology (AAD), in Europe by the European S3, and in the United Kingdom by the National Institute for Health and Care Excellence (NICE). The guidelines set by these groups are largely based on current evidence or expert panel consensus where evidence is lacking. This article reviews and compares the current recommendations of these guidelines for psoriasis phototherapy in regards to the initial clinical encounter, dosage, adverse reactions, and special considerations.

J Drugs Dermatol. 2016;15(8):995-1000.

BACKGROUND: To assess baseline knowledge and awareness of cardiometabolic comorbidities in subjects with psoriasis. To determine the impact of a verbal scripted educational intervention. METHODS: Fifty-six adults with a clinical diagnosis of moderate to severe psoriasis completed a 12-item questionnaire about psoriasis comorbidity awareness and knowledge at 2 time points: pre-intervention (PR-I) and post-intervention (PO-I). The PR-I questionnaire collected information on history of psoriasis and cardiometabolic disease. A 5-minute scripted educational intervention was administered during a single study visit to subjects immediately after PR-I but prior to PO-I questionnaires. Subjects also completed a final questionnaire at 2 months follow-up (2-MF). Responses were statistically analyzed using McNemar’s test. RESULTS: Fifty-six subjects (26 females, 30 males, mean age 51 years, range 21 to 83 years) participated in the PR-I and PO-I and 46 (82%) participated in 2-MF. Significant improvements were noted for 10 of 11 questions between PR-I and PO-I, and 8 of the scores remained significantly improved (compared with baseline) at 2-MF (P<0.05). At 2-MF, 65% of subjects had seen a primary care physician within the 2-month interval from PO-I to 2-MF, and another 26% planned to visit a primary care physician in the near future. Furthermore, 85% had checked their blood pressure in the past 2 months. CONCLUSIONS: Measures of knowledge and awareness of psoriasis and cardiometabolic comorbidities were significantly improved at PO-I and retained for most measures at 2-MF. An educational intervention, as utilized in this study, warrants consideration to enhance cardiometabolic-based knowledge and awareness in patients with psoriasis.

J Drugs Dermatol. 2016;15(10):1176-1180.

BACKGROUND/PURPOSE: No systemic drugs are approved by the Food and Drug Administration to treat pediatric psoriasis due to a lack of supporting data. The purpose of this study is to present cases demonstrating the use of systemic drugs in pediatric psoriasis.
METHODS: In this case series, data were collected on patients ≤ 18 years old with moderate-to-severe psoriasis treated with systemic medications (traditional systemic drugs or biologics) from 2008 through 2014. Efficacy was measured using the validated simple measure for assessing psoriasis activity (S-MAPA), and the product of the body surface area and Physician Global Assessment.
RESULTS: Twenty-seven patients aged 5 to 18 years were eligible, and 56 treatment courses were analyzed. Methotrexate (MTX) was the most frequently prescribed systemic (70%), followed by etanercept (59%). Clearance rates were highest on biologic medications (67% for etanercept and adalimumab, 33% for ustekinumab). Phototherapy, cyclosporine, and MTX were less effective in clearing psoriasis, although they were successful in improving S-MAPA ≥ 50% from baseline 100%, 67%, and 36% of the time, respectively. The most common adverse events were sunburn for patients on narrowband ultraviolet B phototherapy (14%), gastrointestinal intolerance and minor infections for patients on MTX (16% each), and minor infections for patients on etanercept (25%) and adalimumab (33%). The most common reasons for discontinuation were secondary failure (38% for etanercept, 33% for adalimumab) or lack of response (37% for MTX, 33% for cyclosporine).
CONCLUSION: Although phototherapy, MTX, and cyclosporine are effective for controlling resistant pediatric psoriasis, concerns about long-term safety or inconvenience have led people to consider biologics in their place. However, there is a lack of literature on the use of biologics in pediatric psoriasis. These cases attest to the safety and efficacy of etanercept, adalimumab, and ustekinumab in pediatric psoriasis, expanding the treatment repertoire and guiding dermatologists in better managing recalcitrant pediatric psoriasis.

J Drugs Dermatol. 2015;14(8):881-886.

BACKGROUND: Psoriasis is treated with several classes of treatments that may be used in combination, but the ways combination therapies are used are not well characterized.
PURPOSE: To determine the frequency of prescribing calcipotriene and other psoriasis drugs in combination.
METHODS: Visits with a sole diagnosis of psoriasis were selected from 1990-2010 data from the National Ambulatory Medical Care Survey. The number of combination therapies used, the leading therapies in each class of medications, and the leading types used in combination were analyzed.
RESULTS: About 10.2 million of 20.3 million psoriasis visits used multiple treatments. The mean number of prescribed medications increased over time (P=.0003). The top 10 treatments included 6 topical steroids, calcipotriene, 2 other topicals, and methotrexate. The most common combinations were topical steroid plus other topical (15.0%), multiple topical steroids (11.5%), topical steroid plus vitamin D analogue (9.7%), and topical steroid plus systemic treatment (6.9%). Vitamin D analogues and systemic treatments were prescribed with increasing frequency over time, while fewer topical steroids were used, and use of other topicals did not change significantly.
LIMITATIONS: Visits with multiple diagnoses had to be excluded to ensure that the medications listed were for psoriasis.
CONCLUSIONS: Combination therapy is the most common way to treat psoriasis in the United States. The wide range of combination therapies prescribed may reflect increased attention to individualization of treatment to match patients’ diverse preferences.

J Drugs Dermatol. 2013;12(5):546-550.

Background:Although major advances in the understanding of its pathogenesis have been achieved, psoriasis remains an incurable disease. In April 2004, etanercept, an antagonist of TNF-?, was approved by the Food and Drug Administration for the treatment of chronic, moderate to severe plaque psoriasis in adults. In this study we intend to document the efficacy and further establish the safety profile of etanercept for the treatment of moderate to severe psoriasis in our population and compare our data to the Leonardi et al study published in 2003.2 Methods: A total of 26 patients were followed for a period of 24 weeks. Subjects were administered 25 mg of etanercept subcutaneously twice weekly for 24 weeks. Patients were seen every 4 weeks to measure clinical improvement by means of the psoriasis area and severity index (PASI) scores. Development of side effects was also assessed. Results: Ninety-two percent of the patients had an improvement of greater than 50% in their PASI score, with 79% of these patients with a PASI improvement of 75% or greater. Adverse events were uncommon and none required the permanent discontinuation of treatment. Conclusion: Treatment with etanercept was well-tolerated and resulted in significant sustained improvement of psoriasis throughout a period of 24 weeks. Our data stronger correlates with the findings reported by Leonardi et al in 2003.

Background: Use of coal tar with narrowband (NB) ultraviolet B (UVB) light (the Goeckerman regimen) is an effective treatment for plaque psoriasis that has become impractical in outpatient care mainly due to the inconvenience and aesthetic concerns of coal tar.
Objective: This study evaluated the safety, efficacy, and convenience of adding a novel LCD (coal tar) solution to standard NB-UVB phototherapy in adults with chronic plaque psoriasis.
Methods: Patients applied LCD solution to half-body twice daily at home and received outpatient full-body NB-UVB light therapy 3 times a week for up to 12 weeks. A blinded investigator graded psoriasis severity of body halves and bilateral target lesions and monitored adverse reactions. Patients rated their psoriasis symptoms and LCD solution aesthetics.
Results: NB-UVB + LCD therapy reduced the median time to clearance or minimal disease in at least 50% of the population by 3 weeks (4 weeks with NB-UVB + LCD versus 7 weeks with NB-UVB alone). A statistically superior clinical response was observed by the end of week 4 with NB-UVB + LCD versus NB-UVB alone (P < 0.05) for: PGA, target lesions, ESI scores, and patient-reported symptoms.
Conclusion: Incorporating an at-home regimen with a novel LCD solution into outpatient NB-UVB light therapy is safe, convenient, effective, and can improve psoriasis more quickly than NB-UVB light therapy alone.

Psoriasis is a complex, multigenic immune/inflammatory-mediated disorder that variably affects the skin, nails, and joints. In September 2009, ustekinumab (Stelara®), a monoclonal antibody that targets interleukin 12 (IL-12) and 23 (IL-23), was approved in the United States for treatment of moderate-to-severe plaque psoriasis. The drug's mechanism of action is derived from extensive immunologic and genomic research identifying IL-12 and IL-23 of the Th1 and Th17 inflammatory pathways, respectively, as key mediators of psoriasis. Ustekinumab is a completely human monoclonal antibody to the shared p40 subunit of IL-12 and IL-23. The drug has demonstrated efficacy, short-term safety, and convenience of use in the treatment of plaque psoriasis and psoriatic arthritis. Though long-term safety concerns remain, ustekinumab adds to the current treatment armamentarium and holds promise to improve quality of life. This is a concise and current review of ustekinumab in the treatment of plaque psoriasis and psoriatic arthritis, with focus on data from the seven published clinical trials.

J Drugs Dermatol. 2012;11(2):160-167.

We herein report a case of psoriasis verrucosa that was successfully treated with adalimumab. A 55-year-old Japanese male had a five-year history of psoriasis vulgaris treated with topical agents. His past history included atypical psychosis treated with lithium carbonate and obesity. Despite treatment, verrucous scales developed on erythematous plaque. After treatment with adalimumab, these improved remarkably, and the patient's Psoriasis Area and Severity Index score decreased from 16.2 to 3.7.

J Drugs Dermatol. 2012;11(11)e74-e75.

BACKGROUND: Moderate-to-severe psoriasis generally requires systemic therapy, and is often undertreated.
OBJECTIVE: To determine and analyze what courses of treatment and in what frequency are being utilized to combat psoriasis in the United States.
METHODS: Analysis of data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) of the National Center for Health Statistics. Data were analyzed to examine the prevalence of different therapy techniques to combat psoriasis from 1993 through 2010. The trends for phototherapy, methotrexate (MTX), retinoids, cyclosporine A (CSA), systemic steroids, and biologics were all analyzed over the entire 18-year period and independently before and after the introduction of biologics in 2002.
RESULTS: From 1993 to 2010, the trend for total systemic treatments has not significantly increased (P=0.5). Frequency of phototherapy treatments significantly decreased from 1993 to 2010 (P<0.001). Since the introduction of biologics in 2002, their frequency has significantly increased, becoming the most frequently used treatment from 2008-2010 (P<0.0001).
LIMITATIONS: Severity of psoriasis was not recorded in the NAMCS and NHAMCS.
CONCLUSIONS: The frequency of systemic treatments to treat psoriasis has not significantly increased from 1993 to 2010. Despite the introduction of biologics, it appears that little progress has been made in reducing under-treatment of moderate-to-severe psoriasis.

J Drugs Dermatol. 2014;13(8):917-920.

Eleven patients with well-controlled psoriasis on cyclosporine (Physician’s Global Assessment [PGA] of “mild” or better) participated in an open-label study that evaluated a strategy for transition to alefacept. Using this transition strategy, 7 of 11 patients (64%) maintained PGA scores. Quality of life improved or was maintained in all patients. Adverse events and reductions in CD4+ T cell counts were consistent with those seen during alefacept monotherapy.

Inverse or intertriginous psoriasis commonly involves skin fold areas including the axillae, perianal skin, intergluteal cleft, inframammary, genital/inguinal, abdominal, and retroauricular folds. After reviewing the literature for new treatments, a task force was convened to update a consensus on inverse psoriasis therapy. Short-term treatment continues to be low-potency topical steroids. In order to avoid steroid-induced adverse effects, long-term therapy includes topical immunomodulators, calcitriol, and calcipotriene. Second and third-line therapies include antimicrobials, emollients, and tar-based products. Inverse psoriasis resistant to topical therapy has been shown to respond to botulinum toxin injections, excimer laser therapy, and certain systemic agents (such as anti-TNF and anti-IL12/IL23 therapy). Based on promising results from case reports and prior clinical experience, these systemic agents should be strongly considered in inverse psoriasis resistant to topical therapy. However, they need further evidence-based evaluation. The use of randomized trials and objective severity indices may allow for more robust therapeutic data.

J Drugs Dermatol. 2017;16(8):760-766.

While burden of disease (BOD) data exists for plaque psoriasis, and to a lesser extent other phenotypes of psoriasis, there is no published data on the impact of inverse (intertriginous) psoriasis. We sought to assess the overall BOD among patients with inverse psoriasis (IP). We introduce the Inverse Psoriasis Burden of Disease (IPBOD) questionnaire and compare it to the Dermatology Life Quality Index (DLQI). In this cross-sectional pilot study, we administered the IPBOD and the DLQI to 16 patients. We present the initial psychometric properties of the IPBOD survey. We used Spearman’s correlation coefficients to compare the two questionnaires on overall performance and in specific domains. Our cohort had an average age of 55.6 (SD 16.6) years, was predominantly female (68.8%), and white (87.5%). 87.5% of patients had a second psoriasis subtype. A majority of patients reported some effect of IP on pain (n=14, 87.5%). Thirteen (81.3%) patients reported some effect on depressed mood or anxiety/worry. Overall, the largest effect was on body self-image (93.8% reporting an effect). The average DLQI score was 8.5/30, higher than average DLQI scores reported in patients with plaque psoriasis or psoriatic arthritis. Average IPBOD score was 4.9/10. The reliability of IPBOD was good (overall Cronbach’s alpha = 0.89, individual items’ range 0.88 – 0.91). Correlations between IPBOD and DLQI were: overall (Spearman’s P=0.650, P=0.006), symptoms (P=0.462, P=0.072), daily activities (P=0.507, P=0.045), leisure (P=0.633, P=0.008), interpersonal function (P=0.728, P=0.001), and work and school (P=0.427, P=0.100). IP has a profound impact on patients’ lives and the results of this pilot study suggest that the IPBOD questionnaire may be a useful disease-specific tool for measuring the BOD of IP.

J Drugs Dermatol. 2016;15(8):1011-1016.

Adult patients with psoriasis have an increased prevalence of the metabolic syndrome (MetS) and cardiovascular disease (CVD) risk factors due to elevations of Tumor Necrosis Factor and other inflammatory cytokines.^1,2 Recently, higher rates of hyperlipidemia, obesity, hypertension, and diabetes mellitus were seen in patients with juvenile psoriasis.³ Here, we report the interim results of an ongoing study of MetS and CVD risk factors in pediatric psoriasis patients.

J Drugs Dermatol. 2011;10(8):903-904.

Background: Inflammatory cytokines play a crucial role in the pathophysiology of psoriasis. New therapies are targeting Janus kinases (JAKs), enzymes involved with transduction of cytokine receptor signaling.
Objective: Review the utility of JAK inhibitors in the treatment of psoriasis.
Methods: A review was performed using PubMed and Google to identify research relevant to the treatment of psoriasis using JAK inhibitors.
Results: In a CD18 mutant PL/J mouse model with T-cell dependent psoriasiform skin disease, the JAK inhibitor R348 reduced skin inflammation, with reductions in CD4+, CD8+, and CD25+ T-cell infiltration and systemic decreases of IL-17, IL-19, IL-22, IL-23 and TNF-α. Two JAK inhibitors, CP-690,550 (tasocitinib) and INCB018424 (ruxolitinib), were effective in psoriasis clinical trials. In a phase 1, randomized, double-blind, dose escalation trial for plaque psoriasis, CP-690,050 led to improvements in Psoriatic Lesion Severity Sum score at doses greater than 5 mg. A phase 2 trial showed CP-690,050 administered at 2, 5, and 15 mg twice daily resulted in a 75% reduction in Psoriasis Area and Severity Index (PASI) in 25%, 40.8%, and 66.7% of patients, respectively, for moderate to severe psoriasis. A phase 3 study of CP-690,550 for plaque psoriasis was begun in September 2010 (NCT01163253). INCB018424, another JAK inhibitor, was used topically at 3 doses (0.5%, 1%, 1.5%) in a phase 2B, double-blind, placebo-controlled trial, resulting in improved total lesion score, global assessment, and PASI for all doses.
Conclusion: Janus Kinase inhibitors are promising potential therapeutic options for psoriasis.

J Drugs Dermatol. 2012;11(8):913-918.

For nearly 5 decades, methotrexate has been the backbone of moderate-to-severe psoriasis treatment. The benefits of methotrexate therapy include reliable efficacy, low cost, relative ease of administration, and its usefulness as part of combination therapy regimens, making it a drug of choice for treating psoriasis. While methotrexate can be administered orally, intravenously, or intramuscularly, the self-administered subcutaneous use of the drug is the most advantageous route. Subcutaneous methotrexate is associated with fewer adverse events and higher absorption rates, accompanied by bioavailability that is both linear and predictable throughout the range of possible doses. In addition, the subcutaneous route, when compared with oral administration, facilitates improved efficacy by promoting higher intracellular levels of long-chain methotrexate polyglutamates. Taken together, these features allow patients the highest probability of a successful therapeutic experience. Subcutaneous methotrexate should be considered a viable option for the appropriate patient with moderate-to-severe psoriasis.

J Drugs Dermatol. 2014;13(8):929-931.

Psoriasis is a chronic inflammatory skin disease that is characterized by thickened red plaques covered with silvery scales. Excimer laser therapy is a cutting-edge advancement in UVB phototherapy. In contrast to traditional phototherapy, the 308 nm excimer laser only targets psoriasis plaques, while it spares uninvolved skin. It allows for treatment with a supra-erythmogenic dose of UVB irradiation. Targeted UVB therapy is a possible treatment especially for many who have failed topical treatments, systemic therapy, and traditional phototherapy. For safe and effective psoriasis treatment, a combination of therapies may be used, including a combination of laser treatment with topical medications. We present two cases demonstrating effective treatment with excimer laser in conjunction with clobetasol spray and calcitriol ointment for 12 weeks. Long-term near-clearance of psoriasis was sustained after 6 months and one-year follow up periods without further therapy.

J Drugs Dermatol. 2012;11(8):994-996.

Tacrolimus is an immunosuppressive drug that has proved effective in the treatment of psoriasis when administered systemically. Topically, it seems only useful in thin psoriasis plaques located on the face, genitalia, and intertriginous areas. We present an open-label clinical trial to test the efficacy of 0.1 % tacrolimus ointment in patients with psoriasis on the face, intertriginous areas, both, and in corporal plaques. Efficacy was assessed with the evaluation of erythema, desquamation, infiltration, reduction of the PASI, and reduction of itching. A total of 15 patients were enrolled in the study. In all the localizations evaluated, each of the signs (erythema, desquamation, and infiltration) showed a statistically significant improvement when compared to the baseline (p<.001). Itching also improved rapidly. PASI was also reduced from a mean of 12 at baseline to 2.2 at the end of the study. Of the 15 patients, only 2 experienced an adverse effect (13%), which was described as a warm sensation in facial lesions which was transient and self-limited. In conclusion, tacrolimus ointment may be an alternative to classical options for the treatment of psoriasis, not only for intertriginous, genital, and facial areas, but also for corporal plaques without occlusion, with good tolerance.

A combination of multiple agents is often required to achieve treatment success for plaque-type psoriasis. We report a case series of 10 patients that were treated with betamethasone valerate foam (0.12%) in the morning and topical tazarotene cream (0.1%) in the evening for a total of 12 weeks or until plaques cleared. Erythema, scale, and thickness along with an aggregate severity score were determined at weeks 4, 8, and 12. One patient was lost to follow-up. Eight of the other 9 patients experienced improvement in their disease by week 12. Two patients were clear of their psoriasis at week 4 and 4 were clear at week 8. No adverse events, including irritation were reported; the use of the corticosteroid foam may protect against potential local irritation reported with tazarotene. The combination of tazarotene cream and betamethasone valerate foam is an effective combination approach to treating localized plaque-type psoriasis

Scalp Psoriasis, How and When to Use Biologics in Psoriasis, Enhancing the Eyes: Use of Minimally Invasive Techniques for Periorbital Rejuvenation, and Facial Shaping: Beyond Lines and Folds With Fillers

Background: Psoriasis of the skin is in itself a disturbing disorder both physically and psychologically. However, most often the scaly plaques can be hidden by clothing. When psoriasis involves the face it can be more disabling and can decrease the patient’s quality of life. Facial psoriasis is difficult to treat and is associated with severe cutaneous disease. Patients who have a long duration of psoriasis or early age of onset are more likely to suffer from facial involvement. Facial psoriasis may also be associated with pruritus, psoriatic arthritis, and with a family history of psoriasis.
Objective: The authors report a case of a female patient with psoriasis with severe cutaneous disease and extensive facial involvement successfully treated with adalimumab. This 50-year-old Caucasian female had a history of cutaneous psoriasis since 1990 and psoriatic arthritis since 2005. The patient had associated pruritus and a family history (maternal). Systematic treatment with mycophenolate mofetil and acitretin proved unsuccessful. The patient also lost efficacy after months of ultraviolet light B and topical psoralen plus ultraviolet light A phototherapy.
Results: In 2007, the patient was screened and initiated therapy with a monoclonal humanized tumor necrosis factor alpha inhibitor, adalimumab. She had severe facial and body involvement with a body surface area of 25%, a Psoriasis Area and Severity Index of 20.4 (PASI), and a head and neck psoriasis area and severity index (HNPASI) of 3.6. Photographic documentation was carried out with improvement noted as soon as 4 weeks with continuing significant response thereafter. No adverse effects were noted. The patient’s quality of life also improved.
Limitations: Although severe facial psoriasis is rare and associated with only the most extensive and severe psoriatic cases, it is likely the most psychologically disturbing and cosmetically disrupting to the patient because it cannot easily be covered or concealed. The authors hope this case can illustrate an excellent therapeutic option for these patients.
Conclusion: Although facial psoriasis is difficult to treat, with newer systemic therapy now available in the form of biologics, patients now have a hope for this disease, especially devastating when associated with severe and extensive cutaneous involvement. The case gives promise in a serial photo-documented fashion of the success that can be achieved.

The association between guttate psoriasis and pityriasis rosea with Streptococcus pyogenes (S. pyogenes) is well established in the literature; however treatment guidelines and necessity have not been clarified with respect to the infectious etiology. Also, the exact role of Streptococcus in the immunopathogenesis of these entities, and the associated risk of development of scarlet fever and poststreptococcal sequelae, are not centrally reported. No single report or case series definitively establishes the coexistence between guttate psoriasis and post-streptococcal sequelae in the same patient, supporting the theories of autoimmune protection conferred between these entities. Laboratory investigations and treatment of Streptococcus in the setting of guttate psoriasis are not necessary, as anti-streptococcal treatment does not significantly modify the course of cutaneous disease, and there is no theoretical or documented risk of post-streptococcal sequelae. However, due to minimal data, antibiotics may still have a role in pityriasis rosea.

Background: Psoriasis is among the top dermatologic diagnoses for older adult patients, and the number of older adult psoriasis patients is expected to rise.
Purpose: To characterize trends in older adult psoriasis health care practices of US ambulatory physician offices from 1993 to 2009.
Methods: We used data from the National Ambulatory Medical Care Survey to assess demographics, specialties seen, and treatment in visits by older adult patients, 55 years of age and older.
Results: There were approximately 14.1 million outpatient visits for psoriasis among the older adult population during the study period. Older adult psoriasis patients were 52.4% female and 47.6% male. The most frequent older adult age group seen for psoriasis was the 55 to 64 year age group. Dermatologists saw 69.3% of patients, internists saw 14.5%, and general and family practitioners saw 11.6%. Topical corticosteroids were the most frequently prescribed medications. Dermatologists preferred clobetasol whereas non-dermatologists more commonly prescribed betamethasone. For both the 18 to 54 year age group and the 55 and older group, the leading 7 out of 10 medications prescribed were topical corticosteroids and calcipotriene. However, etanercept, coal tar, and fluocinolone were among the leading medications in the younger group but not in the 55 and older group.
Conclusions: Treatment approach for older adult psoriasis patients showed some differences among medical specialties and among the younger and older age groups. Further research specific to older adult psoriasis patients is needed to determine optimal treatment strategies for this patient population.

J Drugs Dermatol. 2012;11(8):957-962.

Cyclosporine has been shown to increase the risk of lymphoma when used in organ transplant patients; however, studies have failed to demonstrate an increased risk of lymphoma when used at lower dermatologic doses for psoriasis. The authors present a case of solid B-cell lymphoma occurring in a psoriasis patient with a history of intermittent exposure to high-dose methotrexate, followed by low-dose cyclosporine for two years and subsequently transitioned to treatment with adalimumab. Methotrexate, cyclosporine and adalimumab are each effective treatments for psoriasis. However, when faced with an interplay of several factors, closer surveillance for malignancy is warranted than that which is currently considered for monotherapy.

Nail psoriasis appears to be an important source of psoriatic morbidity through physical impairment, pain, and cosmetic disturbances. Conventional treatment is often unsatisfactory. A systematic review of studies reporting the effect of TNF-α inhibitors and related drugs on nail psoriasis using the Nail Psoriasis Severity Index (NAPSI) as the outcome measure was therefore made. Data are available from randomized controlled trials (RCT) where NAPSI has been studied as a secondary outcome, as well as from case-series in which NAPSI has been the primary outcome studies suggest that adalimumab, briakinumab, etanercept, golimumab, infliximumab, and ustekinumab all improve NAPSI scores. No direct comparative RCTs are available in which NAPSI scores have been reported. The data further suggest that changes in NAPSI mirror changes in disease severity of other psoriatic manifestations, that is, in psoriatic arthritis and skin psoriasis. The effect only appears to be delayed due to the rate of growth of the nail plate.

J Drugs Dermatol. 2012;11(8):939-942.

Epigenetic phenomena, including DNA methylation, histone modification, and genetic regulation by miRNAs, are potentially heritable genetic regulatory changes that are not attributed to direct alterations in the DNA sequence of base pairs. They may explain the link between psoriasis risk alleles and disease development, as alleles possess various potentials to undergo epigenetic modification. Multiple genes involved in psoriasis pathogenesis demonstrate abnormal methylation patterns including those involved in epidermal differentiation and proliferation, immunity, the cell cycle, apoptosis, inflammation, and IFN-γ and TNF-α signaling. Hypoacetylation of histone H4 is observed in peripheral blood mononuclear cells of psoriatic patients, and the degree of hypoacetylation of histone H4 is inversely correlated to the PASI score. Investigators have reported both increased and decreased expression of miRNAs in patients with psoriasis, and have described and speculated a number of possible mechanisms for their roles in pathogenesis. Interestingly, the altered methylation patterns observed in psoriasis appear to be normalized by treatment with biologics directed at TNF-α inhibition. However, attempts to directly correlate epigenetic regulatory mechanisms with expression of genes observed in psoriasis have been limited thus far, and correlating miRNA expression levels to disease phenotypes can be challenging and inconsistent. Hopefully, the goal of drawing clinically relevant conclusions about the role of epigenetics in psoriasis will be aided by recent methods that enable fast and sensitive epigenomic profiling. Drugs targeting epigenetic mechanisms are currently being explored, though not for psoriasis, but specificity to pathogenetic mechanisms remains elusive. However, the amenability of cutaneous disease to topical therapies may elevate their usefulness in the treatment of this common skin disorder.

J Drugs Dermatol. 2014;13(2):111-118.

BACKGROUND: Among patients with moderate-to-severe psoriasis, efficacy, and tolerability of available treatments based on psoriatic arthritis (PsA) history are not well-described.
OBJECTIVE: We evaluate disease characteristics and treatment response variation in the moderate-to-severe psoriasis population based on PsA history.
METHODS: Simple-measure for assessing psoriasis activity (S-MAPA) was used to retrospectively analyze treatment responses.
RESULTS: 191 moderate-to-severe psoriatic patients, 58 with and 133 without rheumatologist-diagnosed PsA were analyzed. Regardless of PsA history, S-MAPA improvement was similar with biologic monotherapy (46.2 versus 44.1; P=0.74), traditional systemic monotherapy (62.29 versus 38.12; P=0.22), and combination treatments (64.62 versus 52.71; P=0.40) after 12 weeks. PsA patients on biologic monotherapy experienced a higher infection rate than patients without PsA (0.57% versus 0.19%; P=0.01). PsA patients experienced more adverse events (AEs) associated with traditional systemic monotherapy than biologic monotherapy (3.25 versus 1.04; P=.001).
LIMITATIONS: The relatively small PsA cohort was the primary limitation.
CONCLUSIONS: Patients with moderate-to-severe psoriasis responded similarly to all treatments independent of PsA history. PsA patients received more overall treatments and more biologic monotherapy prescriptions. PsA patients had a greater infection risk on biologic monotherapy compared to those without PsA, and greater adverse events risk on traditional systemic monotherapy compared to biologic monotherapy.

J Drugs Dermatol. 2016;15(8):917-922.

BACKGROUND: A novel formulation of 0.05% betamethasone dipropionate in an emollient spray vehicle (DFD-01) was developed to deliver steroid to the skin layers most affected by psoriasis.
OBJECTIVE: To compare the efficacy and safety of DFD-01 to its vehicle for the treatment of moderate plaque psoriasis over 4 weeks.
METHODS: Two Phase 3 trials enrolled adults with moderate psoriasis (Investigator Global Assessment [IGA]=3; 10–20% body surface area [BSA]) and randomized them 2:1 to DFD-01 or Vehicle. Products were applied twice daily to affected areas for 28 days. Treatment success was defined as an IGA=0 or 1 and ≥2-grade improvement from baseline. Primary endpoint was the proportion of subjects achieving treatment success at day 15.
RESULTS: Moderate psoriasis subjects were enrolled in Study 1 (174 DFD-01; 87 Vehicle) and Study 2 (182 DFD-01; 95 Vehicle). Mean BSA was 13–14%. Treatment success was achieved in significantly more subjects using DFD-01 than Vehicle at day 15 in both Study 1 (P<0.001) and Study 2 (P=0.002), and at day 29 (both studies P<0.001). Treatment success with DFD-01 was significant at day 8 in Study 1 (P=0.003) but not in Study 2 (P=0.156). Erythema, scaling, and plaque elevation scores of target lesions were significantly reduced as early as day 4 with DFD-01. Adverse events were similar between groups, with no increase between 2 and 4 weeks.
CONCLUSION: These studies demonstrate DFD-01’s excellent efficacy and safety for the treatment of extensive psoriasis (10–20% BSA). DFD-01 achieved treatment success in significantly more subjects than Vehicle after 2 and 4 weeks of treatment, and showed early onset of action with improved signs of erythema, scaling and elevation of target lesions after 4 days of treatment. This medium potency formulation provides a safe and effective choice for topical steroid treatment of psoriasis.

J Drugs Dermatol. 2016;15(3):334-342.

BACKGROUND: Cardiovascular morbidity and mortality have been demonstrated to be greater in psoriasis patients than in the general population. Our study aimed to assess the 10-year cardiovascular risk in patients with moderate to severe psoriasis compared with those suffering from other dermatological diseases, using the calibrated Framingham risk score and the Systematic Coronary Risk Evaluation (SCORE) risk charts.
METHODS: A cross-sectional, multicentre study was made of 477 patients, of whom 238 had moderate to severe psoriasis (cases) and 239 were diagnosed with another dermatological disease (controls).
RESULTS: The proportion of patients with intermediate to high 10-year cardiovascular risk using the Framingham equation was significantly higher among psoriasis patients (38.5%; 80/208) than among the controls with other dermatological diseases (23.4%; 50/214, P<.05). No significant differences were observed between the 2 groups with respect to cardiovascular risk using the SCORE risk charts (P=.591). The case group included a greater proportion of obese and morbidly obese patients, as well as patients with higher triglyceride and low density lipoprotein cholesterol levels (P<.05); while high density lipoprotein cholesterol levels were significantly more favorable in patients in the control group (P<.05).
CONCLUSIONS: Cardiovascular risk was greater in patients with moderate to severe psoriasis than in patients with other dermatological conditions, suggesting that early detection and tailored management of risk factors is essential to reducing cardiovascular morbidity in these patients.

J Drugs Dermatol. 2014;13(10):1240-1247.

Acrodermatitis continua of Hallopeau (ACH) is a rare form of pustular psoriasis which poses a challenge to treat and causes considerable pain and suffering for those afflicted. Tumor necrosis factor-alpha (TNF-?) is a pro-inflammatory cytokine involved in the pathogenesis of ACH and other forms of psoriasis. Inhibition of TNF-? has been shown to provide benefit in such inflammatory conditions as rheumatoid arthritis, psoriatic arthritis, and, most recently, plaque psoriasis. In this report, we present the case of a 65-year-old man with a 9-year history of recalcitrant ACH who demonstrated significant and sustained clinical improvement when etanercept, a competitive inhibitor of TNF-?, was added to his treatment regimen of acitretin and topical corticosteroids over a 12-week period.

BACKGROUND: Monoclonal antibodies that target both Interleukin (IL)-12 and IL-23 have shown great efficacy in the treatment of psoriasis. Recent evidence suggests that IL-23 serves a more critical role than IL-12 in the pathogenesis of psoriasis, leading to the development of monoclonal antibodies that specifically target IL-23.
METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab, in order to assess the efficacy and safety profile of each agent.
RESULTS: By week 16, the proportion of patients achieving Physician Global Assessment (PGA) score of clear (0) or minimal (1) and Psoriasis Area and Severity Index (PASI 75) was above 70% among the most efficacious dosage of each agent (P< 0.001 compared to placebo for all agents). The safety profiles of the agents were similar, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, cough, and headache.
CONCLUSION: The anti-IL-23 agents demonstrated a rapid clinical improvement and favorable short-term safety profile. The results of the phase II trials support IL-23 as an essential target in psoriasis treatment.

J Drugs Dermatol. 2015;14(10):1093-1096.

Infliximab is a chimeric monoclonal antibody, which acts by binding to both the soluble and membrane-bound tumor necrosis factor-a. In clinical practice, it is used as either monotherapy or in combination with other systemic therapies, particularly methotrexate. This study reviews clinical response and adverse events in 120 psoriasis patients with moderate-to-severe psoriasis who have received infliximab for a minimum of one year. The medical records of 120 infliximab-treated psoriasis patients at our referral psoriasis clinic in Dallas between 2002-2008 were reviewed for response rates, side effects and concomitant therapies. Of 120 charts reviewed, 112 (93%) patients had plaque type psoriasis, six (5%) had recalcitrant palmoplantar disease and two (1.6%) had severe acropustulosis of Hallopeau. Eighty-four (70%) patients had symptomatic psoriatic arthritis. The mean follow-up time was 2.2±1.1 years. One hundred and nine (91%) of the 120 patients had clearance of their psoriasis (response of more than 90% of initial BSA) at a median time of 12 weeks. Concomitant systemic treatments, primarily methotrexate, were given to 62 (52%) patients. Nineteen patients (16%) discontinued infliximab in the post-one-year treatment period for a variety of reasons, primarily failure to maintain adequate response. One hundred and four (87%) of patients required more than the standard dose of 5 mg/kg every eight weeks to maintain clearance. Infliximab either as monotherapy or in combination with traditional antipsoriatic agents is an effective and well-tolerated treatment option for patients with moderate to severe psoriasis and psoriatic arthritis on therapy for over one year and continuing for the long term.

J Drugs Dermatol. 2011;10(5):539-544.

Etanercept is a self-administered medication that has FDA approval for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Etanercept is a human fusion protein of the tumor necrosis factor receptor (TNFR) and the Fc region of IgG1 that binds to and presumably inhibits the pro-inflammatory and pro-proliferative activity of the tumor necrosis factor (TNF). A recent multisite, randomized, double-blind, placebo-controlled study conclusively demonstrates that etanercept as monotherapy effectively treats patients with moderate-to-severe plaque psoriasis. This effect is dose-responsive, with the etanercept 50 mg twice-weekly dose significantly more effective than the 25 mg twice-weekly dose in reducing the Psoriasis Area and Severity Index (PASI) score over both 12 and 24 weeks of continuous therapy1. Nevertheless, clinical trials do not instruct the dermatologist on how to practically integrate etanercept into a patient’s pre-existing treatment regimen. Many psoriasis patients are already on other systemic therapies or have a medical history that necessitates a tailored approach to their therapy. Further, in some patients, etanercept at 25 mg twice weekly is ineffective in maximally clearing a patient of psoriasis. Below are cases that demonstrate how etanercept can be combined with other medications in order to both maximize clinical efficacy and minimize potential risk.

Psoriasis is an immunologic disorder mediated by T cells and proinflammatory cytokines. Novel biologic therapies, targeted at key pathogenic steps, have been developed and provide efficacy without the potential end-organ toxicity induced by traditional therapies. The biologic therapies currently approved for treatment of psoriasis are classified into 2 categories, as defined by their mechanism of action: inhibition of tumor necrosis factor (TNF) (etanercept, infliximab, adalimumab) and modulation of pathogenic activated T cells (alefacept, efalizumab). This review has been prepared in 2 parts: Part 1 focuses on anti-TNF agents and includes new data that have become available through increased clinical experience and use in eligible patients. Part 2 will present new data on T-cell modulators, new molecules in development, and considerations for optimal therapeutic selection for treatment of patients with psoriasis (Journal of Drugs in Dermatology, March 2009).

The use of cyclosporine to treat psoriasis has been widely adopted since 1997, when the microemulsion form (Neoral) became available. While the causal relationship between cyclosporine and the development of malignant neoplasms has been well described in the transplant literature, it is difficult to apply this relationship to cyclosporine-treated psoriasis, since lower dosages are used (3- 5 mg/kg/d vs. 7-15mg/kg/d) for a shorter duration. Current literature suggests that cancer risk is not increased when cyclosporine is used in dermatologic doses for less than 2 years in healthy patients who are not on other immunosuppressants1. We report two patients with explosive basal cell carcinoma and keratoacanthoma development, respectively, within 3 months of initiation of cyclosporine. Neither patient had a history of skin cancer, had received PUVA therapy, or was on additional immunosuppressive therapy. To our knowledge, there have been no previous reports of the development of similar lesions in cyclosporine-treated psoriatic patients within such a short timeframe. The results of these patients may herald the need for increased awareness by dermatologists for explosively- growing neoplasms in the setting of cyclosporine-treated psoriasis

Background: Combining systemic agents with phototherapy is becoming a standard of care for patients with moderate to severe psoriasis. The combination of adalimumab and phototherapy has not been previously explored.
Methods: In this 24-week single-arm open-label study, adults with moderate to severe psoriasis received adalimumab 40 mg every other week and narrowband (NB)-UVB phototherapy three times a week for 12 weeks and then were followed for 12 weeks without treatment. Response to therapy was determined using the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) affected and Physician’s Global Assessment (PGA) of psoriasis.
Results: Twenty patients were enrolled with mean baseline scores of 17.0 for PASI, 21.2 for BSA and 3.5 for PGA. Half (10/20) of the patients achieved PASI 75 response by week 4. At the end of treatment at week 12, 19 (95%) patients achieved PASI-75, 15 (75%) patients achieved PASI-90 and 11 (55%) patients achieved PASI-100. Seventeen (85%) patients were clear or almost clear (PGA score ≤1). Mean baseline PASI, BSA and PGA scores improved by 95 percent, 93 percent and 80 percent, respectively. Disease improvement was observed through the end of follow up period at week 24. No serious adverse events were noted.
Conclusion: Concurrent use of adalimumab and NB-UVB phototherapy was clinically effective and well tolerated in patients with moderate to severe psoriasis. This combination regimen represents a new treatment option for clinical practice and warrants further investigation in controlled clinical trials.

J Drugs Dermatol. 2011;10(4):366--371.

Background: Guidelines to screen for cardiovascular (CV) risk factors in psoriasis patients have been established. However, the frequency with which dermatologists and nondermatologists screen psoriasis patients for CV risk factors is not well characterized.
Purpose: To determine how frequently psoriasis patients are screened for CV risk factors in the ambulatory care setting and to identify factors affecting screening rates.
Methods: Data from the 2005 to 2009 National Ambulatory Medical Care Survey (NAMCS) were analyzed to determine screening rates for blood pressure, glucose, cholesterol, and body mass index (BMI). The probability of a patient having at least 1 of the 4 risk factors screened was determined and was termed the "composite" score. Screening rates were assessed by physician specialty, patient demographics, and clinical practice characteristics.
Results: There were an estimated 11.4 million psoriasis patient visits from 2005 to 2009. Blood pressure, glucose, cholesterol, and BMI were evaluated at 32.2%, 5.9%, 9%, and 26% of psoriasis visits, respectively, with a composite score of 41.2%. Patients without psoriasis were screened for these CV risk factors at 59.0%, 6%, 8%, and 38.1% of outpatient visits, respectively, with a composite score of 66.3%. The results of a multivariate analysis accounting for patient age differences indicated psoriasis had a statistically significant effect on rates of blood pressure and BMI screening. In general, screening rates were higher if the patient was male, African American, or non-Hispanic, and screening rates were relatively equal across age groups. Higher screening rates were also associated with primary care specialties, faculty practice or community health clinics with contracted physicians, clinics that utilized electronic medical records, practices with a higher percentage of revenue from a Medicare/Medicaid payer, or offices with discounted fees and capitation payment structures.
Limitations: Data from NAMCS are cross-sectional, permitting assessment of screening rates based on visits but not on patients.
Conclusions: Screening for high blood pressure, diabetes, hypercholesterolemia, and obesity are not performed at most outpatient visits for psoriasis. Care should be taken to ensure that patients do receive appropriate screening for the comorbidities associated with psoriasis.

J Drugs Dermatol. 2013;12(1):e14-e19.

We report the results of a nonrandomized, open-label pilot trial investigating the safety, tolerability, and efficacy of bexarotene gel 1% in treating chronic mild to moderate plaque psoriasis. Twenty-four adults with mild to moderate stable plaque psoriasis involving 15% or less of their body surface were enrolled. Patients applied bexarotene gel 1%, using an application frequency escalation regimen, starting at once every other day and increasing to 4 times daily as tolerated and beneficial for up to 24 weeks. The primary efficacy instrument was a Physician’s Global Assessment (PGA) score evaluating the overall response to treatment. This utilized individual signs of psoriasis and the percent of body surface area involvement. Safety assessments included physical examinations, recording of adverse events, and laboratory safety evaluations. Fifteen out of 24 enrolled patients (63%) achieved at least 50% improvement by PGA score at 2 or more consecutive visits, and 6 (24%) achieved clearing of 90% or more. Six patients maintained a response throughout 8 weeks of followup. An increased response appeared to correlate with a higher frequency of gel application. Adverse events occurred primarily at application sites and were mild or moderate in severity. Bexarotene gel 1% was active in treating mild to moderate plaque psoriasis with achievement of durable responses in some patients and was well-tolerated. A randomized, placebo-controlled study would be useful in confirming these results.

Ubiquitous electronic devices, such as smartphones and tablets, have the potential to enable a fundamental shift in the paradigm of healthcare as these devices may allow patients and health care providers (HCPs) to rapidly and remotely communicate with each other. Once fully realized, these devices may facilitate interactions between patients and HCPs. While these devices hold much promise, much work remains in assessing their viability in various diseases. A pilot study was conducted to investigate the use of a tablet-based numeric rating scale to assess improvements in a plaque psoriasis target lesion treated with clobetasol propionate 0.05% spray (CPS). Twenty-eight subjects with plaque psoriasis enrolled and were treated with CPS twice daily for 15 days. Target lesion severity (scale of 0 [no psoriasis] to 10 [very severe psoriasis]) and effectiveness scores (scale of 0 [none] to 3 [severe]) were recorded using a tablet-based system by the investigator and subjects. The tablet was also used to take photos of the target lesion to capture photographic evidence of improvement. Investigator and subject assessed target lesion severity and effectiveness scores improved during the study from baseline to day 15; in addition subjects indicated a high level of satisfaction with CPS treatment. Very few technological failures were reported and captured photographs were consistent visit to visit and of high quality. Taken together, this study supports the use of a tablet-based system to measure and track plaque psoriasis disease progression and also confirmed that CPS is an effective and safe treatment for plaque psoriasis.

J Drugs Dermatol. 2015;14(3):236-241.

Objective: This study examined the relationship between depressive symptoms and related medication adherence and health care costs in older adults (age ? 65 years) with psoriasis.

Design: Prospective longitudinal cohort study over a 2-year post enrollment period in a population of older adults with psoriasis enrolled in managed care.

Setting: A Medicare Health Maintenance Organization (HMO) in southeastern United States with prescription benefits.

Participants: Sixty-three older adults with psoriasis using topical corticosteroids therapy and enrolled in a Medicare HMO for a 2- year continuous period.

Measurement: Upon enrollment, each enrollee was mailed a comprehensive health status assessment battery, which included the Center for Epidemiologic Studies Depression (CES-D) scale. Information on medication adherence (using medication possession ratio) and total health care utilization/costs following enrollment were retrieved from the Medicare HMO database.

Results: Nearly one-fifth of the patient population had depressive symptoms. Patients with psoriasis who had depressive symptoms at the time of enrollment were less likely to be adherent to topical corticosteroid medication (r= -0.29, p<0.01) and less likely to utilize health care resources as evidenced by lower health care costs (r= -0.27, p<0.05), after confounder adjustment.

Conclusions: The prevalence of depressive symptoms in older adults with psoriasis is commonplace, with strong, yet unexplained correlations between presence of depressive symptoms and lower rates of medication and health care service use among these patients.

BACKGROUND: Studies investigating the molecular basis of psoriasis have established the central roles of TNFa, interleukin (IL)-12, IL-22 and IL-23, and now there is increasing evidence that IL-17 plays a vital role in the complex pathophysiology of this disease. Preclinical and phase II studies of medications targeting IL-17 and its receptor have thus far proved to be promising.
METHODS: We reviewed the results of the phase III clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent.
RESULTS: By week 12, the proportion of patients reaching a 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) was comparable between the different agents (secukinumab 83%, ixekizumab 89%, and brodalumab 85%). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction.
CONCLUSION: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis treatment.

J Drugs Dermatol. 2016;15(3):311-316.

BACKGROUND: The advent of biologics has improved patient outcomes in the treatment of moderate-to-severe psoriasis. The time it takes for patients to see clinically meaningful improvement is an important aspect of disease management. OBJECTiIVE: To review the clinical data on the use of biologics in moderate-to-severe psoriasis, identifying which biologics may offer the quickest results. METHODS: A review of the published and presented efficacy data on adalimumab, infliximab, ustekinumab, etanercept, brodalumab, ixekizumab, and secukinumab to estimate the time to achieve clinically meaningful outcome; defined as time for 25% of patients to achieve Psoriasis Area and Severity Index (PASI) 75, or a 50% reduction in mean baseline PASI. RESULTS: Clinically meaningful outcomes were achieved within 2-11 weeks with biologics. Calculated times for 25% of patients to achieve PASI 75 were 2.1 [95% CI 2.0-2.3] weeks (brodalumab), 2.4 weeks (ixekizumab), 3.0 weeks (high-dose secukinumab), 3.5 weeks (infliximab), 4.6 weeks (adalimumab and high-dose ustekinumab), 5.1 weeks (low-dose ustekinumab), 6.6 weeks (high-dose entanercept), and 9.5 weeks (low-dose entanercept). Calculated times for 50% reduction in baseline PASI were 1.8 [95% CI 1.7-1.9] weeks (brodalumab), 1.9 weeks (ixekizumab), 3.0 [95% CI 2.8-3.2] weeks (high-dose secukinumab), 3.5 weeks (adalimumab), 3.7 weeks (infliximab), 5.1 weeks (low-dose ustekinumab), 6.5 weeks (high-dose entanercept), and 10.9 weeks (low-dose entanercept). CONCLUSIONS: Brodalumab may have the most rapid onset of action of any biologic therapy used in psoriasis. Similar results were seen with both outcome measures and will have important implications in psoriasis management.

J Drugs Dermatol. 2018;17(3):247-250.

Background: Central serous chorioretinopathy (CSC), also known as central serous retinopathy (CSR), is a visual impairment, often temporary, usually in a single eye, which mostly affects males in the age group of 20 to 50 but may also affect women. CSC occurring after prolonged use of topical steroids in a patient with psoriasis is a novel complication in the English literature.
Observations: We describe a case of a 25-year-old male, with a 15-year history of corticoid ointment use for psoriasis, who presented with loss of vision secondary to CSR.
Conclusions: All topical steroid treatments were discontinued and the patient recovered his vision completely. Although topical corticosteroids are frequently utilized for psoriasis management with a low rate of complication, clinicians should be familiar with this rare yet distressing condition. Furthermore, patients with increased production of endogenous corticosteroids (e.g., those with Cushing's syndrome, hypertension, or obstructive sleep apnea) should be warned of the potential of chorioretinopathy following prolonged use of topical corticosteroids

J Drugs Dermatol. 2011;10(8):930-933.

BACKGROUND: Patients with moderate to severe psoriasis may not respond adequately to single systemic agent and may require combination systemic therapy.
OBJECTIVE: To evaluate the prevalence, indications, and response to combination systemic therapy with ustekinumab for psoriasis in a tertiary referral center.
METHODS: This retrospective study comprised 102 psoriasis patients treated with ustekinumab at a single tertiary care center. Data was collected pertaining to history of psoriasis, past and current therapies including use of concomitant psoriasis agents, response to therapy, and side effects while on ustekinumab.
RESULTS: Twenty-two of 102 (22%) patients were identified as receiving combination systemic treatment involving ustekinumab and at least one additional agent. The most common indication for combination therapy was psoriatic arthritis (35%), followed by bridging therapy (26%), inadequate psoriasis control (13%), prevention of non-melanoma skin cancers (17%), and control of palmoplantar disease (9%). Methotrexate was the additional agent in 12 patients, cyclosporine in 7 patients, acitretin in 5 patients, and 1 patient received a second biologic agent, first etanercept and then adalimumab. Overall, the reduction in body surface area (BSA) was 80% for patients on combination therapy. For those patients on combination therapy for psoriatic arthritis, 75% had resolution or stabilization of their symptoms. Only one patient, receiving cyclosporine, discontinued combination therapy due to adverse side effects.
CONCLUSION: Combination systemic therapy with ustekinumab can be effective and well tolerated for patients who cannot be adequately treated with ustekinumab alone.

J Drugs Dermatol. 2013;12(10):1098-1102.

The International Dermatology Outcome Measures (IDEOM) Group was established to develop validated and standardized patient-centered outcome measures in dermatology that meet the needs of stakeholders and can be used in clinical practice as well as clinical research. At this meeting, we aimed to define the final core domain set to be assessed in psoriasis clinical research and to identify which of the current psoriasis assessment instruments appropriately address those domains. Specifically, we sought to ascertain stakeholder input on domain match and feasibility of multiple psoriasis instruments. We presented 19 physician-reported and 23 patient-reported outcome measures at the meeting. Stakeholders anonymously voted on the validity and feasibility of each instrument. Validity was rated as: green (good), amber (fair), red (poor), and white (not enough information). Feasibility was rated as: green (feasible), amber (concerns about some aspects of feasibility), red (not feasible), and white (not enough information). Eighteen physician-reported and 20 patient-reported instruments received a favorable green or amber rating for validity from the majority of voters. Seventeen physician-reported and 19 patient-reported instruments received a green or amber rating for feasibility from the majority of voters. A significant proportion of the psoriasis instruments received a good or fair vote for measuring their intended psoriasis domains in a feasible manner. We will continue to refine our voting methodology and incorporate patient input into our process of defining psoriasis domains and developing validated instruments.

J Drugs Dermatol. 2017;16(8):770-777.

Erythema gyratum repens (EGR) is a rare skin syndrome often associated with internal malignancies, and thus considered paraneoplastic1. There are cases of erythema gyratum repens in the literature associated with other dermatoses without underlying malignancies1. We present a case of resolving psoriasis which evolved into erythema gyratum repens when treated with acitretin.

BACKGROUND: A novel 0.05% betamethasone dipropionate emollient spray (DFD-01) was formulated to optimize penetration of steroid to the epidermal layers affected by psoriasis.
OBJECTIVE: To compare the efficacy and safety of medium potency DFD-01 with super potent augmented betamethasone dipropionate 0.05% lotion (Diprolene) for the topical treatment of moderate plaque psoriasis.
METHODS: Adults with moderate plaque psoriasis (Investigator Global Assessment [IGA]=3; 10–20% BSA) were randomized 2:1:1 to DFD-01, Diprolene, or Vehicle. Products were applied twice daily to affected areas for 14 days. Treatment success was defined as IGA=0 or 1 and ≥2-grade improvement from baseline. IGA and target lesion Total Sign Score (TSS; sum of erythema, scaling, and plaque elevation scores) were assessed at baseline and at days 4, 8, and 15. Adverse events (AEs) were recorded.
RESULTS: 351 subjects with moderate psoriasis were randomized to DFD-01 (n=174), Diprolene (n=90), or Vehicle (n=87). Mean BSA was 13–14%. Treatment success was achieved in 19.0% DFD-01, 18.9% Diprolene, and 2.3% Vehicle (P<0.001 DFD-01 vs Vehicle) at day 15. Treatment success at day 8 was 10% DFD-01, 6.7% Diprolene, and 1.2% Vehicle (P=0.003 DFD-01 vs Vehicle). TSS was significantly reduced with DFD-01 compared with Vehicle at days 4, 8, and 15 (P≤0.006) and compared with Diprolene at day 4 (P=0.010). DFD-01 relieved signs of erythema and scaling earlier than Diprolene or Vehicle, showing significant improvements on day 4 (P≤0.048). All products were well tolerated. Significantly more burning/stinging was reported with Diprolene than DFD-01 (13.6% vs 4.1%, P=0.006).
CONCLUSION: Medium potency DFD-01 was efficacious for the treatment of moderate psoriasis. DFD-01 demonstrated similar efficacy to super potent Diprolene lotion. Results at 4 and 8 days indicate that DFD-01 shows early improvement in some subjects. DFD-01 was well tolerated and had an excellent safety profile.

J Drugs Dermatol. 2016;15(2):154-162.

Background: This study compared the efficacy of a novel, topical class I synthetic, 0.10% fluocinonide corticosteroid with two other class I corticosteroids and placebo for the treatment of plaque psoriasis.

Methods: A 0.5 gram dose of fluocinonide 0.1% cream, clobetasol propionate 0.05% cream, halobetasol propionate 0.05% cream, and placebo ointment were applied to test sites on one psoriatic plaque per patient (n=5). Test sites were outlined according to the Scholtz-Dumas bioassay. Test sites were assessed by a blinded evaluator (1=psoriasis worsened to 5=psoriasis clear or almost clear), cleaned and medications were reapplied on days 3, 5, 7, 10 and 12.

Results & Conclusion: The three class I corticosteroid products were comparably effective, numerically and statistically, in clearing the psoriatic plaques. Upon completion of treatment, 60–80% of active-treated sites were clear or almost clear of psoriasis compared to zero with the placebo.

A 50-year-old African-American woman presented to the dermatology clinic with a pruritic eruption of 3 years’ duration. On clinical examination, the patient had well-demarcated, pink, atrophic plaques and superficial erosions over the inframammary folds and mid-chest. She also had well-demarcated, hyperpigmented, hyperkeratotic scaly plaques over the abdomen, suprapubic region, elbows, knees, and back with sporadic small superficial blisters. A punch biopsy of the right abdomen was performed and revealed psoriasiform epidermal hyperplasia, focal parakeratosis, and acantholysis throughout the superficial spinous and granular layers. Only a sparse inflammatory infiltrate was present in the underlying dermis. Clinical and histological findings supported the diagnosis of pemphigus foliaceus (PF), but psoriasis was included in the differential diagnosis due to the presence of discrete plaques with an erythematous border. We hypothesize that patients with psoriasiform presentations of PF may be misdiagnosed with plaque psoriasis. It is important to distinguish between PF and psoriasis as there is evidence that ultraviolet light, a common treatment for psoriasis, may exacerbate PF. We document and highlight this atypical psoriasiform presentation of PF in a patient with skin of color to raise awareness and improve diagnosis and outcomes.

J Drugs Dermatol. 2018;17(4):471-473.

OBJECTIVES: To demonstrate the efficacy and safety of calcitriol ointment (3 mcg/g) compared to betamethasone diproprionate ointment in the treatment of nail psoriasis.
DESIGN: Single-center, double-blind study.
SETTING: One academic center.
PARTICIPANTS: 10 adult male and female subjects with psoriasis of the fingernails and/or toenails.
MEASUREMENTS: The primary efficacy evaluation was the absolute reduction of nail thickness (mm) of the target nail. A secondary endpoint was the improvement in the Physician Global Assessment score of disease severity.
RESULTS: Patients treated with either betamethasone diproprionate ointment or calcitriol ointment demonstrated a similar reduction of nail thickness of the selected target nail. The difference between the two groups was not statistically significant (P=0.42).
CONCLUSION: This small study illustrates that calcitriol ointment may be as effective as betamethasone diproprionate in the treatment of nail psoriasis, and its promise should be further investigated in a subsequent larger trial.

J Drugs Dermatol. 2014;13(8):912-915.

BACKGROUND: Interleukin (IL)-17A is a key cytokine in the pathogenesis of psoriatic disease of the skin and joints. In phase 3 trials, secukinumab, a fully human anti–IL-17A monoclonal antibody, demonstrated robust efficacy in psoriasis, with rapid onset, high response rates, and durable response.
OBJECTIVE: To evaluate the efficacy of secukinumab in subjects with psoriasis and concomitant psoriatic arthritis (PsA) with respect to psoriasis symptoms and physical function, we conducted pre-specified subanalyses of the phase 3 FIXTURE and ERASURE trials.
METHODS: The 52-week FIXTURE and ERASURE trials randomized subjects with moderate-to-severe plaque psoriasis to subcutaneous secukinumab 300 or 150 mg (Baseline, weeks 1, 2, 3, every 4 weeks from week 4 until week 48), etanercept 50 mg (twice weekly through week 12, once weekly thereafter through week 51; FIXTURE only), or placebo. In this analysis, changes in Health Assessment Questionnaire–Disability Index (HAQ-DI) and PASI 75 responses were assessed in subpopulations with concomitant PsA (n=196, FIXTURE; n=171, ERASURE).
RESULTS: Physical functioning (mean change from Baseline in HAQ-DI) was greater with secukinumab 300 mg vs. placebo at week 12 in both trials (FIXTURE, -0.41 vs. 0.02/P=0.0001; ERASURE, -0.35 vs. -0.08/P=0.0003); corresponding values were -0.29 for etanercept and -0.19 for secukinumab 150 mg in FIXTURE and -0.18 for secukinumab 150 mg in ERASURE. Greater responses were seen in subjects with greater Baseline disability (HAQ-DI ≥05). Week 12 PASI 75 responses were higher with secukinumab 300 mg/150 mg vs. placebo in FIXTURE (72%/59% vs. 2%) and ERASURE (68%/70% vs. 4%; all P<0.0001) and with secukinumab 300 mg vs. etanercept (72% vs 39%; P=0.0084).
CONCLUSION: Secukinumab 300 mg produced significant improvement in psoriasis and physical functioning in subjects with concomitant PsA.

ClinicalTrials.gov numbers: NCT01358578 (FIXTURE); NCT01365455 (ERASURE)

J Drugs Dermatol. 2015;14(8):821-833.

Data from two Phase 3, double-blind, randomized, vehicle-controlled parallel studies were evaluated to determine the efficacy and safety of twice daily desoximetasone 0.25% spray for the treatment of plaque psoriasis. In addition to global disease assessments, scaling assessments were performed at baseline and at weeks 1, 2, and 4.

To qualify for inclusion, subjects were required to have a clinical diagnosis of stable plaque psoriasis involving ≥10% of the body surface area (BSA), a combined target lesion severity score (TLSS) of ≥7 for the target lesion, a plaque elevation score of ≥3 (moderate) for the target lesion, and a Physician Global Assessment (PGA) score of 3 (moderate) or 4 (severe) at baseline for the overall disease severity.

At the baseline visit, the mean proportions of BSA affected by psoriasis were 17% (range 10% to 86%) in the desoximetasone 0.25% spray group and 16% (range 10% to 70%) in the vehicle spray group. Approximately 90% of the patients in each group had moderate to very severe scaling at baseline. Desoximetasone 0.25% spray was effective with significant improvements in overall severity and was well tolerated, with dryness, irritation, and pruritus at the application site being the only reported adverse events occurring in >1% of patients, each of which occurred in less than 3% of patients.

As a large proportion of psoriasis patients (94%) have reported being bothered by scaling, the relief of scaling was examined in these studies. At week 1, 69.7% of patients on desoximetasone 0.25% spray had scaling that was considered clear / almost clear / mild compared with 48.3% for those on vehicle spray (P= .0027). By week 4, the proportion of patients with clear / almost clear / mild scaling had risen to 83.9% in the desoximetasone 0.25% spray group (P < .0001). After four weeks of treatment, 66.4% of patients in the topical corticosteroid group had an overall improvement of at least two grades of disease severity. This demonstrates that desoximetasone 0.25% spray provided fast and effective relief of scaling in patients with plaque psoriasis affecting 10% to 86% of their BSA.

J Drugs Dermatol. 2015;14(8):835-840.

Acute pustular psoriasis is characterized by fiery-red erythema followed by formation of pustules. Precipitating factors include drugs, infections, pregnancy, solar irradiation, and psychological stress. We present a case of a woman who developed acute onset of pustular psoriasis precipitated by hydroxychloroquine therapy and systemic steroids. The patient’s course was complicated by leukocytoclastic vasculitis presumptively caused by levofloxacin.

Topical corticosteroids are widely used in the treatment of psoriasis. This study was conducted to compare the effi cacy and safety of clobetasol propionate (CP) 0.005% spray to calcipotriene 0.005%-betamethasome diproprionate 0.064% (C-BD) ointment in patients with moderate to severe plaque psoriasis. Assessments were made at baseline, week 2, week 4 (end of treatment) and week 8 (4 weeks posttreatment). An assessment for Overall Disease Severity (ODS) found that 75% of CP spray-treated patients achieved a rating of clear or almost clear after 4 weeks of treatment compared to 45% of C-BD ointment-treated patients (P=.003). Adverse events were reported by less than one-third of patients from each treatment group (31% for CP spray and 33% for C-BD ointment).

2008 JDD Case Report Contest Winner

Treatment of patients with moderate-severe psoriasis and/or psoriatic arthritis includes systemic biologic, antimetabolite, and im- munosuppressive therapy. However, adverse events such as serious infectious complications must be considered before start- ing therapy and throughout treatment. The authors describe the case of a male on combination etanercept and methotrexate for psoriasis and psoriatic arthritis for years who developed a spontaneous epidural abscess with resulting quadriplegia. In addition, a review of the literature was performed looking at the risk of serious infectious complications with antitumor necrosis factor (anti-TNF) monotherapy or combination therapy with methotrexate fro the treatment of psoriasis and rheumatoid arthritis. Serious infectious risk does not appear to be increased with etanercept or other anti-TNF agents either alone or in combination with methotrexate. Nevertheless, clinicians are cautioned to carefully weigh the risks and benefits of treating with anti-TNF agents in patients who are prone to infection.

TNF-alpha is a key cytokine in innate immune responses and is increased in psoriatic lesions. TNF-alpha has many effects, ranging from inflammation to apoptosis. These effects are reviewed to better understand the role of TNF-alpha as it relates to the pathogenesis and treatment of psoriasis. TNF-alpha increases production of pro-inflammatory molecules (e.g. IL-1, IL-6, IL-8, NF-kappaB, vasoactive intestinal peptide) and adhesion molecules (e.g. intercellular adhesion molecule-1, P-selectin, E-selectin). TNF-alpha promotes apoptosis through binding to the TNF-receptor 1; however, psoriatic lesions are hyperproliferative despite an increase in TNFalpha. This paradox is partially explained as NF-kappaB activation seems to inhibit TNF-alpha-induced apoptosis. The importance of TNF-alpha and apoptosis in psoriasis is shown through the review of clinical trials using anti-TNF-alpha immunobiologics (e.g. etanercept, infliximab) and apoptosis-inducing treatments that result in clinical improvement of the disease.

BACKGROUND: The efficacy of biologic treatment for psoriasis has not been compared to that of conventional systemic therapies and phototherapy outside of clinical trial settings.
DESIGN: Retrospective, cross-sectional
METHODS: All patient visits with a code for psoriasis (ICD-9 696.1) in the clinical practice of two dermatologists with a high percentage (over 70% of chief complaints) of psoriasis patients from Jan 1, 2008 to Jan 4, 2012 inclusive were included in this retrospective data analysis. Patients were excluded if the baseline Physician's Global Assessment (PGA) at start of treatment was unknown, or less than 3 (moderate). The practice is a comprehensive psoriasis care center in the Northeastern United States serving a metropolitan population of over 4 million people. Patients were divided by treatment type (biologic, conventional systemic or both) and history of previous treatments. Patients were evaluated by Body Surface Area (BSA), PGA, Simple-Measure for Assessing Psoriasis Activity (S-MAPA, calculated by BSA multiplied by PGA). Patients were evaluated at baseline, 8, 12, 16, and 24 weeks after start of treatment. Patients must have completed at least 8 weeks on a single treatment in order to be included.
RESULTS: 46 courses of biologics, 12 courses of conventional systemic therapies, and 18 courses of both together were identified with PGA 3 or greater at baseline. Baseline S-MAPA for biologics was 74, for non-biologic systemics was 62.25. At week 24, S-MAPA improved 70.2% over baseline in patients treated with biologics, patients treated with non-biologic systemics improved by only 40.4% (P<0.05). The average number of prior treatments for patients on biologics was 1.87 versus 1.25 for patients on conventional systemic therapies (P=0.169).
CONCLUSION: Biologics show superior results to conventional systemic therapies (70% improvement versus 40% improvement) for the treatment of patients with moderate to severe psoriasis, as measured by decrease in S-MAPA (PGA multiplied by BSA) at week 24. These results were observed despite the fact that patients on biologics had a greater baseline severity and had a greater number of previous treatments.

J Drugs Dermatol. 2013;12(8):861-866.

Background: Clobetasol propionate 0.05% spray is available for treating moderate-to-severe plaque psoriasis; however, there is limited information with plaque psoriasis of the scalp.
Objective: Evaluate the efficacy, safety, and quality-of-life impact of clobetasol propionate 0.05% spray in patients with moderate to severe plaque psoriasis of the scalp.
Methods: Multicenter, randomized, double-blind, vehicle-controlled study involving 81 men and women with moderate-to-severe (Global Severity Score [GSS] = 3 or 4) plaque psoriasis of the scalp. Eligible patients were treated with clobetasol propionate 0.05% spray or vehicle spray, which was applied twice daily for up to four weeks. The primary efficacy end point was the GSS of psoriasis of the scalp after four weeks. Safety assessments included local tolerability, presence of Cushing's syndrome, and adverse events.
Results: At the end of treatment, 85 percent (35/41) of patients in the clobetasol propionate 0.05% spray group achieved success (GSS clear or almost clear), compared with 13 percent (5/40) in the vehicle spray group (P < .001). The proportion of patients treated with clobetasol propionate 0.05% spray who achieved a rating of clear (GSS = 0) after two weeks and at the end of treatment was 12 percent and 51 percent, respectively. Clobetasol propionate 0.05% spray was well tolerated, and there were no serious adverse events or reported cases of folliculitis or Cushing's syndrome.
Conclusion: Treatment with clobetasol propionate 0.05% spray for up to four weeks is effective and well tolerated for moderate-to-severe plaque psoriasis of the scalp.

J Drugs Dermatol. 2011;10(8):888-895.

Background: The safety of biologic agents for psoriasis treatment is of particular importance in patient groups at higher risk for adverse events. We assessed the safety and efficacy of alefacept in elderly, obese, and diabetic patients with moderate to severe chronic plaque psoriasis by integrating data from phase 2 and 3 clinical studies and their extensions. Observations: Ninety-nine elderly, 652 obese, and 122 diabetic patients received at least 1 course of alefacept. In each cohort, accidental injury, headache, and pharyngitis were among the most common adverse events; infections were primarily common colds; and malignancies were mostly skin carcinomas. No opportunistic infections were reported. Safety was maintained over repeated courses. The safety profile of alefacept in each cohort was consistent with that of the overall population; however, additional data are needed to confirm our findings in the elderly and diabetic subgroups in the later courses due to the limited sample sizes. In course 1, 24% to 33% of patients achieved 75% or greater improvement in Psoriasis Area and Severity Index (PASI) at any time, with further enhancement of benefit with subsequent courses (eg, course 3, 41% to 58%). Conclusions: Alefacept was well-tolerated and effective in elderly, obese, and diabetic patients with psoriasis.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease associated with psoriasis. Arthritis mutilans is a rare clinical form of PsA in which osteolysis and destructive changes in the joints lead to irreversible deformity and loss of function. This paper describes three patients with psoriatic arthritis mutilans who were followed for up to two years and received treatment with etanercept, a TNF-alpha targeting agent that is used to treat PsA and psoriasis. Although these patients experienced significant joint and skin improvement with etanercept therapy, they retained lasting deformities from years of progressive disease. In order to prevent permanent joint damage, early recognition and treatment of PsA are critical. This highlights an important role for dermatologists in identifying early joint symptoms that may be suggestive of PsA in patients with psoriasis.

BACKGROUND: Efalizumab was voluntarily withdrawn from the market in April 2009 after four cases of Progressive Multifocal Leukoencephalopathy.
OBJECTIVE: To review the baseline characteristics and psoriasis phenotypes of patients with prior excelled response to efalizumab, and to determine the response of these patients to prior as well as subsequent therapies. By defining this subgroup of patients, particularly relating to palmoplantar psoriasis, future therapeutic considerations could be improved.
DESIGN: A retrospective review of 72 patients who were on efalizumab at the time of market withdrawal was conducted. Data was obtained through chart review of patients at a specialty psoriasis clinic in Dallas, TX.
MAIN OUTCOMES AND MEASURES: Patient characteristics, details of efalizumab use, and efficacy of efalizumab compared with other psoriasis treatment modalities.
RESULTS: Of the 72 patients, 24 (33%) were found to have palmoplantar disease. As a group, these patients were older, more likely to be female, and less likely to have a family history of psoriasis. 48 patients (67%) were on one or more systemic and/or biologic medication prior to starting efalizumab. Their BSA improved from 5.45 to 0.8 as a group. Six patients were identified as having failed TNF alpha antagonist treatment prior to starting efalizumab. All responded well to the medication with an average BSA of 0.54. Five of these six patients had evidence of palmoplantar disease prior to starting efalizumab and five of these six patients were female. Eleven patients (15%) experienced neurologic side effects and 13 (18%) had infections while on efalizumab treatment.
LIMITATIONS: This was a retrospective review. Quality of life issues could not always be fully assessed from the data available.
CONCLUSIONS AND RELEVANCE: Efalizumab was effectively utilized in our clinical practice to treat patients with palmoplantar psoriasis, including six patients who had failed prior treatment with one or more TNF alpha antagonist agents.

J Drugs Dermatol. 2014;13(6):712-718.

The International Dermatology Outcome Measures (IDEOM) group, comprising patients, physicians, health economists, industry partners, payers, and regulatory agencies, was established to develop unified and validated patient-centered outcome measures in dermatology in response to increasing demand to quantify effectiveness of treatments and performance outcomes among providers. IDEOM has chosen to start with psoriasis outcome measures, and then apply its methodology to other dermatologic diseases. In this paper, we review the background and progress to date of IDEOM, including an update of IDEOM activities as of our 2016 meeting in Washington DC, USA. Briefly, the progress-to-date of a Delphi process to create outcome measures for psoriasis was reviewed, including preliminary data from the first round of Delphi voting. Updates were also heard from industry partners including the National Psoriasis Foundation (NPF) and the US Food and Drug Administration (FDA). Furthermore, plans to establish outcome measures for hidradenitis suppurativa (HS) were discussed.

J Drugs Dermatol. 2017;16(2):119-124.

Agents that safely provide long-term control of psoriasis are needed. To determine the safety and efficacy of extended efalizumab therapy, 339 patients with moderate to severe chronic plaque psoriasis received 2 mg/kg subcutaneous (SC) efalizumab weekly for 12 weeks. At Week 12, 290 patients who achieved ?50% Psoriasis Area and Severity Index (PASI-50) improvement or a static Physician’s Global Assessment grading of “mild,” “minimal,” or “clear” entered maintenance treatment with weekly SC efalizumab. At Week 12, 82%, 41%, and 13% of 339 patients achieved a PASI-50, PASI-75, and PASI-90 response, respectively. At 15 months, 65%, 50%, and 25% of patients achieved a PASI-50, PASI-75, and PASI-90 response, respectively (intent-to-treat, n = 339). The incidence of adverse events did not increase over time, and no new common adverse events were reported. The majority of patients experienced sustained efficacy with no increase in toxicity. This study is planned to continue; patients will receive up to 36 months of continuous efalizumab.

Tumor necrosis factor-α (TNF-α) inhibitors, such as adalimumab, are often used to treat psoriasis and psoriatic arthritis. While it is well known that these agents increase the risk of reactivation tuberculosis, recent evidence suggests that the risk of other nontuberculous mycobacterial (NTM) infections is on the rise. We report cutaneous Mycobacterium fortuitum in a 60-year-old woman with psoriasis who had been receiving adalimumab therapy for psoriatic arthritis for six months. No other risk factors were identified. M. fortuitum was cultured from a lesion on the right leg. Following resolution of the lesion, the patient has been successfully treated with infliximab infusions and subsequently certalizumab without complication for the past three years. To our knowledge, this is the first report of M. fortuitum occurring in a patient receiving adalimumab with successful subsequent treatment without complication while on another TNF-α inhibitor.

J Drugs Dermatol. 2011;10(8):927-929.

Background: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated. Objective: To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe plaque psoriasis. Methods: A total of 912 patients received 50 mg subcutaneous etanercept once weekly (QW) for the first 12 weeks of this extension study. Thereafter, eligible patients could maintain the 50 mg QW dose (n=321) or escalate to 50 mg twice weekly (BIW; n=591) anytime thereafter based on one of three predetermined criteria. Results: Etanercept was well tolerated during 1056 patient-years of exposure; no difference was observed between the 50 mg QW and 50 mg BIW dosages in rates of adverse events and infections. Improvement in skin disease was maintained throughout the study. Patients who stopped and then restarted etanercept also showed improvement in psoriasis. Conclusion: Psoriatic patients continued to benefit from open-label etanercept treatment, both continuous and interrupted therapy, which was generally well tolerated after a combined 2.5 years of experience.

OBJECTIVE: To examine real-world use and patient outcomes with apremilast, an oral PDE4 inhibitor, in the dermatology practice set-ting for treatment of patients with moderate to severe plaque psoriasis.

METHODS: This retrospective, multicenter, longitudinal, observational cohort study used Modernizing Medicine’s electronic medi-cal record (EMR) database of >5000 US dermatology providers. There were 7517 adults aged ≥18 years with a psoriasis diagnosis (ICD-9, ICD-10) who received apremilast therapy from October 1, 2015, to January 31, 2016, and were included in effcacy and safety analyses. Among patients who switched from non-apremilast to apremilast monotherapy, the majority (74.2%) switched from prior topical treatment.

RESULTS: At apremilast initiation, in systemic-naive and systemic-experienced patients, mean (SD) Physician Global Assessment (PGA) was 2.79 (0.13) and 2.48 (0.15); mean (SD) psoriasis-affected body surface area (BSA) was 17.85% (2.27) and 12.93% (2.59); and mean itch numeric rating scale (NRS; 0=no itch, 10=worst itch possible) score was 4.14 and 3.82, respectively. Within 6 months of apremilast initiation, PGA decreased (mean [SD]) in systemic-naive patients (−1.71 [0.19], P less than0.001) and systemic-experienced pa-tients (−1.02 [0.18], P less than 0.001); 26.8% (systemic-naive) and 25.5% (systemic-experienced) of patients achieved a PGA score of 0 or 1. Likewise, statistically signifcant reductions in BSA were noted in systemic-naive patients (~62% reduction from baseline; P less than 0.01) and systemic-experienced patients (~60% reduction from baseline; P=0.002). Mean itch NRS decreased to 2.38 in systemic-naive patients (P=0.139) and 0.0 in systemic-experienced patients (P=0.034). Of 160 patients with ≥1 assessment of patient-perceived overall treatment effectiveness, 138 (86.2%) strongly/somewhat agreed apremilast was effective in clearing their skin of psoriasis. For safety analyses, body weight was available in the EMR database and decreased in systemic-naive patients (−1.75 kg) and systemic-experienced patients (−1.09 kg).

Conclusions: Findings support the effectiveness of apremilast in patients with moderate to severe psoriasis in dermatology clinical practices. Patients perceived apremilast to be effective.

J Drugs Dermatol. 2017;16(12):1240-1245.

Background: Psoriasis is a common disorder affecting 1–3 percent of the general global population. Many therapeutic modalities have been suggested for treatment of this condition, but still there is no definite treatment for this disease. The objective in this study was to evaluate the efficacy of topical azelaic acid gel versus placebo in the treatment of psoriasis vulgaris. Patients, Materials and Methods: This study was a single-blinded randomized clinical trial. Overall, 31 patients were selected and the left or right sided lesions of the patients were randomized to receive either 15% azelaic acid or gel twice daily for a one-month period. Two symmetrical lesions with almost similar severity in every patient were selected and considered as index lesions to evaluate lesion response to treatment. The severity of erythema, scaling, hyperkeratosis and pruritus of the index lesions were scored in range of 0–3 for each lesion by the investigator at the baseline and follow up visits. The percent of involvement of each side of body was also measured using rule of nines. The collected data were analyzed using statistical tests including Mann-Whitney and ANOVA tests. Results: There was no significant difference between the two groups before treatment (P>0.05). After treatment, however, except pruritus, there was significant difference between the two groups (P<0.05). There was no significant difference regarding total psoriasis score between the two groups before treatment (P>0.05). After treatment, however, there was significant difference between the two groups (P<0.05) in favor of more efficacy for azelaic acid. There was no significant difference regarding percent of body involvement between the two groups before treatment (P>0.05). After treatment, however, there was a significant difference between the two groups (P<0.05) in favor of more efficacy on the part of azelaic acid gel. Discussion: The results of our study showed that 15% azelaic acid gel was effective in reduction of purities, scaling and hyperkeratosis of psoriasis plaques. This treatment was also effective in reduction of skin involvement with psoriasis. It is recommended that a longer study be performed that can better evaluate the efficacy of this treatment against plaque-type psoriasis.

The objective of this study was to document the disease burden associated with moderate to severe plaque psoriasis, and assess the impact of efalizumab psoriasis treatment in improving patient-reported outcomes. This included analysis of patient-reported dermatology- related quality of life (DRQL) and psoriasis symptom scores among patients with moderate to severe psoriasis participating in three phase III, randomized, double-blinded, parallel-group, placebo-controlled, multi-center clinical trials conducted to evaluate the efficacy and safety of efalizumab. A total of 1,242 patients with moderate to severe psoriasis treated either with efalizumab

1.0 mg/kg /wk or placebo were followed for 12 weeks. DRQL and psoriasis symptom severity were assessed at baseline (pre-treatment) and at the end of the first treatment phase (12 weeks). DRQL was measured using the Dermatology Life Quality Index (DLQI). Symptoms were measured using the Psoriasis Symptom Assessment (PSA) and an Itch scale. Disease burden was assessed at baseline by examining responses to individual questions of the DLQI, PSA, and Itch patient-reported outcome measures. The impact of treatment on disease burden was assessed over a 12-week double-blind study period by comparing changes in DLQI, PSA, and Itch scale scores between the active treatment and placebo groups. Patient-reported outcomes were also assessed during a 12-week extended treatment phase.

Prior to treatment, the responses to DLQI and PSA items revealed significant disease burden. Greater than 90% of patients reported being embarrassed or self conscious because of their skin, 53% reported that their skin prevented them from working or studying, and 98% reported that scaling and itching was bothersome. Compared to placebo-treated patients, efalizumab-treated patients showed significant improvement in patient-reported outcomes, reducing the limitations and burden associated with moderate to severe psoriasis within each of the three studies, as measured by DLQI (p<0.001), PSA-Severity (p<0.001), PSA-Frequency (p<0.001), and Itch (p<0.001) scores. Across all measures, the proportion of patients that improved on both statistical and clinical criteria for meaningful improvement was at least twofold greater among efalizumab- treated patients than in placebo-treated patients. The benefit of efalizumab was maintained over the course of an additional 12 weeks during an extended treatment phase.

In conclusion, patients with moderate to severe plaque psoriasis reported significant DRQL burden and symptom severity at baseline, but efalizumab significantly improved patient-reported DRQL and reduced the frequency and severity of psoriasis symptoms during 12-week double-blind and 12-week extended treatment periods.

Skin microbiome studies have elucidated clinically pertinent information regarding its potential role in the pathogenesis of certain inflammatory skin disorders. Two of the most commonly diagnosed chronic inflammatory skin disorders that have been connected to perturbation of the skin microbiome are psoriasis (PS) and atopic dermatitis (AD). The objective of this brief review is to recapitulate some of the novel findings concerning the microbiome’s role in AD and PS.

J Drugs Dermatol. 2015;14(2):127-130.

Down syndrome (DS) is the most common chromosomal disorder and a major cause of mental retardation. Down syndrome phenotype is complex and may present a combination of dysmorphic features, congenital heart disease and immunological deficiency. Psoriasis it has been noted to be 0.5%-8% in patients with DS and numerous factors can limit the use of therapeutic options, in particular long-term organ-specific toxicity, and the risk of opportunistic infections. It is still debated whether the use of biologics in the treatment of DS-related psoriasis is safe. We have valuated the efficacy and safety of ustekinumab treatment in-patient with DS suffering from plaque type psoriasis. A 31-year-old patient suffering from plaque type psoriasis since the age of 14, showed a PASI score of 12 after the failure of anti-TNF agents. We switched the patient to ustekinumab treatment at the standard dose of 45 mg subcutaneously initially and 4 weeks later, followed by 45 mg every 12 weeks. The patient showed a significant improvement of the PASI score already after 4 weeks of treatment and further improvements were observed throughout the treatment. We report the first case of DS-correlated psoriasis patient treated for a long-term period with various biologics, showing a satisfactory safety profile undergoing treatment. In our experience, ustekinumab has demonstrated a high efficacy, relatively rapid onset of action, favorable safety profile, and can be considered a good treatment option even after failure to respond to other biologic therapies in patient with DS.

J Drugs Dermatol. 2012;11(8):1000-1002.

BACKGROUND: Acitretin is indicated for severe psoriasis, but it is also a potent teratogen whose use should be avoided in women of childbearing potential. Topical medications, phototherapy, cyclosporine A, and new biologic agents provide safer alternatives for women of childbearing age with moderate to severe psoriasis.
PURPOSE: To determine the demographics of acitretin prescribing patterns as an assessment of acitretin use in women of child-bearing potential.
METHODS: We examined National Ambulatory Medical Care Survey (NAMCS) data from the years 1990-2009 to determine demographic data on patients who were prescribed etretinate or acitretin. We used age under 50 as a proxy for childbearing potential.
RESULTS: From 1996-2009, there were an estimated 29 million office visits for psoriasis. Females accounted for 14.3 million of these visits, and 6.5 million (45.6%) of them were under the age of 50. The NAMCS contained only one record of a female patient under the age of 50 being prescribed acitretin from 1996-2009, the years during which acitretin had been available in the United States. This corresponds to an estimated 2.3% of all psoriasis patients prescribed acitretin during this time (20,000 out of 890,000).
LIMITATIONS: The NAMCS estimates national trends based on a large nationwide database. While the use of acitretin in women under 50 is low, the precision of the estimate is limited by the small sample size provided by this database.
CONCLUSIONS: There are now many alternative treatments besides acitretin for women of childbearing potential with moderate to severe psoriasis. Acitretin is used at most infrequently in this population. In females of reproductive potential, acitretin should be reserved for non-pregnant patients who are unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments.

J Drugs Dermatol. 2013;12(7):799-802.

Oleic acid is a monounsaturated fatty acid with a known action of penetration enhancer which has been used for various purposes, such as a tanning increaser. Narrow-band ultraviolet B (UVB) is a also first-line treatment for psoriasis. The purpose of this study was to evaluate if the use of a 5% oleic acid emulsion previous to the phototherapy sessions was useful in reducing the total dosage necessary for whitening in patients with psoriasis. Forty-four patients were included, 24 received application of the emulsion before phototherapy and 20 received phototherapy with no emulsion. Patients received the UVB sessions just to achieve a reduction of 80% of the basal PASI. The total dose received and number of sessions were compared within the 2 groups. A reduction in these parameters (29.68 J/cm2 vs. 18.16 J/cm2; 24 vs. 19 sessions) was seen in the group that received application of the emulsion. However, this was not statistically significant. The fact that we did not achieve the statistical significance may be due to the small sample size. These results must be cautiously interpreted and confirmed with further studies.

BACKGROUND: Calcipotriene ointment and cream are effective treatments for psoriasis, but many patients with scalp psoriasis prefer lighter, less messy vehicles.
OBJECTIVES: To evaluate the efficacy and safety of calcipotriene foam, 0.005%, for plaque-type psoriasis of the scalp.
METHODS: Subjects (n=363) were randomized into an 8-week, multicenter, double-blind, vehicle-controlled, parallel-group, phase 3b study of calcipotriene foam, 0.005% (NCT01139580). Primary end point was the proportion of subjects with an Investigator's Static Global Assessment (ISGA) score of 0 (clear) or 1 (almost clear) at week 8 for scalp involvement. Body involvement, target lesion score, and improvement for erythema, scaling, and plaque thickness were also assessed.
RESULTS: At week 8, more subjects in the calcipotriene foam, 0.005% group (40.9%) met the primary end point vs the vehicle foam group (24.2%; intent-to-treat [ITT] population; P<.001); a significant difference between groups was also observed at weeks 2 (P=.041) and 4 (P<.001). No significant difference was observed between treatment groups for ISGA of body psoriasis (ITT population; P=.544). In the per-protocol population, but not the ITT population, more subjects in the calcipotriene foam, 0.005%, group than the vehicle foam group met the secondary end points for scaling (P=.019) and plaque thickness (P=.027). Incidence of adverse events in both treatment groups was low; calcipotriene foam, 0.005%, was associated with erythema. Limitations: An 8-week study provides limited safety and efficacy data.
CONCLUSION: Calcipotriene foam, 0.005%, was more effective than vehicle foam for improving scalp psoriasis over an 8-week period, with improvements evident from week 2, and had a similar safety profile to vehicle foam.

J Drugs Dermatol. 2013;12(3):300-306.

Psoriasis causes significant distress and impairment in health-related quality of life (QOL) in afflicted patients. For this reason, QOL is an essential and important measure of treatment outcome in patients with the disease. Clobetasol propionate is a super-highpotent class I topical corticosteroid. The spray formulation is approved for twice-daily use for up to 4 weeks by patients 18 years and older with moderate to severe plaque psoriasis. Data collected from 2,236 patients enrolled in 5 clinical trials demonstrate consistent improvement in QOL measures using multiple instruments. In a randomized, double-blind trial in patients with scalp psoriasis, treatment with clobetasol propionate 0.05% spray produced significantly greater improvement in QOL compared with vehicle, as measured by the Scalpdex QOL instrument. In another randomized trial in patients with moderate to severe plaque psoriasis, clobetasol propionate 0.05% spray produced significantly greater reductions in mean affected body surface area and significantly greater improvements in QOL, as measured by the Dermatology Life Quality Index (DLQI), compared with a 0.05% foam formulation. When compared with calcipotriene/betamethasone dipropionate ointment, clobetasol propionate 0.05% spray produced greater rates of lesion clearance and similar improvement in QOL scores after 2 or 4 weeks of treatment. When clobetasol propionate 0.05% spray was used as monotherapy or as an add-on therapy for 4 weeks in a large, observational trial, approximately 80% of patients experienced consistent and significant improvement in QOL on 2 separate, validated QOL instruments (DLQI and the Koo-Menter Psoriasis Index). In conclusion, clobetasol propionate 0.05% spray is an efficacious and safe treatment for plaque psoriasis and produces significant improvement in QOL for affected patients.

J Drugs Dermatol. 2012;11(11):1348-1354.

BACKGROUND: The Physician Global Assessment and Body Surface Area (PGAxBSA) composite tool is a simple, effective alternative for measuring psoriasis severity. OBJECTIVE: To evaluate the product of PGAxBSA as a sensitive alternative to the Psoriasis Area and Severity Index (PASI) for assessing disease severity and therapeutic response with data collected from the phase 3 ESTEEM 1 and 2 trials. METHODS: This post hoc analysis included 836 patients randomized to apremilast 30 mg BID at baseline (ESTEEM 1, n=562; ESTEEM 2, n=274). Spearman correlation coefficients were used to compare PGAxBSA, PASI, and the Dermatology Life Quality Index (DLQI). Concordance between PGAxBSA and PASI was evaluated for 50%/75%/90% improvement from baseline at week 16. RESULTS: In ESTEEM 1 and 2, PGAxBSA and PASI exhibited significant positive correlations for measuring disease severity at baseline (r≥0.757) and week 16 (r≥0.807). At week 16, ≥79% concordance was observed between PGAxBSA and PASI for 75% and 90% improvement from baseline; greater concordance (>88.0%) was observed using 50% improvement from baseline. At week 16, PGAxBSA and PASI were moderately correlated with DLQI. Limitations: Analysis was limited to patients with baseline BSA ≥10% and static PGA ≥3. CONCLUSIONS: In patients with moderate to severe psoriasis, PGAxBSA is correlated with PASI and sensitive to therapeutic response.

J Drugs Dermatol. 2017;16(2):147-153.

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Tumor necrosis factor (TNF)-α inhibitors have been shown to increase the risks of overall infection and serious infection in rheumatoid arthritis. However, it is uncertain whether we can draw the same conclusion in the psoriatic population. This article focuses on the 3 most commonly used TNF-α inhibitors in psoriasis: adalimumab, etanercept, and infliximab. In order to assess the risks of overall infection and serious infection in patients with psoriasis, we reviewed the underlying mechanism of the potential infection risk, different types of serious infection associated with TNF-α inhibitors, and current evidence in the psoriatic population. Results from 11 randomized controlled trials and open-label extension studies showed that there was no apparent significant association between the use of TNF-α inhibitors and increasing risks of overall infection and serious infection. Becasue of the limitations of current evidence, large, long-term follow-up studies with appropriate control groups using real-life data, such as postmarket surveillance, are warranted.

J Drugs Dermatol. 2013;12(3):e41-e45.

BACKGROUND: There are few studies analyzing the behavior of ustekinumab in the complex management of psoriasis within diary clinical practice setting.
OBJECTIVE: To assess the utility of ustekinumab in a psoriasis unit.
METHODS: Analysis of the prospective data gathered during the follow-up of 30 consecutive psoriasis patients treated with ustekinumab at a single referral centre. Three effectiveness endpoints were defined 12 weeks, 28 and “long-term treatment”. The main outcome measure was improvement from baseline PASI at week 28 and at a point of adjustment of prolonged treatment signed as “long-term treatment”.
RESULTS: Overall 82.1% and 42.8% patients achieved respectively PASI75 and PASI90 response rates at week 28. Long-term treatment maintained efficacy outcomes 81.5% and 40.7% PASI75 and PASI90, respectively were observed. At week 28, patients naïve to TNFα- blockers agents and patients with a baseline PASI >10 had better PASI75 and PASI90 response rates than previously treated patients.
CONCLUSIONS: In clinical practice, the efficacy and patient adherence to ustekinumab are excellent and even better to the data obtained in clinical trials. Clinical indicators of psoriasis severity: previous treatments with tumor necrosis factor α blockers agents and active treatment beside small increases in PASI determine a delayed maximal response.

J Drugs Dermatol. 2014;13(8):971-974.

Background: Fiber-optically targeted ultraviolet B (UVB) therapy has been shown to clear plaques of psoriasis in a significantly fewer number of treatments and reduce overall cumulative UVB dose than traditional UVB phototherapy. Objective: This article reviews existing theories in the literature attempting to explain the superior efficacy of targeted UVB. Methods: Medline was used to perform a comprehensive review of the literature from 1965 to present. Only information from the English language journals are reported in this study. Results: The theories proposed to explain the higher efficacy of the excimer (XeCl) laser relative to traditional UVB include the ability to use higher intensities of ultraviolet (UV) light and a more efficient induction of T cell apoptosis. Conclusion: The possible explanations for the superior efficacy of the excimer laser over traditional UVB therapy for psoriasis include: 1) a higher intensity UV light to plaques, which is more effective in clearing psoriasis; 2) penetration into the dermis where it may induce T cell apoptosis, potentially to a greater extent than the wavelength or given energy level predicts; and 3) the difference in the delivery of UVB light may result in cell death and skin immune system suppression more effectively than traditional UVB.

Psoriasis is a chronic autoimmune condition that affects over 7 million Americans, approximately 1–3 percent of the population. Although there are a number of treatment options currently available, little is known about the treatment patterns of patients. Using data from 1,006 psoriasis sufferers, the aim of the present study was to analyze patients’ treatment timeline, as well as their perceptions about these treatments. Most respondents were white, female and had health insurance. The results suggested that over-the-counter (OTC) and prescription topicals were the most common initial treatments, but systemic orals and biologics were the most common treatments for patients who required a third-line or fourth-line treatment (and for patients with greater severity). Treatment dissatisfaction was relatively high, with very few positive attributes associated with the current treatment options. Overall, this study suggests that treatment options vary (at a statistically significant level) as a function of severity, and many patients, despite the choices in the number and quality of treatment options, are generally dissatisfied.

BACKGROUND: Lower socioeconomic status is associated with poorer overall health outcomes. However, few studies have examined the impact of socioeconomic status on psoriasis.
OBJECTIVE: To examine the impact of individual socioeconomic status on systemic therapeutic outcomes amongst psoriasis patients.
METHODS: The study analyzed 156 psoriasis patients treated at the Tufts Medical Center Department of Dermatology from 2008-2014. Individual socioeconomic status was inferred from neighborhood income, defined as the percentage of households with income below the federal poverty line (% below FPL) in the patient’s census tract. The following outcomes were compared between socioeconomic groups: improvement in simple measure for assessing psoriasis activity (S-MAPA) score at 12 weeks, primary and secondary drug failure rates, and incidence of documented medication non-adherence.
RESULTS: Those patients living in relatively poorer neighborhoods (% below FPL ≤10%) experienced a significantly decreased improvement in S-MAPA score at 12 weeks of biologic treatment when compared to those in relatively richer neighborhoods (% below FPL >10%), 23.2% vs. 45.5%, P=0.021. Patients living in poorer neighborhoods also had a significantly higher rate of primary drug failure when treated with biologics (34.7% vs. 18.4%, P=0.039) and were significantly more likely to have ≥1 documented instance of medication non-adherence when treated with biologics (45.5% vs. 8.8%, P<0.001).
LIMITATIONS: Retrospective design, small sample size
CONCLUSIONS: Our study offers preliminary data that suggests lower socioeconomic status may be associated with decreased clinical response to the biologic agents, presumably through decreased medication adherence.

J Drugs Dermatol. 2016;15(2):147-153.

BACKGROUND: Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi).
OBJECTIVE: To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment.
METHODS: This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had ≥ 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment.
RESULTS: Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S-MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure.
CONCLUSIONS: Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities.

J Drugs Dermatol. 2015;14(8):893-898.

Background/Objectives: A combination topical suspension/gel containing calcipotriene plus betamethasone dipropionate has been developed as a safe and effective treatment for patients with psoriasis vulgaris of the scalp. This same preparation has the potential to be a convenient, effective, and cosmetically appealing formulation for psoriasis on the body. This trial evaluated the efficacy and safety of a topical suspension containing calcipotriene plus betamethasone dipropionate compared with its constituent components and topical suspension vehicle in the treatment of mild to moderate psoriasis on the trunk and limbs.
Methods: This was a randomized, double-blind, vehicle-controlled, 4-arm trial in 1,152 subjects. The co-primary efficacy end points were the proportion of subjects achieving controlled disease based on the Investigators' Global Assessment of disease severity at weeks 4 and 8. Adverse events, vital signs, and clinical laboratory measurements were also assessed.
Results: At week 4, a greater proportion of subjects in the calcipotriene plus betamethasone group achieved controlled disease compared with subjects in the calcipotriene-only and vehicle-only treatment groups. At week 8, a statistically significantly (P<.01) greater proportion of subjects in the calcipotriene plus betamethasone group achieved controlled disease compared with subjects in the 3 other treatment groups. Adverse events and other safety assessments were similar between the groups.
Conclusion: The topical suspension containing calcipotriene plus betamethasone dipropionate traditionally used for scalp psoriasis is also a safe and effective once-daily treatment for psoriasis vulgaris on the body.

J Drugs Dermatol. 2013;12(1):92-98.

Background: The efficacy of biologic agents to treat psoriasis has been established in well-designed clinical trials. The primary endpoint is usually a 75% reduction from the baseline Psoriasis Area and Severity Index, stressing acute control of symptoms. Another important endpoint is remission, or duration of response off therapy, which reduces exposure to immunosuppressive agents and potentially lowers costs. Methods:We searched the literature for randomized controlled clinical trials of remission with biologic agents. Results and Conclusions: Among approved biologic agents, alefacept produced the longest posttreatment clinical benefits in responders (7 to 8.6 months after a 12-week course), followed by infliximab (4.7 months after a 6-week, 3-dose induction period), etanercept (2.8 to 3.5 months after 12 weeks of therapy), and efalizumab (2.8 months after 24 weeks of therapy). Long-term response to infliximab in some patients may be limited by neutralizing antibodies. Additional data on adalimumab are needed.

Background: Moderate to severe psoriasis is a significant inflammatory disease that frequently requires systemic therapies to effectively treat the underlying disorder. Etanercept and narrow-band ultraviolet light B (NB-UVB) are widely used to treat this disease.

Objective: To evaluate the effectiveness, tolerability, and patient-reported outcomes of combination etanercept plus NB-UVB phototherapy in moderate to severe plaque psoriasis.

Methods: This 12-week, single-arm, open-label study evaluated the combination of etanercept 50 mg twice weekly and NB-UVB thrice weekly in 86 patients. The primary outcome measure was ≥75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75). Other measures included PASI 90, PASI 100, and the Dermatology Life Quality Index (DLQI).

Results: At week 12, 26.0% achieved PASI 100, 58.1% achieved PASI 90, and 84.9% of patients achieved PASI 75. Mean improvement from baseline in DLQI was 84.4%. No unexpected, untoward adverse events were noted.

Conclusions: A 12-week course of etanercept plus NB-UVB phototherapy was well tolerated and produced clinically meaningful improvements in signs and symptoms of moderate to severe plaque psoriasis and in patient-reported outcomes. Further investigation of the safety and efficacy of the use of such combination for this indication in controlled clinical trials would be of interest.

BACKGROUND: Salicylic acid is a topical keratolytic agent used to reduce scaling and hyperkeratosis associated with psoriasis vulgaris. However, its use is limited due to potential systemic toxicity. Hydroxyacids also modulate keratinization and desquamation. Therefore, they may serve a beneficial role in the treatment of hyperkeratotic conditions. To date, there are no clinical studies in the literature regarding the efficacy of hydroxyacids for psoriasis treatment.
PURPOSE: To evaluate the therapeutic efficacy of topical 20% alpha-hydroxy/polyhydroxy acid versus standard salicylic acid to reduce scaling in patients with moderate, chronic psoriasis.
METHODS: Twenty-five subjects with moderate, chronic psoriasis were enrolled in a 2-week, double-blind, left-right, randomized, bilateral comparison clinical trial to compare the efficacy of 20% alpha-hydroxy/polyhydroxy acid emollient versus 6% salicylic acid cream and 24 were randomized/completed. Clinical evaluations to assess the severity of psoriasis and scaling were performed using a 6-point scale prior to treatment, as well as following 1 and 2 weeks of therapy.
RESULTS: Twenty-four participants completed the study. Both 20% alpha-hydroxy/polyhydroxy acid emollient and 6% salicylic acid cream were efficacious in reducing scale of psoriatic lesions. The topical 20% alpha-hydroxy/polyhydroxyacid reduced scaling at a faster rate; however, following 2 weeks of treatment the efficacy of both products were relatively the same.
CONCLUSION: 20% alpha-hydroxy/polyhydroxyacid is as efficacious as salicylic acid in regards to the de-scaling of psoriatic plaques. Additionally, 20% alpha-hydroxy/polyhydroxyacid cream may yield quicker results and less toxicity than salicylic acid.

J Drugs Dermatol. 2013;12(8):855-859.

Background: Efalizumab therapy and narrow-band ultraviolet B (NB-UVB) phototherapy have different mechanisms of action; com- bined therapy may be more effective than either treatment alone in treating moderate to severe plaque psoriasis.
Methods: This study investigated the effi cacy and safety of efalizumab (1 mg/kg/wk) combined with NB-UVB 3 times a week for 12 weeks, followed by efalizumab monotherapy for 12 additional weeks.
Results: Twenty patients were enrolled with mean Psoriasis Area and Severity Index (PASI) of 12.8±7.4, mean physician’s global assessment (PGA) of 5±1, and mean body surface area (BSA) affected of 18.2%±15.3% at baseline. At week 12, 65% of patients (n=13) achieved PASI 75; mean PGA was 2±1, corresponding to a 60% reduction; and mean BSA was 4.7%±4.1%, corresponding to a 74% reduction. The improvements seen at week 12 were maintained during the ensuing efalizumab monotherapy.
Conclusion: Combination of efalizumab and NB-UVB followed by efalizumab monotherapy was effective and well tolerated, this warranting further investigation.

We present a case of a 36-year-old man with a 20-year history of stable plaque psoriasis admitted to our inpatient dermatology unit with subacute annular pustular psoriasis. Two weeks prior to admission the patient’s dermatologist discontinued the use of 5 lbs (2.3 kg) of triamcinolone 0.1% cream, which the patient had been applying to his skin weekly over the last 8 years. The patient subsequently developed generalized erythematous annular and irregularly shaped, well-defined plaques and confluent pustules. Approximately 80% of his total body surface area was involved, sparing the face and the genitals. Initial therapy included cyclosporine 300 mg twice daily, topical hydrocortisone 1% ointment to affected areas, acetaminophen/oxycodone 10/325 mg every 4 hours for pain as needed, and subcutaneous etanercept 50 mg twice weekly. The patient was discharged on day 7 with significant improvement of skin lesions. On discharge the cyclosporine was increased to 400 mg twice daily. The patient continued etanercept 50 mg twice weekly. One month after discharge the patient was clear with only postinflammatory changes

Efalizumab is an immunosuppressive agent that has been approved for the treatment of psoriasis. There has been mounting evidence that efalizumab may be associated with lymphoma/malignancy development. To our knowledge, this is the first documented case of a patient who developed Epstein Barr Virus-associated large B cell lymphoma after treatment with efalizumab for psoriasis. As immunosuppressive medications such as efalizumab get increasingly prescribed, the likelihood of seeing various malignancies will increase. Thus, physicians need to have a high index of suspicion for malignancy in patients on immunosuppressive medications like efalizumab.

BACKGROUND: A novel lotion formulation of halobetasol propionate, 0.05% (HBP Lotion) with enhanced vehicle characteristics of a cream while preserving the ease of use and cosmetic elegance of a lotion has been developed to treat plaque psoriasis. OBJECTIVE: Determine the safety and effectiveness of HBP Lotion in patients with plaque psoriasis. METHODS: Two prospective, randomized, vehicle-controlled clinical studies were conducted in 443 adult subjects with moderate-severe plaque psoriasis. Subjects applied the test article to psoriatic plaques within the treatment area twice daily for 14 days. Efficacy data are based upon treatment “success” defined as those subjects that achieved scores of 0=clear or 1=almost clear with at least a two-grade improvement relative to baseline for an Investigator’s Global Assessment (IGA) and clinical signs (plaque elevation, erythema, scaling). Safety data are presented as adverse events and local skin reactions. RESULTS: After two weeks of treatment with HBP Lotion, 44.5% of the HBP Lotion treated subjects in each study achieved (a) treatment “success” (ie, an IGA score of 0=clear or 1=almost clear and >2 grade improvement compared to baseline) and (b) a notable reduction in plaque elevation, erythema, scaling, and pruritus. In contrast, only 6.3% and 7.1% of VEH subjects in Studies 1 and 2, respectively, achieved treatment success and the reduction of disease related signs was materially lower. Statistically, at day 15 in both Phase 3 studies, treatment success with HBP Lotion was superior to VEH (P less than 0.001). From a safety perspective the outcomes were in general unremarkable with similar findings in the HBP Lotion and VEH treatment groups. CONCLUSIONS: The results demonstrate the safety and effectiveness of HBP Lotion in the treatment of plaque psoriasis. Furthermore, this novel HBP lotion formulation is also distinguished by its moisturization qualities and ease of use.

J Drugs Dermatol. 2017;16(3):234-240.

Oral retinoids are among the first line agents for treatment of pustular and erythrodermic psoriasis, and they are effective in combination with phototherapy and other topical and systemic agents for the treatment of plaque psoriasis. Acitretin is the leading oral retinoid used today for the treatment of psoriasis. Recently, possible side effects such as pseudotumor cerebri and depression have gained a warning and precaution respectively on the acitretin package insert. This paper presents a review of the scientific literature and attempts to clarify whether warnings of these side effects have arisen from a scientific evidence base or from theoretical concern/class labeling. A paucity of scientific evidence was found in this review for acitretin-associated pseudotumor cerebri and depression. The authors conclude that these 2 acitretin side effects must be further investigated to assess whether these associations are scientifically certain or if class labeling has led to inclusion in the package insert

This supplement to the Journal of Drugs in Dermatology help address various components of psoriasis and comorbidities, as well as hidradenitis suppurativa and biologic treatments. Dr. Kircik and Onumah's article covers psoriasis and its identified comorbidities or chronic proinflammatory disorders driven by similar immunopathologic expression of immune response mechanisms. Dr. Zeichner covers immunologic therapies for treatment of psoriasis-tumor necrosis factor (TNF) inhibitors and interleukin (IL)-12 and IL-23 inhibitors: etanercept, adalimumab, infliximab, golimumab, and ustekinumab. Dr. Zeichner also considers therapeutic management prior to initiating biologic therapy. Lastly, Drs. Elena Sotiriou MD PhD et al from Aristotle University in Thessaloniki, Greece provides perspectives on a prospective clinical trial of efficacy of adalimumab in the treatment of hidradenitis suppurativa. The study demonstrates the significant efficacy of the once weekly regimen, as well as its benefit regarding time to recurrence.

Induced psoriasiform eruption, especially by anti-tumor necrosis factor alpha, was a rather rare event but nowadays cases are increasing because of its prescription for many different diseases. There are several clinical forms; one example is the pustulosis form presented in this case report.

J Drugs Dermatol. 2015;14(10):1152-1154.

BACKGROUND: Calcipotriol is a newer topical treatment option available for plaque psoriasis and coal tar being one of the oldest treatment and still in use.
AIMS: To evaluate and compare the differences in terms of efficacy, safety and relapse with Calcipotriol 0.005% (50 mcg/gm) and 6% coal tar and 3% salicylic ointment in patients with Plaque psoriasis.
SETTING and DESIGNS: Study conducted on 60 patients of plaque psoriasis, who attended the skin OPD in our hospital.
METHODS: The patients with mild to moderate plaque psoriasis were selected. 60 patients were enrolled for the study after obtaining informed consent. Subjects were asked to apply Calcipotriol 0.005% (50 mcg/gm) (Heximar Win care) twice a day on the right side plaques and on left side plaques, Petroleum jelly (Vaseline) in the morning and 6% coal tar and 3% salicylic ointment (Protar® Percos) at nighttime. PASI score was used to assess the reponse to therapy at 2nd, 4th, 6th and 8th week. After treatment subjects were observed for 6 weeks for any relapse.
STATISTICAL ANALYSIS: It was done by paired t-test and independent sample t-test.
CONCLUSIONS: The results showed that statistically significant difference was seen in the mean percentage reduction of PASI score between both the groups, at all the assessment visits, 2, 4, 6, and 8 weeks, the mean percentage reduction at 2 weeks for calcipotriol being 21±12.06 and for coal tar being 13.44±11.19 (P=0.000), at 4 weeks for calcipotriol was 40±16.71 and for coal tar 25±99 (P=0.000), at 6 weeks for calcipotriol was 53.99+-22.43 and for coal tar 41±21.23 (P=0.002), at 8 weeks for calcipotriol was 62.73±24.04 and for coal tar was 51.53±23.27 (P=0.11). Relapse was seen in 5/60 (8.3%) of patients on calcipotriol treated side and 9/60 (15%) of patients with coal tar treated side. Thus it can be concluded that calcipotriol cream is more efficacious when compared with coal tar and does have a quick response. It is well tolerated and acceptable cosmetically.

J Drugs Dermatol. 2013;12(8):868-873.

Background: 308 nm excimer laser phototherapy is efficacious in the treatment of localized psoriasis. Different approaches regarding dose fluency, number of treatments, and maintenance have been utilized, and there is yet to be a consensus on standard protocol.
Objective: To characterize treatment parameters for 308 nm excimer laser phototherapy.
Methods: We performed a PubMed search for studies describing excimer laser treatment protocol with particular attention to dosage determination, dose adjustment, dose fluency, number of treatments, and maintenance.
Results: Seven prospective studies were found describing the excimer efficacy for psoriasis. All studies determined the initial treatment dose using either the minimal erythema dose (MED) or induration. Fluency ranged from 0.5 MED (low) to 16 MED (high); one study demon- strated that medium to high fluencies yielded better improvement in fewer number of treatments. Fluency adjustments during the course of treatment were important to minimize phototherapy-associated side effects. The use of higher fluencies was reported to result in higher occurrences of blistering. One study implemented a maintenance tapering of dose-frequency phase to better manage psoriasis flare-ups.
Conclusion: The 308 nm excimer laser is an effective therapy for psoriasis regardless of the method used to determine initial dosage, dose fluency, or number of treatments. As its usage as a targeted monotherapy increases, future trials should consider evaluating and modifying these parameters to determine the most optimal management of localized psoriasis. Based on our reviewed studies, there is no consensus for a single excimer laser therapy protocol and as a result, patient preferences should continue to be an important consid- eration for phototherapy regimen planning.

J Drugs Dermatol. 2012;11(1):92-97.

Background: Alefacept has an established efficacy and safety profile for 12 weeks of treatment of severe chronic plaque type psoriasis. The effectiveness and safety of longer-term continuous use is not well characterized. Methods: Fifteen subjects with moderate-to-severe chronic plaque type psoriasis were given weekly 15 mg alefacept injections for 16 consecutive weeks followed by monthly 15 mg injections for up to eight consecutive months, along with clobetasol propionate spray 0.05% twice daily for the first four weeks. Disease severity was measured using the Psoriasis Area and Severity Index (PASI) and the Investigator Global Assessment (IGA). Results: Mean PASI scores improved 33 percent overall during the first month with combination treatment. There was an overall 21 percent worsening in PASI scores after the transition from weekly to monthly medication administration. Of the 15 initially enrolled patients, 27 percent achieved PASI 75 by end of study. No patients achieved an IGA of 0 or 1 by end of study. Two major adverse events were reported: low CD4 count and severe allergic dermatitis. Conclusion: Topical clobetasol propionate 0.05% was only partially effective at augmenting the early treatment effect of alefacept. The authors did not observe marked benefit or major side effects by continuing additional monthly alefacept treatments beyond 16 weeks of weekly treatment.

BACKGROUND: Many patients with moderate plaque psoriasis are undertreated despite broadening treatment options. In the phase IV UNVEIL study, oral apremilast demonstrated efficacy and safety in systemic-naive patients with chronic moderate plaque psoriasis with lower psoriasis-involved body surface area (BSA; 5%–10%) during the 16-week, double-blind, placebo-controlled phase. We describe efficacy and safety of apremilast in this population through week 52 in UNVEIL.

METHODS: Patients with moderate plaque psoriasis (BSA 5%–10%; static Physician’s Global Assessment [sPGA] score of 3 [moderate]) and naive to systemic therapies for psoriasis were randomized (2:1) to receive apremilast 30 mg twice daily or placebo for 16 weeks. At week 16, patients continued on apremilast (apremilast/apremilast) or were switched from placebo to apremilast (placebo/apremilast) through week 52 (open-label apremilast treatment phase). Efficacy assessments included the product of sPGA and BSA (PGAxBSA) (mean percentage change from baseline; ≥75% reduction from baseline [PGAxBSA-75]), sPGA response (achievement of score of 0 [clear] or 1 [almost clear]), and the Dermatology Life Quality Index (DLQI; mean change from baseline).

RESULTS: A total of 136 patients completed the 52-week analysis period (placebo/apremilast, n=50/64; apremilast/apremilast, n=86/121). At week 52, improvements in all efficacy end points observed at week 16 were maintained in the apremilast/apremilast group (mean percentage change from baseline in PGAxBSA: −55.5%; PGAxBSA-75: 42.1%; sPGA response: 33.1%; mean change from baseline in DLQI score: −4.4); similar improvements emerged in the placebo/apremilast group after switching to apremilast. The most common adverse events (≥5% of patients) through week 52 were diarrhea (28.0%), nausea (19.0%), headache (15.2%), nasopharyngitis (10.4%), upper respiratory tract infection (7.1%), vomiting (5.7%), and decreased appetite (5.2%).

CONCLUSIONS: Apremilast was effective in systemic-naive patients with moderate plaque psoriasis with BSA 5%–10%; efficacy was sustained through week 52. No new safety signals emerged with continued apremilast exposure.

ClinicalTrials.gov: NCT02425826

J Drugs Dermatol. 2018;17(2):221-228.

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Clobetasol propionate is known to be a very effective treatment for psoriasis; however, its use is limited by potent corticosteroid class related side effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression and atrophogenicity. The aim of this single-center, parallel group, randomized study was to assess the HPA axis suppression potential, atrophogenicity, and ocular tolerability of clobetasol propionate shampoo in 26 patients with scalp psoriasis. Suitable subjects were treated once daily for 4 weeks with clobetasol propionate shampoo, to be rinsed off after 15 minutes or with a leave-on clobetasol propionate gel. The study demonstrated that clobetasol propionate shampoo did not lead to HPA axis suppression or to skin atrophy. Conversely, the gel led to HPA axis suppression and a decrease in skin thickness. Neither formulation had an impact on ocular safety. Despite the short contact application time, the clobetasol propionate shampoo provides similar efficacy results to the gel.

Over a decade ago, the FDA approved biologics for psoriasis, which changed how the disease is treated and, in most cases, has a significant positive impact on the lives of patients. Side effects primarily identified during the investigational and research phase led to the development of specific guidelines for treatment. The treatment guidelines have been amended to incorporate better understandings of side-effects over the years that the disease has been treated. In this study, we focused on a chart review that included assessing the current guidelines and their alignment with modern patient management and the recent side effects presented. This life-cycle evaluation included over 100 patients, management of their treatment, laboratory abnormalities, criteria for choosing or changing to a different biologic, and the effects of the treatments management throughout the years. The review identified some recommended changes in the application and treatment of psoriasis with biologics. To further evidence our findings, we hope to expand this study to a larger scale with more patients.

J Drugs Dermatol. 2017;16(3):215-217.

Infliximab, a novel chimeric anti-tumor necrosis factor-α (TNF-α) monoclonal antibody, has been increasingly used in the treatment of pyoderma gangrenosum. However, an established dosing regimen is lacking in the published literature. A variety of dosing regimens have been suggested, including a treatment schedule similar to that of psoriasis. The authors report a case of rapid response to infliximab in a patient with pyoderma gangrenosum associated with inflammatory bowel disease utilizing a dosing regimen similar to that used for psoriasis.

INTRODUCTION: Tofacitinib is a novel, oral Janus kinase inhibitor currently under investigation for plaque psoriasis.
METHODS: This exploratory analysis of a Phase IIb, 12-week, dose-ranging study (clinicaltrials.gov identifier: NCT00678210) evaluated tofacitinib efficacy in four body regions of patients with moderate-to-severe chronic plaque psoriasis. Patients (n=197) were randomized to tofacitinib 2, 5, or 15 mg, or placebo, twice daily (BID). Psoriasis Area and Severity Index (PASI) score, body surface area values and change from baseline to week 12 were measured according to body region (head/neck, upper limbs, trunk and lower limbs). Change in Target Plaque Severity Score (TPSS) from baseline to week 12 was measured according to typically responsive as well as non-responsive treatment areas.
RESULTS: At week 12, mean improvements in PASI and body surface area values were significantly greater with tofacitinib doses vs placebo across all four body regions measured (P<0.0001). TPSS in responsive areas decreased (improved) with tofacitinib 2, 5, and 15 mg BID vs placebo: -4.35, -4.79 and -6.32, vs -2.06, respectively (P<0.0001). In non-responsive areas, TPSS decreased with tofacitinib 2, 5, and 15 mg BID vs placebo: -3.74, -4.60 and -6.15, vs -2.23, respectively (P<0.01).
CONCLUSION: Short-term (12-week) treatment with oral tofacitinib produced clinical improvement across all body regions assessed in patients with moderate-to-severe plaque psoriasis, including areas typically non-responsive to treatment.

J Drugs Dermatol. 2014;13(3):252-256.

BACKGROUND: Psoriasis is a debilitating skin disease associated with substantial pruritus, work impairment, and sleep disturbance.
OBJECTIVE: This study evaluated associations between pruritus and work productivity, and the role of sleep problems as a possible mediator of the relationship between the two.
METHODS AND MATERIALS: Data from a pruritus visual analog scale (Itch VAS), the Medical Outcomes Study Sleep Scale (MOS-SS), and the Work Productivity and Activity Impairment Questionnaire (WPAI) were collected in a phase 2 clinical trial in patients with psoriasis treated with ixekizumab or placebo. Mediating effects of sleep were tested in multiple regressions with pruritus severity (independent variable) and work productivity (dependent variable). Sobel tests evaluated the significance of sleep’s effect.
RESULTS: Several MOS-SS domains were significantly associated with the WPAI presenteeism, work productivity, and activity impairment scores, and decreased the effect of pruritus. Sobel tests indicated that the Sleep Problems Index I had a significant effect (P<.05) in mediating the relationship between pruritus and presenteeism, work productivity, and activity impairment.
CONCLUSION: Sleep may mediate the role of pruritus on work productivity, but both factors appear to have independent negative effects on work.

J Drugs Dermatol. 2016;15(2):183-188.

Topical corticosteroids and vitamin D analogs are well established as safe and effective first-line treatments for mild to moderate plaque psoriasis. They act via distinct and complementary mechanisms of action: vitamin D analogs primarily counter epidermal dysregulation, inhibiting epidermal hyperproliferation and inducing keratinocyte differentiation, whereas corticosteroids act primarily as immunosuppressors, targeting pro-inflammatory cytokines and chemokines. Furthermore, both agents have additional activity that may complement their main effects: vitamin D analogs have some immunomodulatory properties and corticosteroids may impact on keratinocyte differentiation. Based on their dominant mechanisms of action, there is a strong scientific rationale for the combination of corticosteroids and vitamin D analogs in the treatment of plaque psoriasis. Indeed, the combination has been shown to have a greater effect on the immune-mediated mechanisms of psoriasis than either monotherapy used alone. There is also a strong biological rationale for decreased side effects with the combination. Vitamin D may restore epidermal barrier function, which is impaired with corticosteroid use, and counteract steroid-induced skin atrophy. Corticosteroids may reduce perilesional skin irritation induced by vitamin D analogs. Although clinical data strongly support improved efficacy and tolerability with a combination of calcipotriol and betamethasone dipropionate, additional studies are needed to further investigate their underlying mechanisms.

J Drugs Dermatol. 2013;12(8):e129-e137.

No abstract details for the moment.

Background: There is limited research exploring patient preferences regarding dosing frequency of biologic treatment of psoriasis. Methods: Patients with moderate-to-severe plaque psoriasis identified in a healthcare claims database completed a survey regarding experience with psoriasis treatments and preferred dosing frequency. Survey questions regarding preferences were posed in two ways: (1) by likelihood of choosing once per week or 2 weeks, or 12 weeks; and (2) by choosing one option among once every 1-2 or 3-4 weeks or 1-2 or 2-3 months. Data were analyzed by prior biologic history (biologic-experienced vs biologic-naïve, and with one or two specific biologics). Results: Overall, 426 patients completed the survey: 163 biologic-naïve patients and 263 biologic-experienced patients (159 had some experience with etanercept, 105 with adalimumab, and 49 with ustekinumab). Among patients who indicated experience with one or two biologics, data were available for 219 (30 with three biologics and 14 did not specify which biologic experience). The majority of biologic-naïve (68.8%) and overall biologic-experienced (69.4%) patients indicated that they were very likely to choose the least frequent dosing option of once every 12 weeks (Table 1). In contrast, fewer biologic-naïve (9.1% and 16.7%) and biologic-experienced (22.5% and 25.3%) patients indicated that they were very likely to choose the 1-week and 2-week dosing interval options, respectively. In each cohort grouped by experience with specific biologics, among those with no experience with ustekinumab, the most chosen option was 1-2 weeks. The most frequently chosen option was every 2-3 months, among patients with any experience with ustekinumab, regardless of their experience with other biologics. Conclusions: The least frequent dosing interval was preferred among biologic naïve patients and patients who had any experience with ustekinumab. Dosing interval may influence the shared decision-making process for psoriasis treatment with biologics.

J Drugs Dermatol. 2017;16(3):220-226.

BACKGROUND: Psoriasis is associated with increased risk of major adverse cardiovascular events (MACE). OBJECTIVES: Compare MACE risk with biologics vs topical/phototherapy use. METHODS: Psoriasis Longitudinal Assessment Registry (PSOLAR) is an international psoriasis registry of patients eligible to receive biologic/systemic treatments prospectively. MACE is defined as myocardial infarction, stroke, or cardiovascular death. Biologic cohorts, including tumor necrosis factor-alpha (TNF-α) inhibitors (ie, adalimumab, etanercept, and infliximab) and ustekinumab, combined and by class, were compared with a topical/phototherapy cohort. Incidence rates of MACE per 100-patient-years (100PY) with 95% confidence intervals (95% CI) are reported. Multivariate analyses were performed to evaluate the effect of treatment on the risk of MACE adjusting for confounders. RESULTS: Analyses included 7550 patients: 6767 in the combined biologics cohort (3949 and 2818 in the TNF-α inhibitors and ustekinumab cohorts, respectively) and 783 in the topical/phototherapy cohort. Mean duration of exposure was approximately 2.8 years (combined biologics) and 4.1 years (topical/phototherapy). A total of 52 MACE were reported; MACE incidence rates were 0.22/100PY (95% CI: 0.16, 0.30) for the combined biologics cohort (TNF-α inhibitors [0.20/100PY (0.12, 0.31)] and ustekinumab [0.24/100PY (0.15, 0.37]) and 0.34/100PY (0.17, 0.61) for the topical/phototherapy cohort. For the combined biologics (hazard ratio=0.92; 95% CI [0.426, 1.988]), TNF-α inhibitor (0.85 [0.373, 1.928]), and ustekinumab (1.03[0.440, 2.402]) cohorts, treatment was not associated with increased risk of MACE versus the topical/phototherapy cohort. CONCLUSION: Based on data accumulated to date in PSOLAR, treatment with biologics did not have an impact on the risk of MACE in patients with moderate-to-severe psoriasis.

J Drugs Dermatol. 2017;16 (10):1002-1013.

Introduction: Psoriasis is one of several systemic diseases that presents chiefly with cutaneous symptoms and has the potential to negatively impact patients' overall health and quality of life. Physicians who treat patients with psoriasis must be cognizant of the chronic, lifelong character of the disease and of the potential for multisystem pathology. According to the National Institutes of Health (NIH), between 5.8 and 7.5 million persons in the U.S.-approximately 2.2% of the population-have psoriasis; worldwide, it affects an estimated 125 million people. The annual cost of treating psoriasis may exceed $3 billion annually. Immunologic mechanisms are now accepted as the pathophysiologic basis for the development of psoriatic disease. Treatment strategies-which include topical treatment, phototherapy, methtrexate, cyclosporine and acitretin-also encompass several biologic agents that target immune mediators associated with the condition.
Discussion: Patients with mild disease may obtain symptomatic relief with topical agents and targeted phototherapy. Patients with moderate-to-severe disease are likely to benefit from systemic therapy. Shortcomings of the traditional agents, particularly their adverse event profiles, have motivated research and development of biologic agents. Currently three anti-TNF agents - etanercept, infliximab and adalimumab - are FDA-approved for treatment of psoriasis. Differences exist among study designs and, therefore, in interpretation of data; however, the improvements observed in the psoriasis study populations participating in clinical trials are dramatic. Long-term clinical data continue to accumulate and demonstrate sustained benefits with anti-TNF agents. Safety data also continue to be collected over the long-term; key safety considerations are infection, cytopenia, demyelinating disease, lupus-like syndromes, congestive heart failure and malignancies. Combination therapy should also be considered when managing psoriasis for such reasons as augmenting an inadequate response to monotherapy or improving tolerability. Combination therapy with an anti-TNF agent and phototherapy has shown considerably higher rates of response compared with either intervention alone.
Objective: The objective of this paper is to critically examine the anti-TNF studies to assess the efficacy and safety of the agents in patients with psoriasis and determine applicability of the data in clinical practice. In light of the chronic nature of this disease, the emphasis will be on the longest-term data available.
Conclusion: The treatment of plaque psoriasis with TNF-α antagonists is still a relatively recent addition to the pharmacologic armamentarium available to clinicians. The collection of long-term data is, therefore, small but growing as results from newer studies emerge. From the data reviewed here, the clinician can attempt to arrive at a satisfactory assessment of the benefits and risks of treatment with these agents.

BACKGROUND: Topical corticosteroids are known to impair the epidermal barrier, even after short-term use, whereas topical vitamin D analogues can have a reparative effect. Combination products using corticosteroids and vitamin D analogues have gained popularity in recent years and may provide a means to minimize skin atrophy in patients treated with topical corticosteroids.

OBJECTIVE: To compare epidermal barrier function and cutaneous atrophy after 4 weeks of calcipotriene 0.005% and betamethasone dipropionate 0.064% topical suspension (Taclonex® TS) versus betamethasone dipropionate 0.05% lotion (Diprosone®).

METHODS: Ten subjects with moderate plaque psoriasis were enrolled. Patients were randomized to apply calcipotriene 0.005%/betamethasone dipropionate 0.064% once daily to psoriasis plaques on one side of the body and betamethasone dipropionate 0.05% lotion twice daily to plaques on the other side. Biopsies were performed at baseline and after four weeks of treatment to evaluate for epidermal and dermal changes.

RESULTS: Treatment with betamethasone lotion resulted in significant decreases in epidermal thickness and dermal thickness. In contrast, treatment with calcipotriene/betamethasone did not lead to significant decreases in epidermal thickness or dermal thickness. Comparing betamethasone and calcipotriene/betamethasone, there was a significantly greater reduction in epidermal thickness with betamethasone lotion versus calcipotriene/betamethasone (P less than .0001). Relative differences in dermal thickness and transepidermal water loss (TEWL) did not reach statistical significance.

CONCLUSION: This study is the first to demonstrate that treatment of plaque psoriasis with a combination topical corticosteriod and calcipotriene product results in greater preservation of the skin layers relative to topical corticosteroid use alone. These results hold important ramifications for minimizing cutaneous atrophy in patients receiving treatment with topical corticosteroids.

J Drugs Dermatol. 2017;16(8):747-752.

OBJECTIVE: We sought to assess whether the type of TNF inhibitor therapy (soluble receptor versus monoclonal antibody) has an effect on MI risk; and determine whether length of TNF inhibitor therapy has an effect on MI risk.
DESIGN: Retrospective cohort study
SETTING: Between January 1, 2004 and November 30, 2010
PARTICIPANTS: At least 3 ICD9 codes for psoriasis (696.1) or psoriatic arthritis (696.0) (without antecedent MI).
INTERVENTION: None
MAIN OUTCOME MEASURE: Incident MI
RESULTS: In the 3 subgroups of TNF inhibitors, 976 received etanercept; 217 received monoclonal antibody; and 480 received etanercept or monoclonal antibody, in addition, 5075 received topical therapy and 2097 received oral therapy. In the Cox proportional hazards analysis, etanercept (HR, 0.53; 95% CI, 0.31-0.92) was associated with a significant reduction of MI risk, compared to topical agents and, monoclonal antibody only (HR, 0.25; 95% CI, 0.06-1.03), and etanercept or monoclonal antibody (HR, 0.53; 95% CI, 0.27-1.06) were associated with a non-significant reduction of MI risk compared to topical agents. Using year 1 as reference, those who received TNF inhibitor therapy at year 2 (HR, 1.15; 95% CI, 0.30-4.44), at year 3 (HR, 1.89; 95% CI, 0.64-5.58), and at year 4 and above (HR, 1.16; 95% CI, 0.46-2.94) had a non-significant increase of MI risk.
CONCLUSIONS: Treatment with etanercept, compared to treatment with topical agents, was associated with a significant decreased risk of MI in psoriasis patients. Treatment with monoclonal antibody and etanercept or monoclonal antibody, compared to treatment with topical agents, was associated with a non-significant decreased risk of MI risk in psoriasis patients. There were no statistically significant changes in risk of MI associated with length of TNF inhibitor treatment.

J Drugs Dermatol. 2013;12(8):899-903.

BACKGROUND: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate is effective and safe in the treatment of psoriasis on the body and scalp within the general psoriasis patient population.
OBJECTIVE: To evaluate the systemic effects of once-daily use of two-compound topical suspension/gel on the hypothalamic-pituitary-adrenal (HPA) axis and calcium homeostasis in subjects with extensive psoriasis vulgaris.
METHODS: An open-label, single-group, 8-week trial in 43 subjects with extensive psoriasis covering 15–30% of the body surface area. Blood and 24-hour urine samples were collected and a standard-dose adrenocorticotropic hormone (ACTH) stimulation test was performed at baseline, weeks 4 and 8. Primary endpoints were serum cortisol 30 minutes after ACTH injection (HPA axis response abnormal at serum cortisol ≤18 μg/dL) and changes from baseline in albumin-corrected serum calcium (sCa), 24-hour urinary calcium excretion (24hCa) and urine calcium:creatinine ratio (Ca:Crea).
RESULTS: Two (4.7%) subjects showed signs of adrenal suppression based on the ACTH stimulation test results at week 4; both were withdrawn from treatment and had normal serum cortisol 30-minute values at follow-up 4 weeks later. None of the subjects who continued treatment to week 8 showed signs of adrenal suppression. There were no clinically relevant mean changes from baseline to weeks 4 and 8 in sCa, 24hCa or Ca:Crea and no subject had sCa above the reference range.
CONCLUSION: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate may be applied once daily to extensive psoriasis vulgaris without generally causing adrenal suppression or disturbance of calcium homeostasis, consistent with previous findings. In a small number of patients with extensive psoriasis treated with large volumes of topical suspension, adrenal suppression may be observed. In the real-world setting, it is anticipated that systemic side-effects would occur in only a few cases within the general psoriasis patient population.

J Drugs Dermatol. 2013;12(8):882-887.
ClinicalTrials.gov Identifier: NCT 01229098

BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Treatment options focus on relieving symptoms, reducing inflammation, induration, and scaling, and controlling the extent of the disease. Topical corticosteroids are the mainstay of treatment, however long-term safety remains a concern, particularly with the more potent formulations. Combination therapy with a corticosteroid and tazarotene may improve psoriasis signs at a lower corticosteroid concentration providing a superior safety profile. OBJECTIVE: To investigate the efficacy and safety of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in comparison with its monads and vehicle in subjects with moderate-to-severe plaque psoriasis. METHODS: Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study in moderate or severe psoriasis (N=212). Subjects randomized (2:2:2:1 ratio) to receive HP/TAZ, individual monads, or vehicle, once-daily for 8 weeks. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of ‘Clear’ or 'Almost Clear'), and impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion. Safety and treatment emergent adverse events (TEAEs) were evaluated throughout. RESULTS: HP/TAZ lotion demonstrated statistically significant superiority over vehicle as early as 2 weeks. At week 8, 52.5% of subjects had treatment success compared with 33.3%, 18.6%, and 9.7% in the HP (P=0.033), TAZ (P less than 0.001), and vehicle (P less than 0.001) groups, respectively. HP/TAZ lotion was superior to its monads and vehicle in reducing the psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. At week 8, a 2-grade improvement in IGA was achieved by 54.2% of subjects for erythema, 67.8% for plaque elevation, and 64.4% for scaling. Most frequently reported TEAEs were application site reactions, and were more likely associated with the tazarotene component. Side effects such as skin atrophy were rare. CONCLUSIONS: HP/TAZ lotion was consistently more effective than its monads or vehicle in achieving treatment success and reducing psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. Safety data were consistent with the known safety profile of halobetasol propionate and tazarotene, and did not reveal any new safety concerns with the combination product.

J Drugs Dermatol. 2017;16(3):197-204.

INTRODUCTION: Many options are available for patients with moderate to severe plaque psoriasis. Patients with moderate disease, however, are often undertreated and do not achieve satisfactory clearance. UNVEIL (NCT02425826) assessed efficacy and safety of apremilast in patients with chronic moderate plaque psoriasis.

METHODS: Patients with psoriasis body surface area (BSA) 5% to 10% and static Physician’s Global Assessment (sPGA) score of 3 (moderate) without prior exposure to systemics were randomized (2:1) to apremilast 30 mg twice daily or placebo for 16 weeks. The primary efficacy endpoint was mean percentage change in the product of sPGA and BSA scores (PGAxBSA).

RESULTS: Of 221 patients (placebo, n=73; apremilast, n=148), >80% had received prior topical therapy. At week 16, apremilast yielded a significantly greater percentage change from baseline in PGAxBSA (−48.1%) vs placebo (−10.2^; P less than 0.0001). Dermatology Life Quality Index scores were significantly improved with apremilast (−4.8) vs placebo (−2.4; P=0.0008). Mean improvements in the Treatment Satisfaction Questionnaire for Medication, version II, were greater with apremilast vs placebo for global satisfaction (63.2 vs 48.7; P less than 0.0001) and treatment effectiveness (57.3 vs 38.8; P less than 0.0001). Most adverse events were mild or moderate; most common were diarrhea, headache, nausea, upper respiratory tract infection, decreased appetite, and vomiting.

CONCLUSION: Apremilast was effective and well tolerated, significantly improved quality of life, and was associated with high patient satisfaction in systemic-naive, post-topical patients with moderate plaque psoriasis.

ClinicalTrials.gov: NCT02425826

J Drugs Dermatol. 2017;16(8):801-808.

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Background: Psoriasis is a chronic skin disorder affecting approximately 2% of the US population. Psoriasis may occur anywhere on the body with initial presentation usually seen between 15 and 30 years of age. Calcitriol 3 ?g/g ointment has demonstrated good clinical efficacy as well as topical and systemic safety when used to treat psoriasis. Objectives: To confirm the efficacy and safety of calcitriol 3 ?g/g ointment versus its vehicle in the treatment of subjects with mild to moderate chronic plaque psoriasis. Methods: Suitable subjects were randomized to receive either calcitriol 3 ?g/g ointment or its vehicle twice daily for up to 8 weeks in 2 multicenter, randomized, vehicle-controlled, double-blind parallel group studies. Efficacy was evaluated through a Global Severity Score dichotomized in success (clear and minimal) or failure. Erythema, plaque elevation, scaling and dermatologic sum score (sum of the scores for erythema, plaque elevation, and scaling), pruritus, and global improvement were also assessed. Routine safety and clinical laboratory parameters, including calcium homeostasis, were evaluated throughout the study. Results: In total, 839 subjects were included in the 2 studies: 419 patients received calcitriol 3 ?g/g ointment and 420 received the vehicle. In both studies, calcitriol 3 ?g/g ointment was shown to be significantly more effective than its vehicle, with onset of therapeutic effect seen as early as week 2 and sustained at all subsequent visits. Calcitriol 3 ?g/g ointment demonstrated good systemic and local safety profile comparable to its vehicle with no effect on calcium homeostasis. Conclusion: Calcitriol 3 ?g/g ointment applied for 8 weeks is effective and safe in the treatment of mild to moderate

BACKGROUND: Safety surveillance is needed for biologic therapies for psoriasis.
OBJECTIVE: To assess the risk of adverse events of special interest (AEoSIs) with ustekinumab and other psoriasis treatments in a real-world setting using 2014 Psoriasis Longitudinal Assessment and Registry (PSOLAR) data. AEoSIs included malignancy (excluding nonmelanoma skin cancer), major adverse cardiovascular events (MACE), serious infection, and all-cause mortality.
METHODS: Cumulative rates of AEoSIs/100 patient-years (PY) are reported for ustekinumab, infliximab, other biologics (mostly adalimumab/etanercept), and non-biologics based on pre-specified analyses using attribution rules biased against ustekinumab. Risk factors for AEoSIs, including treatments, were determined using multivariate statistical analysis.
RESULTS: A total of 12,093 patients (40,388 PY) were enrolled in PSOLAR. Overall incidence rates were 0.68/100PY for malignancy, 0.33/100PY for MACE, 1.60/100PY for serious infection, and 0.46/100PY for mortality. Unadjusted rates of serious infection for infliximab (2.91/100PY) and other biologics (1.91/100PY) were numerically higher compared with ustekinumab (0.93/100PY). Exposure to the combined group of biologics other than ustekinumab was significantly associated with serious infection (hazard ratio=1.96, P<.001). None of the biologics was associated with increased risk of malignancy, MACE, or mortality.
LIMITATIONS: Observational data have inherent biases.
CONCLUSION: Analysis of 2014 PSOLAR data identified no increased risk of malignancy, MACE, serious infection, or mortality with ustekinumab.

J Drugs Dermatol. 2015;14(7):706-714.

BACKGROUND: Calcipotriene 0.005% (Cal)/betamethasone dipropionate 0.064% (BD) aerosol foam was developed as a new treatment option for patients with psoriasis. This pooled analysis evaluated the efficacy of this formulation for 4 weeks of treatment.
METHODS: Patients aged ≥18 years with mild–severe psoriasis were enrolled into three Phase II/III studies (nCT01536886, nCT01536938, nCT01866163); each study evaluated Cal/BD aerosol foam versus different comparators. Endpoints included: proportion of patients clear/almost clear with ≥2-step improvement in physician's global assessment of disease severity (‘treatment success’); modified (excluding head) psoriasis area and severity index (mPASI); proportion of patients with ≥75% reduction in mPASI (PASI75); change in itch (according to visual analog scale [VAS]).
RESULTS: 1104 patients were included in the pooled analysis: Cal/BD aerosol foam (n=564), Cal/BD ointment (n=135), BD aerosol foam (n=101), Cal aerosol foam (n=101), aerosol foam vehicle (n=152), ointment vehicle (n=51). At week 4, 51% of Cal/BD aerosol foam patients achieved treatment success, a higher proportion than in all other groups (Cal/BD ointment, 43%; BD aerosol foam, 31%; Cal aerosol foam, 15%; aerosol foam vehicle, 5%; ointment vehicle, 8%). Greater percentage mean decrease in mPASI with Cal/BD aerosol foam was noted versus other treatments at week 4 (72% vs 63%, 53%, 43%, 32%, and 33%, respectively); week 4 PASI75 rate was also greater (51% vs 41%, 34%, 18%, 7%, and 10%, respectively). Cal/BD aerosol foam was efficacious irrespective of baseline disease severity and on all body areas assessed (arms, legs, trunk). Cal/BD aerosol foam alleviated itch as early as week 1 (change in itch VAS: –30 mm), maintained to week 4 (change in itch VAS: –41 mm).
CONCLUSIONS: Cal/BD aerosol foam was significantly more effective than Cal/BD ointment and the individual active ingredients for treating psoriasis vulgaris, resulting in greater and faster reduction in disease severity and rapid, effective relief of itch.

J Drugs Dermatol. 2016;15(8):951-957.

BACKGROUND/OBJECTIVE: Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis.
METHODS: All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician’s global assessment and the body surface area.
RESULTS: 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (≥ 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort (P=0.004) while biologic prescription rates were significantly lower (P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events (P=0.322 for biologics; P=0.581 for conventional systemics) or infection (P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment (P=0.033).
CONCLUSIONS: This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly safe and effective in the elderly and nonelderly cohorts. Within the elderly population, biologics may be a safer option than conventional systemic agents.

J Drugs Dermatol. 2015;14(8):846-852.

Background: Patients with psoriasis who are treated with systemic and biologic therapies may have an increased risk of infections, including hepatitis B virus (HBV). Cytokines that modulate CD4+ T cell subsets, including interleukin (IL)-12 and IL-23, have been suggested to play a role in the pathogenesis of HBV infection.
Objective: To report the first known cases of acute HBV infection in 2 ustekinumab-treated patients with psoriasis from a phase 3 (PHOENIX 1) and a phase 4 (TRANSIT) study.
Results: Both ustekinumab-treated patients generated an immune response toward HBV and experienced typical courses of infection, without progression to chronic HBV infection.
Conclusion: Continued monitoring of liver-related adverse events in clinical trials, registries, and spontaneous reporting from the postmarketing setting will further contribute to understanding the role of ustekinumab in viral hepatitis.

J Drugs Dermatol. 2012;11(12):1498-1501.

INTRODUCTION: In the Comparative Study of Humira vs Methotrexate vs Placebo In Psoriasis Patients (CHAMPION) study, significantly more patients achieved ≥75% improvement in the Psoriasis Area and Severity Index (PASI75) and ≥90% improvement (PASI90) after 16 weeks of treatment with adalimumab (80 mg at week 0, then 40 mg every other week starting at week 1) compared with methotrexate (up to 25 mg/week orally) or placebo. In this exploratory analysis, the efficacy of adalimumab was evaluated in a subset of the CHAMPION patient population stratified by baseline body mass index (BMI).
METHODS: PASI responses and Dermatology Life Quality Index (DLQI) scores through 16 weeks of treatment were examined by baseline BMI category (<25 kg/m² [normal], 25 to <30 kg/m² [overweight], and ≥30 kg/m² [obese]) in patients with psoriasis with a baseline PASI total score ≥12. Treatment differences between the adalimumab and the methotrexate or placebo groups were compared using Fisher’s exact test for PASI responses and 1-way analysis of variance for DLQI scores.
RESULTS: In all BMI categories, adalimumab treatment led to significantly greater rates of PASI75/90 responses at weeks 12 and 16 compared with methotrexate or placebo (P<0.05 for all). In normal weight, overweight, and obese patients at week 16, the respective PASI75 response rates were 85.0%, 85.7%, and 61.3% with adalimumab; 43.3%, 29.3%, and 26.1% with methotrexate; and 28.6%, 16.7%, and 0% with placebo. PASI90 response rates were 70.0%, 53.6%, and 35.5% with adalimumab; 26.7%, 7.3%, and 8.7% with methotrexate; and 9.5%, 16.7%, and 0% with placebo. Across all BMI subgroups, the greatest decreases in DLQI scores from baseline occurred in the adalimumab group.
CONCLUSION: Significantly higher PASI75/90 response rates and more pronounced improvements in DLQI scores at week 16 were identified in patients treated with adalimumab, compared with methotrexate or placebo, regardless of baseline BMI category.

J Drugs Dermatol. 2015;14(8):864-868.

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Background: Infliximab inhibits T-cell activation by binding tumor necrosis factor-? (TNF-?). This medication is widely used in the US for treatment of psoriasis as an off-label indication. The durability of its effect is largely unknown. Objective: To assess the proportion of patients still on infliximab 12 months after initiation of therapy for psoriasis. Methods: Retrospective chart review analysis of 73 patients with psoriasis treated with infliximab for at least 12 months or those who experienced treatment failure in less than 12 months. The point where infusions were deemed to no longer be efficacious was determined by physicians global assessment (PGA). Results: Of 73 patients who started infliximab at least 12 months prior to this chart review, 22 (30.1%) had discontinued treatment secondary to loss of efficacy. Thirty seven patients (50.7%) had no loss of efficacy and continued to receive infusions. Two patients (2.7%) discontinued due to loss of efficacy after greater than 12 months. Of the 22 patients who discontinued treatment due to loss of efficacy, 2 were on concomitant methotrexate (5-7.5 mg/wk) therapy. Of the 37 patients still receiving treatment with no loss of efficacy at 12 months, 3 patients were on concomitant methotrexate therapy. Five patients (6.8%) discontinued secondary to minor adverse events: sinus infection (1), acne (1), fever (1), arthralgia (1), and transient rash (1). Three patients (4.1%) discontinued due to major adverse events: reactivation of tuberculosis (1), breast cancer (1), and gastrointestinal bleeding (1). One patient discontinued infliximab secondary to concerns of possible lymphoma risk (though there were no signs of symptoms of disease on examination), and 3 patients discontinued due to insurance concerns. Conclusion: Infliximab treatment resulted in significant improvement in psoriasis, with 37 out of 73 patients (50.7%) experiencing no loss of efficacy. This longitudinal retrospective chart review demonstrates continued benefit of infliximab infusions in about half of parients after 1 year, though a notable percentag (30.1%) experienced loss of efficacy as determined by physicians global assessement (PGA) and a number of others discontinued due to adverse events or insurance difficulty.

Recently, the down-titration of the anti-tumor necrosis factor (anti-TNF) agents has become common for the patients with a low disease activity, particularly in rheumatology. However, in dermatology, this practice has not been investigated, even if it is already used by several Psoriasis Centres in Italy. We reviewed the charts of patients treated with in iximab at two Italian Referral Psoriasis Centres. Our study considered a total of 32 patients, whose 20 received in iximab at longer intervals (10 weeks) and 12 at the standard intervals (8 weeks). The group who received the treatment every 10 weeks showed a higher percentage (25%) of relapses, while in the second group, only 2 patients had a worsening of psoriasis (17%). However, the P-value was 0.28, which cannot be considered statistically significant. Our results demonstrated that in iximab could be down-titrated without a significant increase risk of relapses.The main advantage of this administration method may be the improving of the patient’s quality of life. So, for patients with a low disease activity, it may be suitable prolonging the dose intervals. Limitations of our study included the retrospective non- interventional nature and the absence of a control group with the same patient characteristics. J Drugs Dermatol. 2016;15(12):1584-1586.

BACKGROUND: Biologics have changed the way we treat moderate to severe psoriasis. Clinical trials for these patients offer the chance for those suffering from psoriasis to volunteer their time for the advancement of science while possibly gaining benefit from the efficacy of these medications.
OBJECTIVE: All clinical trials have an ending by study design. In the past, trials ended abruptly but it is more common now for transitioning to the approved or another biologic to be offered. Sometimes, study subjects leave clinical trials suddenly for reasons of lack of efficacy, safety, withdrawing consent, being lost to follow-up, or personal reasons. Presenting early experience in transitioning is important for clinicians.
METHODS: A retrospective case series of 11 patients who were exposed to brodalumab from clinical trials that ended abruptly and transitioned to secukinumab is presented.
RESULTS: This is an early descriptive experience of transitioning between two IL-17 antagonists.
LIMITATIONS: A small number of patients were available and a short follow up limited the data presented.
CONCLUSION: Transitioning between two IL-17 antagonists is an option for those patients requiring such a change.

J Drugs Dermatol. 2016;15(8):941-943.

INTRODUCTION: An innovative aerosol foam formulation of calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD) designed to improve treatment outcomes.
OBJECTIVE: To compare the efficacy and safety of Cal/BD aerosol foam with aerosol foam vehicle in patients with psoriasis.
DESIGN: Phase III, double-blind, randomized PSO-FAST (Cal/BD foam in PSOriasis vulgaris, a Four-week, vehicle-controlled, efficacy And Safety Trial) study recruited patients with ≥ mild severity psoriasis of the trunk and/or limbs from 27 US outpatient sites (NCT01866163). Patients were randomized (3:1) to Cal/BD foam or vehicle once-daily for 4 weeks. Primary outcome: proportion of patients at week 4 who achieved treatment success according to physician’s global assessment. Secondary outcomes: modified (excluding head) psoriasis area and severity index (mPASI) and patient's assessment of itch (visual analog scale). Safety was monitored by adverse events/calcium homeostasis.
RESULTS: 426 patients enrolled between June and October 2013 (Cal/BD foam, n=323; vehicle, n=103). At week 4, significantly more patients using Cal/BD foam achieved treatment success versus vehicle (53.3 versus 4.8%; OR 30.3, 95% CI 9.7,94.3; P < .001) and mean mPASI score was significantly lower for patients using Cal/BD foam than vehicle (2.0 versus 5.5; adjusted difference –3.3, P <.001). Significantly greater itch relief was observed for patients using Cal/BD foam than vehicle (P = .010 at day 3, P < .001 from day 5). Adverse drug reactions were reported in 10 Cal/BD foam patients (3.1%) and two vehicle patients (1.9%); events occurred in one patient each except application site pain (Cal/BD foam, two patients; vehicle, one patient). There were no clinically significant changes in calcium homeostasis.
CONCLUSIONS: Cal/BD foam was efficacious, achieved rapid itch relief and was well tolerated in patients with body psoriasis. This innovative aerosol foam formulation is expected to become a valuable treatment option.

J Drugs Dermatol. 2015;14(12):1468-1477.

Background: The past several years have seen the approval of five different biologic agents for the treatment of moderate to severe plaque psoriasis in the United States and Canada. Psoriasis has proven to be a difficult disease to treat and treatment failures, even with newer biologic therapies, are not uncommon. The vast majority of clinical data for these medications is derived from treatment of biologic-naïve patients, or patients who have not responded to, or lost response to, or not tolerated systemic therapy for psoriasis. There is currently little data available on therapeutic response of a second biologic therapy after loss of response, or no response, to the first biologic therapy initiated. It has become common clinical practice to switch medications that are structurally distinct but therapeutically similar in order to achieve an improved clinical outcome. Therapeutic interchange now is being applied to the biologic agents used to treat psoriasis.
Objectives: Using a proof of concept study, describe the response of etanercept after adalimumab has failed to produce a satisfactory response in moderate to severe plaque psoriasis.
Methods: A total of 10 biologically naïve patients with moderate to severe psoriasis who were initiated on adalimumab for at least 12 weeks but had a Physician’s Global Assessment (PGA) of mild or worse were transitioned to commercial etanercept 50 mg twice weekly (BIW) for 12 weeks followed by a dose reduction to 50 mg once weekly (OW) for an additional 12 weeks. Ethics approval was obtained and the study registered with ClinicalTrials.gov (NCT00833729). The primary outcome measured was the mean change in Physician’s Global Assessment (PGA) score (range 0-5) from baseline (when the first etanercept injection is given) to 12 weeks of etanercept therapy. The secondary outcomes measures included the mean change in Dermatology Quality of Life Index (DLQI), mean change in body surface area (BSA) covered in psoriasis, Subject’s Global Assessment of disease (SGA), proportion of patients achieving an improvement in PGA score from baseline to 12 weeks and again at 24 weeks and safety.
Results: Overall, there were significant favorable changes in all outcomes measured (PGA, SGA, BSA and DLQI) with respect to etanercept’s efficacy after an inadequate response to at least 12 weeks of adalimumab therapy. There were no significant safety issues noted especially during the transition period from adalimumab to etanercept. ClinicalTrials.gov identifier: NCT00833729.

J Drugs Dermatol. 2011;10(4):396-402.

Background: Available biologic agents for the treatment of psoriasis in China are limited.
Objectives: The LOTUS study is a phase 3, double-blind, placebo-controlled study that evaluated the efficacy and safety of ustekinu-mab in Chinese patients with moderate to severe plaque-type psoriasis.
Patients and Methods: Patients (n=322) were randomized to receive ustekinumab 45 mg or placebo at weeks 0 and 4, with placebo crossover to ustekinumab at week 12; all patients were followed up to week 36. The primary end point was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) at week 12. Other end points at week 12 included the proportion of patients with a Physician's Global Assessment (PGA) score of 0 or 1 and the change in Dermatology Life Quality Index (DLQI) score from baseline.
Results: At week 12, 82.5% of ustekinumab-treated patients achieved PASI 75 responses compared with 11.1% of placebo-treated patients (P<.001). Clinical responses were maintained through week 28, with maximum responses observed at week 24. Significant improvements in PGA and DLQI were observed at week 12 and were generally maintained through week 28. At week 12, adverse events rates were similar between groups (45 mg: 42.5% vs placebo: 38.5%), and serious adverse events were reported in 0.6% of patients in each group. Through week 36, no cases of active tuberculosis, serious infections, malignancies, or major adverse cardiovascular events were reported.
Conclusions: Consistent with results previously reported in global phase 3 studies, ustekinumab was highly effective and generally well tolerated in Chinese patients with moderate to severe psoriasis through 36 weeks.

J Drugs Dermatol. 2013;12(2):166-174.

BACKGROUND: Psoriasis treatments and therapeutic response as they relate to private versus public patient insurance in the United States have not yet been reviewed. Improved understanding could clarify factors challenging optimal psoriasis management and offer insight for dermatologists treating psoriasis within our healthcare system.
METHODS: 258 subjects were included from a database of psoriasis patients seen at Tufts Medical Center (Boston, MA) during 2008-2014. Insurance was classified as primarily private or public (Medicare or MassHealth/Medicaid). Patients required a minimum of two consecutive visits per treatment and at least 8 weeks within one of four treatment categories: biologics, oral systemics/ phototherapy, combined biologics and oral systemics/phototherapy, or topicals only. Primary endpoint was the Simple-Measure for Assessing Psoriasis Activity (S-MAPA) calculated by multiplying Physician Global Assessment by Body Surface Area. S-MAPA<3 constituted absolute clearance. Insurance type was evaluated as a predictor of prescribed treatment categories, maximum S-MAPA
improvement from baseline, and total drugs used per treatment course (“drug-switching”).
RESULTS: 80.2% (n=207) and 19.8% (n=51) had primarily private and public insurance, respectively. 69.6% with private insurance were prescribed biologics versus 66.7% (public insurance) (P=0.689). 54% (private) versus 49% (public) achieved clearance (P=0.514). However, S-MAPA decreased 78.35% from baseline in those with private insurance compared to 61.48% (public) (P=0.036). On average, privately insured patients used at least twice as many same-category treatments, most commonly biologics, than publicly insured individuals (P=0.003). Drug-switching was significantly associated with clearance (P=0.024). Multivariate analysis demonstrated no significant differences in prescribed treatment categories, drug efficacy, clearance, S-MAPA, or drugswitching with respect to patient age.
CONCLUSIONS: Treatment categories were comparably prescribed between insurance subgroups. However, privately insured patients achieved significantly greater degrees of clearance and switched between more medications within biologic and systemic categories, potentially explaining their overall improved therapeutic response. Further studies including cost-analysis could clarify any difference in the effectiveness of prescribed therapy for these two patient populations.

J Drugs Dermatol. 2015;14(2):119-125.

Background: Etanercept has been used to treat chronic plaque psoriasis. Previously reported data demonstrated that some patients experienced secondary failure and frequently rotational-switch therapy is used. The re-treatment with etanercept as part of the rotational therapy could be considered as another safe and efficient therapeutic approach.
Objective: To evaluate the efficacy of the re-treatment with etanercept in patients with a history of etanercept use with good response and secondary loss of efficacy.
Methods: This is an open label prospective study involving 20 patients with moderate to severe plaque psoriasis, who had been initially treated with etanercept and were re-treated after a variable interval with 50 mg BIW for 12 weeks.
Results: At week 12 of etanercept re-treatment, 13 of 20 patients (65%) achieved a PGA score of 2 or less and 40% (8 of 20), achieved a PGA score of 0 to 1. Etanercept was well tolerated and no serious adverse events were reported.
Limitations: Our study involved a small number of patients. Failure of etanercept was establish by patient's history. However we were able to correlate such failure from our medical records in 17 patients.
Conclusions: Re-treatment with etanercept, after secondary loss of efficacy should be considered in patients with psoriasis if satisfactory therapy cannot be achieved with other therapeutic regimens.

J Drugs Dermatol. 2012;11(8):950-954.

One of the hurdles to effectively managing plaque psoriasis is lack of adherence to prescribed treatments. Up to 40% of subjects report they do not adhere to their medication for a variety of reasons. Earlier response to treatment may be a motivator for subjects to better adhere to treatment. Clobetasol propionate 0.05% spray (CPS) is a highly potent topical corticosteroid indicated for the treatment of moderate to severe plaque psoriasis that has efficacy as early as 1 week after initiating therapy. Using data from the 2 CPS pivotal trials, a post hoc analysis was performed to determine the relationship between week 1 improvements and week 4 treatment success (defined as a score of 0 [clear] or 1 [almost clear] in overall disease severity [ODS]). Improvements in week 1 ODS and pruritus were predictive of week 4 treatment success. Subjects who had ODS or pruritus scores of moderate or better at week 1 tended to be treatment successes at week 4 whereas no relationship between week 1 scores and week 4 treatment success was observed for those treated with vehicle spray. The results of this post hoc analysis indicate that early improvement correlates to treatment success.

J Drugs Dermatol. 2013;12(12):1456-1460.

BACKGROUND: Nails, one of the most visible sites of body, are frequently involved in psoriasis and accepted as the most difficult site for topical treatment because of their anatomical structure. Healing of the psoriatic nails usually occurs when systemic therapy is initiated to treat severe skin psoriasis or joint involvement, but sometimes systemic therapy is essential for severe nail psoriasis, although Psoriasis Area and Severity Index (PASI) score is low or none of the joints are affected. In this case, knowing which systemic agent is most potent on nail findings is important.
AIM: We aimed to evaluate the effect of systemic antipsoriatic agents on nail findings.
METHODS: Eighty-seven psoriatis patients with fingernail involvement who required systemic treatment but had not used any systemic treatment in the previous 12 weeks were included in this study. Different systemic treatment agents were given to patients, considering factors such as age, sex, and joint involvement, but not nail involvement. The control group was recruited from psoriatis patients with nail involvement who were not receiving any systemic treatment. Baseline and week 16 Nail Psoriasis Severity Index (NAPSI) and PASI were detected in all groups. At the end of the study, effects of the agents on both PASI and NAPSI were compared statistically.
RESULTS: Patients were divided into 5 groups to receive either: 1) methotrexate, 2) narrow-band ultraviolet B phototherapy, 3) biological agents, 4) acitretin, or 5) no treatment (control group). None of the conventional treatment agents caused any significant difference on NAPSI at the end of week 16 compared with control group, although PASI decreased significantly. Rate of NAPSI changes were more prominent in the biological treatment group, and a statistically significant difference was detected when compared with the control group.

J Drugs Dermatol. 2013;12(9):1039-1043.

No abstract details for the moment.

BACKGROUND: Secukinumab, a human monoclonal antibody that selectively targets interleukin-17A, is highly efficacious in the treatment of moderate-to-severe psoriasis, starting at early time points, with a sustained effect and a favorable safety profile. METHODS: Patients with moderate-to-severe plaque psoriasis were randomized to secukinumab 300 mg, secukinumab 150 mg, or placebo self-administered by prefilled syringe at baseline, weeks 1, 2, and 3, and then every four weeks from week 4 to 48. Efficacy responses (≥ 75/90/100% improvement in Psoriasis Area and Severity Index [PASI 75/90/100] and clear/almost clear skin by Investigator’s Global Assessment 2011 modified version [IGA mod 2011 0/1]) were measured to week 52. Patient-reported usability of the prefilled syringe was evaluated by the Self-Injection Assessment Questionnaire to week 48. RESULTS: The efficacy of secukinumab increased to week 16 and was maintained to week 52. With secukinumab 300 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 83.5%/68.0%/47.5% and 71.5% of patients when analyzed by multiple imputation, respectively, and by 75.9%/62.1%/43.1% and 63.8% of patients when analyzed by nonresponder imputation, respectively. With secukinumab 150 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 63.5%/50.3%/31.1% and 43.6% of patients when analyzed by multiple imputation, respectively, and by 61.0%/49.2%/30.5% and 42.4% of patients when analyzed by nonresponder imputation, respectively. Self-reported acceptability of the prefilled syringe was high throughout the study. The incidence of adverse events (AE) was well balanced between groups, with AEs reported in 74.4% of patients receiving secukinumab 300 mg and 77.3% of patients receiving secukinumab 150 mg. Nasopharyngitis was the most common AE across both secukinumab groups. CONCLUSION: Self-administration of secukinumab by prefilled syringe was associated with robust and sustained efficacy and a favorable safety profile up to week 52.

J Drugs Dermatol. 2016;15(10):1226-1234.

BACKGROUND: Adalimumab is an anti-TNF biologic drug that is efficacious in the treatment of psoriasis. However, the effect of adalimumab on genome-wide gene expression changes in skin and peripheral blood is not well characterized.
METHODS: Thirty adult subjects with > 10% body surface area of chronic plaque psoriasis were recruited for the study. Lesional skin and peripheral blood mononuclear cell samples prior to and one month following treatment with adalimumab were collected. The skin samples were analyzed using genome-wide RNAseq, and the blood samples were analyzed using genome-wide Affymetrix microarrays. Data preprocessing and analysis were conducted using the EdgeR and Affy packages in R/Bioconductor.
RESULTS: In the skin, paired analysis before and after treatment revealed changes in pathways important to epidermal development and keratinocyte differentiation. Such important genes as keratin 6A and 6B, tubulin B6, desmocollin, and desmoglein 3 were among the top differentially expressed genes. In peripheral blood, pathways involved in hematopoetic cell lineage and immune response were found to be differentially expressed, including genes such as the Fc receptor-like A and 5, as well as immunoglobulin heavy chains. Using a principal components approach, we show that expression of genes in post-treatment skin more closely resembles that of healthy controls.
CONCLUSION: Treatment of psoriasis with adalimumab appears to be associated with modulation of keratinocyte and epidermal proliferation in the skin and with immunologic changes in the blood. We discuss the ramifications of these findings for the treatment for psoriasis.

J Drugs Dermatol. 2016;15(8):988-994.

Ustekinumab is effective in the treatment of a variety of autoimmune conditions including psoriasis. As a relatively new therapeutic agent, its long-term effects are still under investigation. Short-term studies, however, have revealed ustekinumab to be generally well tolerated and safe. This article provides a comprehensive review of the pharmacokinetics of ustekinumab, its safety profile, adverse effects, and use in pregnancy. The effect of diabetes and prior immunosuppressant therapy is also addressed.

J Drugs Dermatol. 2012;11(8):907-910.

Clobetasol propionate 0.05% spray (CPS) is a topical, super-high-potent corticosteroid indicated for the treatment of moderate to severe plaque psoriasis. Two pivotal trials of CPS investigated the efficacy and safety of treatment in subjects with moderate to severe plaque psoriasis. Overall disease severity (ODS), erythema, plaque elevation, scaling, and pruritus were assessed on a 5-point scale of 0 (clear) to 4 (severe/very severe). Overall disease severity treatment success was defined as achieving a score of ≤2 at week 2 and a score of ≤1 at week 4. Treatment success for all other parameters was defined as achieving a score of ≤1 at all time points. Based on Cochran-Mantel-Haenszel analysis, treatment success was achieved in the CPS group in both studies compared with vehicle after 2 weeks, but not after 1 week. Only subjects who achieved treatment success were considered for analysis. Thus, subjects who did not meet the criteria for treatment success were not examined for improvement. A post hoc analysis was conducted using all the data and the median as the measure of central tendency. It was shown that ODS, erythema, plaque elevation, scaling, and pruritus improved by 1 grade from baseline at week 1 in subjects given CPS. The data presented here suggest CPS is effective in improving the signs and symptoms of plaque psoriasis 1 week after initiating treatment.

J Drugs Dermatol. 2012;11(12):1455-1459.

Background: Psoriasis is a common skin disease in Caucasians but less common in African-Americans.
Aims: Our aim is to evaluate caregiver opinions regarding the clinical presentations and treatment of psoriasis in African-Americans compared to Caucasians.
Patients/Methods: A survey was sent to 29 dermatologists who are opinion leaders in the field of psoriasis. The survey included a number of questions regarding the characteristics of the patients seen in their practice.
Results: A total of 29 surveys were completed and returned. All of the dermatologists use the extent of disease as a criterion to determine the severity of the disease. Other criteria include scale, thickness, erythema, associated general symptoms, and dyspigmentation. About 66% of the respondents reported the different manifestations of disease, such as more dyspigmentation, thicker plaques, and less erythema in African-Americans. The most common first-line treatments for mild to moderate disease were highpotency topical steroids (68%) followed by topical vitamin D analogues (41%). For moderate to severe disease, the most commonly used first-line treatments were high-potency topical steroids (54%) and phototherapy (46%).
Conclusions: The clinical manifestations of psoriasis in African-Americans are not exactly the same as in Caucasians. Physicians should be aware of the difference in clinical manifestations in African-Americans. Further research and large-scale studies are necessary to elucidate the differences in the clinical presentation, natural course of the disease, and the criteria used for the evaluation of severity among ethnic groups.

J Drugs Dermatol. 2012;11(4):478-482.

Background: Psoriasis is a hyperproliferative and inflammatory skin disorder that affects roughly 2 percent of the worldwide population. Clobetasol propionate is the most common corticosteroid used to treat moderate-to-severe psoriasis but the potential for side effects limits its long-term use. Topical vitamin D, which is used to treat mild-to-moderate psoriasis, has been shown to be safe when used daily for up to 52 weeks. To date, very few studies exist evaluating the use of clobetasol propionate in a regimen with calcitriol to manage moderate-to-severe disease over time. Objectives: To evaluate the efficacy and assess safety of a regimen of sequential topical treatments with clobetasol propionate 0.05% spray for up to four weeks followed by calcitriol 3 μg/g ointment for eight weeks in the management of moderate-to-severe plaque psoriasis. Methods: This was a multi-center, open-label study in subjects aged 18–80 years with moderate-to-severe plaque psoriasis at baseline. Subjects applied clobetasol propionate 0.05% spray twice daily for up to four weeks. At the end of four weeks, if the subject’s overall disease severity (ODS) was assessed as clear, almost clear, mild or moderate, subjects started treatment with calcitriol 3 μg/g ointment twice daily. Twice-daily treatment with calcitriol 3 μg/g ointment continued for eight weeks (until week 12) or unless the subject’s ODS was assessed as severe or returned to the baseline score, at which time it was discontinued. Subjects were evaluated at baseline and at weeks 2, 4, 8 and 12. Results: Of the 305 subjects enrolled, 170 subjects completed the full 12-week study with no major protocol deviations and comprised the per-protocol (PP) study population. Treatment success, defined as at least one grade improvement in ODS at week 12 compared to baseline, was achieved in 84.1 percent of subjects. The percent body surface area affected (% BSA) decreased from 7.1 percent at baseline to 3.9 percent at week 12 (P<0.001). The sequential treatment regimen was well tolerated with no unexpected adverse events. Most reported adverse events and cutaneous irritations were mild in severity. Conclusions: The results of this study indicate that the 12-week regimen of clobetasol propionate 0.05% spray treatment for four weeks immediately followed by an eight-week treatment phase with calcitriol 3 μg/g ointment is efficacious and safe for the management of moderate-to-severe plaque psoriasis. J Drugs Dermatol. 2011;10(2):158-164.

Introduction: Acitretin is a systemic retinoid drug used in the treatment of severe psoriasis. It has also been used for a spectrum of other difficult-to-treat dermatoses, including hyperkeratotic and inflammatory dermatoses and non-melanoma skin cancers. Here we review the available data regarding both FDA-approved and off-label uses of acitretin, clinically relevant adverse events, precautions and monitoring.
Methods: A PubMed literature search was conducted utilizing the search term "acitretin," which yielded 714 hits. Results were further limited to English language clinical trials in human subjects. Of 78 articles evaluated for relevance, 60 were included for review.
Results: Acitretin is effective as monotherapy and in multidrug therapeutic regimens for the treatment of psoriasis and other hyperkeratotic and inflammatory disorders, as well as for malignancy chemoprevention. Its use is limited by its teratogenic potential and other adverse effects, including mucocutaneous effects and hepatotoxicity. Potential adverse effects may be reduced or avoided by using lower doses of acitretin or in combination with other therapies.
Limitations: The reviewed studies include many small trials and case reports of the use of acitretin for psoriasis. Studies of acitretin therapy for the treatment of other cutaneous disorders are limited.
Conclusion: Acitretin is a beneficial treatment for psoriasis, and should be considered when not contraindicated. Particularly when used in combination with ultraviolet (UV) phototherapy, is a safe and cost effective therapeutic strategy.

J Drugs Dermatol.2011;10(7):772-782.

BACKGROUND: Although biologic therapies have been shown to be more effective than traditional systemic therapies in clinical trials for the treatment of psoriasis, the drug survival time and reasons for discontinuation of biologics in clinical practice have not been compared with those of conventional systemic therapies.
DESIGN: Retrospective, cross-sectional.
METHODS: All patient visits coded for psoriasis (ICD-0 696.1) in the clinical practice of 2 dermatologists from January 1 2008 through January 4 2012 were included in this retrospective data analysis. The practice is a comprehensive psoriasis care center in the northeastern United States serving a metropolitan population of over 4 million people. Patients were divided by treatment type: biologic or traditional systemic. Treatment failure was defined as discontinuation of treatment course for any reason. Patient time to failure for each therapy was calculated, as were previous treatments and reasons for treatment discontinuation.
RESULTS: One hundred and fifty-nine patients who underwent 284 courses of treatment were studied. Forty-eight percent of biologics failed in an average of 242 days, compared with 75% of traditional systemics (P<.0001), which failed in an average of 143 days (P<.0001). Infliximab had the longest survival time (292 days), and ustekinumab had the smallest failure rate (39%). Reasons for discontinuation differed significantly between biologics and systemics, with biologics being discontinued more often due to loss of efficacy (P=.0014), and systemics failing significantly more frequently due to adverse events (P<.001). Adverse events were observed most frequently with methotrexate and infliximab, while golimumab had the highest rates of both loss and lack of efficacy.
CONCLUSION: Biologics had longer survival times and lower failure rates than traditional systemics in the treatment of psoriasis. Biologics were more likely to be discontinued due to loss of efficacy, and systemics were more likely to fail due to adverse events.

J Drugs Dermatol. 2014;13(7):848-853.

Two Phase 3, double-blind, randomized, vehicle-controlled parallel studies evaluated the efficacy and safety of desoximetasone spray 0.25%, a super-potent topical corticosteroid, twice daily vs vehicle spray twice daily for 28 days in adult patients with moderate to severe plaque psoriasis. At baseline and throughout the study, the severity of disease for the psoriatic lesions was assessed using the Physician Global Assessment (PGA) score and a target lesion was assessed using the Total Lesion Severity Score (TLSS). A designated psoriatic plaque lesion was selected as the target lesion upon enrollment and evaluated throughout the study to determine the TLSS. To qualify for study entry, the subject needed to exhibit a PGA score of 3 (moderate) or 4 (severe) for overall disease severity, and a target lesion with an area of at least 5 cm2 that achieved a combined score TLSS of >=7, with a plaque elevation score of >=3 (at least moderate). The mean % BSA affected by psoriasis ranged from 13%-17% at baseline.

In both Phase 3 studies, a statistically significantly greater percentage of subjects in the desoximetasone spray 0.25% compared to vehicle group achieved both Clinical Success and Treatment Success at Day 28. These results, which were the primary efficacy variables, demonstrated superior efficacy in the active study group for both overall improvement of plaque psoriasis (by PGA) and in the individual psoriasis lesion (by TLSS) designated at baseline as the most severely involved plaque (target lesion). Assessment of secondary efficacy variables in both Phase 3 studies showed that subjects receiving desoximetasone Spray 0.25% twice daily exhibited statistically significantly mean changes from Baseline to Day 28 in PGA, TLSS, and % BSA affected when compared to subjects receiving vehicle spray twice daily.

Tolerability and safety were assessed at all study visits. No statistically significant differences were observed between study arms and no major safety signals related to AEs were noted. No stinging and burning were reported with the spray formulation. This Class I topical corticosteroid has shown to be safe and efficacious in moderate to severe plaque psoriasis.

J Drugs Dermatol. 2013;12(12):1404-1410.

Of the topical preparations available, the ultra-high potency corticosteroids have an important role in treating psoriasis. However, the use of these agents in many other conditions and patient populations may not be appropriate. This study examines the prescribing patterns of Class I topical corticosteroids in patients with skin disease by analyzing data from the National Ambulatory Medical Care Survey (1990-2000). Of the nearly 718 million visits for skin disease, Class I topical corticosteroids were prescribed in nearly 3% of all skin disease-related visits, with prescription rates being highest in psoriasis (22%). The study found greater prescription rates of Class I topical steroids by dermatologists compared to non-dermatologists [Odds Ratio (OR) = 4.39 (95% CI: 2.15, 8.99)]. However, there were also a large number of questionable prescriptions for other conditions, which could be construed as misuse of these medications. Despite limitations and the potential dubious use seen here, Class I topical corticosteroid use is relatively commonplace. Education efforts and novel preparations of Class I agents will help to ensure the best possible care for patients suffering from significant skin diseases like psoriasis.

Dermatological research continues to move toward the goal of developing an effective psoriasis treatment that would rapidly clear lesions and provide long-term freedom from visible signs and symptoms. Currently, topical corticosteroids remain a pivotal treatment due to their effective anti-inflammatory properties; however, potential adverse effects associated with chronic application limit long-term continuous therapy. Vitamin D analogues provide another mechanism of action, reducing lesions through effects on both keratinocytes and on the cytokine environment. A topical combination of corticosteroid and vitamin D derivative appears to provide a balanced approach to psoriasis treatment. The development of clobetasol propionate foam 0.05% (clobetasol propionate foam/Olux) offers a convenient topical corticosteroid that can be used concomitantly, that is, immediately followed by application of calcipotriene ointment 0.005% (Dovonex). This regimen has been shown to offer an increased short-term efficacy compared with either agent alone. Continued application of calcipotriene ointment on weekdays supplemented by long-term clobetasol propionate foam pulse therapy on weekends appears to provide an enhanced maintenance of remission compared with calcipotriene monotherapy.

Tumor necrosis factor (TNF)-α inhibitors are currently the gold standard for treating moderate to severe plaque psoriasis and other immune-mediated diseases. The presence of previously existing demyelinating disease is amongst the contraindications to their use. However, controversy surrounds the use of TNF-α inhibitors in patients who are more predisposed to developing multiple sclerosis (MS), specifically first-degree relatives of MS patients. In fact, the major guidelines committees’ recommendations on this issue by the American Academy of Dermatology, the British Association of Dermatologists, and the European S3-Guidelines are not consistent. The data we present suggest that the number needed to treat is at least an order of magnitude smaller than the number needed to harm across all comparisons of anti-TNF-α agents and first-degree relative relationships. Based on these data, physicians could weigh the treatment options available and work closely with neurological colleagues when prescribing anti-TNF-α therapy in this patient population rather than practicing absolute prohibition of anti-TNF-α agents in patients who have a first-degree relative with MS.

J Drugs Dermatol. 2015;14(8):876-878

The two-compound ointment (Taclonex®/Daivobet®/Dovobet® ointment) combining calcipotriene 50 μg/g and betamethasone 0.5 mg/g (as dipropionate) is very effective in the treatment of psoriasis vulgaris. There is a possibility that hypothalamo-pituitaryaxis (HPA) suppression may occur if the potent corticosteroid component is absorbed to a sufficient extent. The effect of the two-compound ointment on HPA axis function was assessed in two studies. Study 1 was a four-week, double-blind study which compared the effects of the two-compound ointment with betamethasone 0.5 mg/g (as dipropionate; Diprosone®) ointment in 24 patients with extensive psoriasis (involving 15–30% of the body surface area). No patients receiving the two-compound ointment had HPA axis suppression. Study 2 assessed HPA axis function after four and 52 weeks in a subset of patients (n=19) participating in a long-term safety study. Patients were treated with the two-compound ointment for the first four weeks followed by 48 weeks of treatment as needed with either 1) two-compound ointment; 2) two-compound ointment alternating with calcipotriene four-weekly or 3) calcipotriene. No patients using the two-compound ointment for all 52 weeks or alternating four-weekly with calcipotriene had HPA axis suppression.

Cyclosporine is an immunosuppressive drug that acts selectively on T-cells by inhibiting calcineurin phosphorylase. It has been used in dermatology since its approval for US Food and Drug Administration in 1997 for the use in psoriasis. While indicated only for the treatment of moderate to severe psoriasis, cyclosporine has also been used as an off-label drug for the treatment of various inflammatory skin conditions, including atopic dermatitis, blistering disorders, and connective tissue diseases. In this article, we review the use of cyclosporine in dermatology.

J Drugs Dermatol. 2012;11(8):979-987.

Psoriasis Is a Chronic Disease: Long Term Efficacy and Safety of New Biologics Is Important

Acitretin, the only oral retinoid indicated for the treatment of psoriasis, has shown activity when used in combination, rotational, and sequential therapy regimens with other therapies. When used with phototherapy, significantly greater activity has been observed at lower doses than with either approach as monotherapy. While initial anecdotal evidence is promising, clinical trials are needed to evaluate whether sequential or rotational use of biologic agents with acitretin may yield improved efficacy and an acceptable safety profile with decreased risk of immunosuppression. Acitretin and other retinoids also work as chemopreventative agents in psoriasis patients with extensive exposure to psoralen ultraviolet A (PUVA) and in solid-organ transplant patients where a number of studies have reported decreased numbers of squamous cell cancers when treated with acitretin.

BACKGROUND: Treatment with tumor necrosis factor (TNF)-α antagonists is effective in patients with moderate-to-severe plaque psoriasis, including those with impaired health-related quality of life (HRQoL).
METHODS: PSUNRISE is a multicenter, open-label, prospective study evaluating the efficacy and safety of switching from etanercept to infliximab in psoriasis patients with an inadequate response to etanercept. Patients received intravenous infusions of infliximab 5 mg/ kg at weeks 0, 2, 6, 14, and 22. HRQoL was assessed using the Dermatology Life Quality Index (DLQI), the 36-item Short-Form Health Survey (SF-36), and the EuroQoL (EQ-5D) index and EQ-5D visual analog scale (VAS; 0-100 cm) among patients receiving at least one infliximab infusion. Subgroup analyses (t- test) were performed to compare mean DLQI improvement between patients who achieved and did not achieve clinical response (Physician’s Global Assessment [PGA] 0/1 and at least a 75% improvement in the Psoriasis Area and Severity Index [PASI 75]) at weeks 10 and 26.
RESULTS: A total of 215 patients received at least one infliximab infusion. A DLQI score of 0 or 1 (no negative effect on HRQoL) was achieved by 3.7%, 44.2%, and 41.4% of patients at weeks 0, 10 and 26, respectively. Mean changes in SF-36 Physical Component Summary scores were 1.8 (week 10) and 2.4 (week 26); corresponding changes in Mental Component Summary scores were 4.5 and 5.0. The mean change in EQ-5D index score was 0.08 at week 10 and 0.09 at week 26; respective mean changes in EQ-5D VAS score were 7.73 and 9.49. Mean improvements in DLQI were significantly higher for patients achieving versus those not achieving PGA 0/1 (P=0.0193 [week 10] and P=0.0010 [week 26]) and PASI 75 response (P<0.0001 [week 10]; P=0.0012 [week 26]).
CONCLUSION: Psoriasis patients with prior inadequate response to etanercept demonstrated sustained improvements in HRQoL after switching to infliximab, and HRQoL improvements were associated with clinical responses.

J Drugs Dermatol. 2013;12(8):874-880.

Background: Long-term observational studies can better characterize the impact of systemic agents on psoriasis.
Objective: To describe the on-going Psoriasis Longitudinal Assessment and Registry (PSOLAR) study.
Methods: PSOLAR is a large, international, long-term, prospective, disease-based registry enrolling patients with psoriasis who are receiving, or are candidates for, treatment with systemic therapies. The registry fulfills postmarketing regulatory commitments and charges a global Steering Committee to manage epidemiological research on psoriasis and its therapies. Key demographics, disease characteristics, and medication history are collected at enrollment. Adverse events and efficacy data are collected longitudinally.
Results: The August 2011 annual database extract includes 9,495 patients enrolled at 266 global centers. At entry, mean percent of body surface area affected by psoriasis was 12.3% (peak, 29.5%). Approximately 80% of patients were overweight/obese, more than one-third had cardiovascular disease (38.8%) or psoriatic arthritis as captured by the treatment center (37.1%), and over half had received one or two biologic agents (58.8%) or phototherapy (54.8%). Mean duration of participation is 1.3 years, and annual withdrawal rates are less than 6.5%. Of 9,495 patients, 7,476 have been exposed to at least one biologic agent. Serious infections, malignancies, all-cause mortality, and major adverse cardiovascular events (ie, myocardial infarction, stroke, cardiovascular death) occurred at rates of 1.40, 0.61, 0.37, and 0.36 per 100 patient-years of follow-up, respectively.
Limitations: PSOLAR may be subject to limitations common to observational studies (eg, participation bias and potential confounders).
Conclusion: PSOLAR is a disease-based registry designed to assess therapeutic risk and benefit in the general psoriasis population.

J Drugs Dermatol. 2012;11(10):1210-1217.

IMPORTANCE: While psoriasis (Ps) is mainly characterized as an adult disease, it can also develop during childhood. However, prevalence estimates of pediatric psoriasis in the United States (US) are lacking. OBJECTIVE: To assess the 2015 annual prevalence of Ps and moderate-to-severe Ps in pediatric individuals in the US. DESIGN: This is a retrospective study based on a large administrative insurance claims database in the US. SETTING: Data were extracted from the Truven Health Analytics MarketScan® Commercial Claims and Encounters database, which covers over 60 million individuals with employer-provided health insurance across the US. PARTICIPANTS: Over 4.3 million of individuals continuously enrolled in their healthcare plan in 2015 and under 18 years of age were included in the study. Intervention(s) for Clinical Trials or Exposure(s) for Observational Studies: Not applicable. Main Outcome(s) and Measure(s): Ps was defined based on medical claims with a diagnosis of Ps (ICD-9-CM: 696.1); moderate-to-severe Ps was defined based on medical or pharmacy claims for a systemic treatment (biologic, conventional systemic, or phototherapy) for Ps. Overall and age- and gender-stratified prevalence was estimated for both Ps and moderate-to-severe Ps. RESULTS: The prevalence of Ps was estimated at 128 cases per 100,000 individuals (95% CI: 124-131), that of moderate-to-severe Ps at 16 cases per 100,000 individuals (95% CI: 15-17) in 2015. For both Ps and moderate-to-severe Ps, prevalence estimates were numerically higher in females than in males (146 per 100,000 vs. 110 per 100,000 and 17 per 100,000 vs. 15 per 100,000) and increased with age, ranging from 30 per 100,000 in the 0-3 year old group to 205 per 100,000 in the 12-17 year old group. CONCLUSION AND RELEVANCE: This study provides robust estimates of the prevalence of pediatric Ps that can inform decisions pertaining to the management of pediatric patients with Ps. J Drugs Dermatol. 2018;17(2):187-194.

BACKGROUND: Early follow-up visits improve patient adherence, but the actual scheduling behavior of physicians is not known.
PURPOSE: To characterize the timing of first follow-up visits in US dermatologic practice.
Methods: Patients with a diagnosis of psoriasis, acne, or atopic dermatitis were identified in the 2003-2007 MarketScan Medicaid database. Factors affecting the length of time before first follow-up were assessed using a Cox proportional hazards model.
RESULTS: Mean length of time to the first follow-up visit was 153 days for adults and 142 days for children with psoriasis; 151 days for adults and 218 days for children with acne; and 161 days for adults and 209 days for children with atopic dermatitis. Black and those other than white patients were less likely than whites to receive early follow-up in psoriasis and acne, but more likely in atopic dermatitis. Dermatologists were more likely to schedule early follow-up visits than nondermatologists.
LIMITATIONS: The database includes only Medicaid patients. The rate of non-attendance at scheduled visits could not be determined.
CONCLUSIONS: Most physicians are missing the opportunity to maximize patient adherence by scheduling early follow-up visits. Contact by email or phone may be beneficial for physicians who cannot schedule early follow-up.

J Drugs Dermatol. 2014;13(7):833-836.

INTRODUCTION: We evaluated post hoc the relationship between Humira^® (adalimumab) therapy and high-sensitivity C-reactive protein (hs-CRP) levels in patients with moderate-to-severe hand and/or foot psoriasis from the 16-week placebo-controlled period of REACH.
METHODS: REACH was a phase 4, multicenter, randomized, double-blind trial, evaluating adalimumab treatment for patients with psoriasis of the hands and/or feet. Adults were randomized 2:1 to adalimumab 40 mg every other week (following 80 mg at week 0) or matching placebo from weeks 1 to 16, followed by a 12-week, open-label extension. In this post hoc analysis, changes in hs-CRP were reported as observed from baseline to week 16.
RESULTS: Of the 72 patients (23 placebo, 49 adalimumab) who participated in REACH, 63 (19 placebo, 44 adalimumab) with hs-CRP measurements at baseline and at week 16 were included in this analysis. Baseline median hs-CRP values were 1.6 mg/L (placebo) and 2.2 mg/L (adalimumab), and were 3 times higher for patients with, as compared with those without, psoriatic arthritis (5.45 vs 1.8 mg/L). At week 16, the adalimumab group showed greater improvements (median reduction) from baseline than the placebo group in hs-CRP overall (−0.55 vs +0.10 mg/L), regardless of achievement of PGA of the hands and/or feet (hfPGA) 0 or 1 at week 16 (−0.80 vs 0 mg/L for patients who achieved hfPGA 0/1; −0.40 vs +0.30 mg/L, patients who did not achieve hfPGA 0/1), baseline psoriatic arthritis history (−2.35 mg/L with history [adalimumab group; no history for placebo group]; −0.40 vs +0.10 mg/L without history), and body mass index (BMI) category (defined by median BMI) (−0.80 vs +0.20 mg/L for BMI <30.28 kg/m²; −0.40 vs 0 mg/L for BMI ≥30.28 kg/m²).
CONCLUSION: Treatment with adalimumab 40 mg every other week resulted in greater overall reductions in hs-CRP levels among patients in this post hoc analysis, compared with placebo at 16 weeks regardless of baseline characteristics.

ClinicalTrials.gov Registry for REACH: NCT00735787

J Drugs Dermatol. 2016;15(5):562-566.

BACKGROUND: Newer psoriasis treatments can achieve greater levels of effcacy than older systemic therapies; however, current pso-riasis costs are substantial. We sought to estimate costs per additional responder associated with ixekizumab and etanercept, versus placebo, using effcacy data from phase 3 clinical trials (UNCOVER-2 and UNCOVER-3).

METHODS: In UNCOVER-2/UNCOVER-3, patients received subcutaneous placebo, etanercept 50 mg twice weekly (BIW), or ixekizumab one 80 mg injection every 2 weeks (Q2W) after a 160-mg starting dose. Twelve-week induction-phase Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 response rates for ixekizumab, etanercept, and placebo were obtained from pooled data from the overall and United States (US) subgroup intention-to-treat (ITT) populations, and used to calculate numbers needed to treat (NNTs) to achieve one additional PASI 75, PASI 90, or PASI 100 response for ixekizumab Q2W and etanercept BIW versus placebo. Twelve-week drug costs per patient were calculated based on the UNCOVER-2/UNCOVER-3 dosing schedule and wholesale acquisition costs. Mean costs per additional responder for PASI 75, PASI 90, and PASI 100 for each treatment versus placebo were calculated for pooled UN-COVER-2/UNCOVER-3 overall and US subgroup ITT populations.

RESULTS: Pooled overall ITT population: costs per additional PASI 75, PASI 90, or PASI 100 responder were US $37,540, US $46,299, or US $80,710 for ixekizumab Q2W and US $57,533, US $120,720, or US $404,695 for etanercept BIW, respectively. US subgroup ITT population: costs per additional PASI 75, PASI 90, or PASI 100 responder were US $38,165, US $49,740, or US $93,536 for ixekizumab Q2W and US $69,580, US $140,881, or US $631,875 for etanercept BIW, respectively.

CONCLUSIONS: Twelve-week costs per additional responder were lower for ixekizumab Q2W than for etanercept BIW across all levels of clearance (PASI 75, PASI 90, and PASI 100) in the pooled UNCOVER-2/UNCOVER-3 overall and US subgroup ITT populations.

J Drugs Dermatol. 2017;16(12):1246-1252.

Background: Plaque psoriasis affects about 2% of the US population. A new and unique spray formulation of clobetasol propionate (CP) 0.05% was developed to provide advantages over the currently available treatment formulations.
Objectives: To evaluate the efficacy and safety of CP 0.05% spray compared to its vehicle in the treatment of moderate to severe plaque psoriasis.
Methods: A 4-week, single-center, randomized, double-blind, vehicle-controlled, intra-individual study in subjects with plaque psoriasis. Each of 2 target lesions per subject were randomized to receive either CP 0.05% spray or its vehicle twice daily over 4 weeks. Efficacy parameters included overall target plaque severity score, scaling, erythema, and plaque elevation at all visits. Adverse events were reported throughout the study.
Results: A total of 27 subjects were enrolled in the study. At all visits there was a significant intra-individual treatment effect for the overall target plaque severity (P<.001) in favor of CP spray. Throughout the study, results for scaling, erythema, and plaque elevation were significantly (P<.001) in favor of CP spray. After 4 weeks of treatment, all intra-individual response measures, with the exception of erythema, showed an average difference in severity scores of more than 4 points (based on a 9-point scale) between the lesions treated with CP 0.05% spray and the lesions treated with vehicle. No serious adverse event occurred during the course of the study. One local adverse event at the application site (5%) was considered probably related to study medication.
Conclusion: CP 0.05% spray was effective and safe in reducing overall plaque severity, scaling, erythema, and plaque elevation from the first week of treatment continuing throughout the trial.

Scalp lesions are common among patients with psoriasis, seborrheic dermatitis and a number of other inflammatory and fungal conditions. Topical corticosteroids are a mainstay of treatment for many scalp dermatoses and they significantly reduce erythema, scaling and pruritus. Conventional corticosteroid formulations such as cream and ointments are often difficult or time consuming for patients to apply and may produce undesirable cosmetic effects. Medicated shampoos provide a more convenient alternative for patients who require topical administration of corticosteroids for scalp conditions. Tar shampoos have long been used to treat psoriasis and are effective for the long-term maintenance of remission in patients who respond to therapy. Antifungal shampoos are effective for the treatment of seborrheic dermatitis and other mycotic conditions. A shampoo formulation containing fluocinolone acetonide, 0.01% is also approved for the treatment of seborrheic dermatitis. One superpotent corticosteroid shampoo (clobetasol propionate 0.05%; Clobex® Shampoo) is approved in the United States (U.S.) for once-daily treatment of psoriasis of the scalp. The results of a 2007 pilot study also demonstrated that clobetasol propionate shampoo improved the signs and symptoms of seborrheic dermatitis. These findings suggest that high-potency corticosteroid shampoos may provide an important option for topical corticosteroid therapy in dermatologic conditions affecting the scalp

INTRODUCTION: Biologic therapies have revolutionized the treatment of psoriasis; however, their use is limited by costs. Ixekizumab was more effective than etanercept in the UNCOVER trials, and the Food and Drug Administration (FDA) approved ixekizumab for treating psoriasis. Evaluating the cost-effectiveness of these therapies is crucial for medical decision making and our objective was to determine the cost-effectiveness of various ixekizumab dosing frequencies compared with etanercept. METHODS: We utilized published data from the UNCOVER comparative efficacy trials, including transitional probabilities and treatment response rates, to create a Markov model simulating the clinical course and cost-effectiveness of three treatment algorithms for patients with moderate to severe plaque psoriasis over 60-weeks: (1) ixekizumab every 2 weeks for 12 weeks then every 4 weeks, (2) ixekizumab every 4 weeks throughout the treatment period, (3) biweekly etanercept for 12 weeks then once weekly. We utilized a standard willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) and Medicaid drug acquisition costs for our calculations. RESULTS: Ixekizumab every 4 weeks was $28,681 (USD) less expensive than biweekly etanercept, and $21,375 less expensive, and 0.006 QALY less effective, than ixekizumab every 2 weeks-- a savings of $28.7 and $21.4 million, respectively, per 1,000 patients. A 95.6% cost reduction to $197.83 per dose is required for ixekizumab every 2 weeks to be more cost-effective than every 4 weeks. Biweekly etanercept requires a 29.5% cost reduction ($743.82 per dose) to be competitive with ixekizumab every 4 weeks. DISCUSSION: This cost-effectiveness model utilizes strong input data but is a limited approximation of real-life scenarios. Treatment with ixekizumab every 2 weeks is unlikely to be cost-effective compared with ixekizumab every 4 weeks at current U.S. market prices. Yet, the U.S. FDA approval and manufacturer’s recommendation are for ixekizumab every 2 weeks. Accordingly, we suggested selecting biologic therapies using cost-effectiveness analyses.

J Drugs Dermatol. 2017;16(10):964-970.

BACKGROUND: An issue in long-term clinical trials of biologics in psoriasis is how to handle missing efficacy data. This methodological challenge may not be understood by clinicians, yet can have a significant effect on the interpretation of clinical trials.

OBJECTIVE Evaluate the effects of different data imputation methods on apparent secukinumab response rates.

METHODS: Post hoc analyses were conducted on efficacy data from 2 phase III, multicenter, randomized, double-blind trials (FIXTURE and ERASURE) of secukinumab in moderate to severe plaque psoriasis. Per study protocols, missing data were imputed using strict non-response imputation (NRI), a highly conservative method that assumes non-response for all missing data. Alternative imputation methods (observed data, last observation carried forward [LOCF], modified NRI, and multiple imputation [MI]) were applied in this analysis and the resultant response rates compared.

RESULTS: Response rates obtained with each imputation method diverged increasingly over 52-weeks of follow-up. Strict NRI response estimates were consistently lower than those using the other methods. At week 52, Psoriasis Area and Severity Index (PASI) 90 rates for secukinumab 300 mg based on strict NRI were 9.2% (FIXTURE) and 8.7% (ERASURE) lower than estimates obtained using the least conservative method (observed data). Estimates obtained through LOCF and modified NRI were closest to those produced by MI, currently regarded as the most methodologically sophisticated approach available.

CONCLUSION: Awareness of differences in assumptions and limitations among imputation methods is necessary for well-informed interpretation of trial data.

J Drugs Dermatol. 2017;16(8):734-742.

INTRODUCTION: Psoriasis has a major impact on patient quality of life, similar to that seen in other chronic diseases, eg, diabetes. Health-related quality of life (HRQoL) measures are commonly included in clinical trial designs, capturing the disease burden and therapeutic success of a treatment. In the randomized, double-blind, phase III PSO-FAST (Psoriasis vulgaris, a Four-week, vehicle-controlled, efficacy And Safety Trial) study (nCT01866163), fixed combination calcipotriene (Cal) 0.005% plus betamethasone dipropionate (BD) 0.064% aerosol foam was compared with vehicle. By treatment end, 53% of patients using Cal/BD foam achieved treatment success.
OBJECTIVE: To compare the impact on HRQoL of Cal/BD foam vs vehicle in patients with mild-to-severe psoriasis.
METHOD: HRQoL was assessed by dermatology life-quality index (DLQI; baseline, weeks 1, 2, 4) and EQ-5D-5L (EQ-5D; baseline, week 4) questionnaires. A DLQI score of 0 (range, 0–30) indicates no effect on the patient’s life; an EQ-5D utility score of 1 (range, 0–1) and an EQ-5D visual analog scale (VAS) score of 100 (range, 1–100) indicate perfect health.
RESULTS: 426 patients were randomized (Cal/BD foam, n=323; vehicle, n=103). Baseline mean DLQI scores were 9.9 (Cal/BD foam) and 10.3 (vehicle). The impact of psoriasis on HRQoL (EQ-5D utility score) at baseline was primarily driven by pain/discomfort (Cal/BD foam: 69.9%; vehicle: 65.0%) and anxiety/depression (Cal/BD foam: 45.3%; vehicle 44.7%). There was a greater improvement from baseline in DLQI score for Cal/BD foam vs vehicle at week 4 (–7.0 vs –4.4; P<.001); increased improvement was also seen in EQ-5D scores. At week 4, 48.1% of patients using Cal/BD foam reported no effect of psoriasis on their lives (DLQI = 0/1), and of patients using Cal/BD foam with baseline DLQI scores ≥5, 81.2% achieved a ≥5-point improvement.
CONCLUSION: Cal/BD aerosol foam improved HRQoL after 4 weeks, with most patients experiencing a clinically meaningful improvement and almost 50% reporting no impairment.

J Drugs Dermatol. 2016;15(8):981-987.

This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thriceweekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thriceweekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related to the use of any newly available product. In particular, surveillance should focus on the immunomodulating biologic agents in order to identify possible dangerous sequelae. (J Drugs Dermatol. 2011;10[1]80-83.)

No abstract details for the moment.

Etanercept is approved for the treatment of plaque psoriasis at a subcutaneous (SC) dosage of 50 mg twice-weekly for three months, followed by 50 mg SC once-weekly thereafter. It is of note, however, that many patients experience loss of efficacy when they step down to etanercept 50 mg/week, often instigating a switch to another biological. The current pilot study investigated the adjunctive use of a topical calcipotriene 0.005% and betamethasone dipropionate 0.064% combination ointment, approved for the treatment of psoriasis, to sustain the original efficacy of etanercept by augmenting response to the 50 mg/week SC dose, thus stabilizing the disease.
Trial Design: In this single-center, open-label study, subjects (n=20) underwent 12 weeks treatment with etanercept 100 mg/week (50 mg, 2x week; weeks –12 to -1), followed by etanercept 50 mg/week maintenance therapy for 40 weeks (weeks 0 to 40). Subjects were followed at four-week intervals. Starting at week 4, subjects who demonstrated an increase from baseline (week 0) body surface area (BSA) of >2% initiated therapy with calcipotriene 0.005% and betamethasone dipropionate 0.064% ointment for four weeks. The study is limited by its small sample size, open-label nature, and lack of blinding.
Findings: Mean BSA involvement decreased significantly from week –12 to 0 with etanercept 50 mg twice a week. At week 4, on the etanercept 50 mg/week dose, mean BSA increased to 9.42±9.39 compared to week 0. With introduction of calcipotriene 0.005%/betamethasone dipropionate 0.064% ointment at week 4, mean BSA decreased to 4.62±8.19 by week 24 and was relatively stable for the remainder of the study period. Similarly, mean PASI (Psoriasis Area and Severity Index) scores improved from week -12 to week 0, increased at week 4, then decreased significantly by week 24 with adjunctive topical treatment.
Conclusion: Topical calcipotriene 0.005% and betamethasone dipropionate 0.064% ointment is a safe and effective adjunct to etanercept 50 mg/week maintenance therapy.

J Drugs Dermatol. 2011;10(8):881-885.

Etanercept is a dimeric fusion protein that has been approved for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis and moderate to severe plaque psoriasis. It has been reported to be useful in other variants of psoriasis, Still’s disease, recurrent aphthous ulcers, and a variety of rare cutaneous conditions. Its cutaneous side effects are rare and include injection site reactions, cutaneous lupus, and cutaneous vasculitis. Its systemic side effects are also rare and include induction or worsening of infections, lupus, multiple sclerosis, and congestive heart failure. Linkage to an increased risk of lymphoma is unclear. In short, etanercept is a promising medication with substantial benefits and use will probably increase in the future. This review surveys off-label uses and side effects of etanercept.

BACKGROUND: Little is known about the impact of long-term use of immunosuppressive agents on immune response.
OBJECTIVES: Assess the impact of continuous maintenance ustekinumab treatment on patients' ability to mount immune responses to pneumococcal (T-cell-independent) and tetanus toxoid (T-cell-dependent) vaccines.
PATIENTS and METHODS: Ustekinumab-treated patients with moderate-to-severe psoriasis treated in the long-term extension of the Phase 3 PHOENIX 2 trial (n=60) were compared with control psoriasis patients not receiving systemic therapy (n=56). Patients were vaccinated with both 23-valent pneumococcal and tetanus toxoid vaccines. Serum samples collected pre-vaccination and 4 weeks post-vaccination were assessed for antibody responses.
RESULTS: No differences in the ability of ustekinumab-treated patients to respond to pneumococcal or tetanus toxoid vaccinations were observed compared with controls. A ≥2-fold increase in antibody levels in ≥7 of 14 serotypes of the pneumococcal vaccine was observed in ustekinumab-treated (96.6%) and untreated control (92.6%) patients following vaccination. Ustekinumab-treated patients achieved a ≥4-fold increase (84.7%) in anti-tetanus antibody vs. 77.8% in the control group. No differences were detected in ex-vivo responses to anti-CD3/CD28 or tetanus toxoid between ustekinumab-treated and control groups.
CONCLUSION: Long-term treatment (≥3 years) with ustekinumab does not compromise the immune response to T-cell-dependent/-independent vaccines in patients with moderate-to-severe psoriasis.

J Drugs Dermatol. 2013;12(10):1122-1129.

Hereditary punctate palmoplantar keratoderma (Buschke-Fischer-Brauer disease) is a rare disorder of keratinization. We describe here a 49-year-old male patient of this condition with many unusual features such as late onset of the disease in the fourth decade and nail changes (longitudinal pigmented striations, curved nails and pits in the fingernails; and nail thickening, subungual hyperkeratosis and yellowish discoloration in toenails). The patient developed histopathologically proven skin lesions typical of psoriasis 7 years after appearance of the keratoderma. This association has not been reported earlier. The patient’s skin lesions cleared completely with acitretin therapy within 3 months.

We present the case of a female, aged 22 years, with a long history of recalcitrant pustular psoriasis and psoriatic arthritis, treated with ustekinumab during pregnancy. The result of treatment was an uncomplicated pregnancy with delivery, at term, of a healthy boy. To our knowledge, this is the first reported use of ustekinumab in a human during pregnancy. Following a description of the case, we discuss the characteristics of ustekinumab and review the known information from human case reports, case series, and animal studies regarding the use of TNF-α inhibitors and ustekinumab during pregnancy. We also provide a short discussion of administration of ustekinumab during the time period when a mother is nursing and the potential for complications to infants in this setting.

J Drugs Dermatol. 2012;11(10):1240-1241.

Retinoids, a group of compounds encompassing Vitamin A and its analogs, have been shown to inhibit tumor growth in laboratory studies. Based on these findings, a number of clinical trials have been conducted to investigate the chemoprotective and chemotherapeutic effects of retinoids. This paper reviews the current database regarding the use of oral and topical retinoids in the prevention and treatment of cutaneous and internal malignancies. Clinical studies have shown that retinoids have beneficial effects in the prevention and treatment of certain neoplasms. In view of the heightened concern of malignancy associated with the use of biologic agents in the treatment of psoriasis, retinoids may be an attractive option for combination therapy with the biologic agents. Future clinical investigations are needed to precisely define how this combination will fit into the treatment algorithm for moderate-to-severe psoriasis.

No abstract details for the moment.

BACKGROUND: Apremilast, a small molecule specific inhibitor of phosphodiesterase 4, works intracellularly to modulate pro-inflammatory and anti-inflammatory mediators. This phase II, multicenter, open-label study evaluated the efficacy, tolerability, and pharmacodynamics of apremilast in patients with recalcitrant plaque psoriasis.
METHODS: This multicenter, open-label study comprised four phases: pre-treatment (≤35 days), treatment (12 weeks), extension (12 weeks), and observational follow-up (4 weeks). Patients with recalcitrant plaque psoriasis received apremilast 20 mg BID for 12 weeks. Responders (≥75% improvement in Psoriasis Area and Severity Index [PASI-75]) continued treatment and non-responders (< PASI-75) were titrated to apremilast 30 mg BID through week 24. Efficacy assessments included change in static Physician's Global Assessment, PASI, and body surface area, and proportion of patients achieving PASI-50, PASI-75, and PASI-90. Other assessments included adverse events, lesional skin biopsies to assess changes in epidermal thickness, and immunohistochemistry to assess changes in peripheral blood subsets.
RESULTS: A total of 30 patients were enrolled. At week 12, 67% of patients had a ≥1-point improvement in static Physician’s Global Assessment, meeting treatment effect criterion. Mean percent decreases (improvements) from baseline were –59% for PASI score and –53% for body surface area. Most adverse events were mild. Median reduction in epidermal thickness was 34% at week 12 (P=0.083); five patients showed absence of keratin 16. Significant reductions in CD11c, CD3, and CD56 indicate that apremilast reduced myeloid dendritic cell, T-cell, and NK-cell or NK–T-cell infiltration into the epidermis and dermis. Reduced inflammatory leukocytes, with a pattern of broad, partial inhibition, suggested reduced IL-23/Th17 and Th22 response pathways.
CONCLUSIONS: These results confirm apremilast's biological and clinical activity and support ongoing studies in psoriasis. Clinicaltrials.gov Identifier: NCT00521339.

J Drugs Dermatol. 2013;12(8):888-897.

No abstract details for the moment.

With the recent data showing that psoriasis patients are at higher risk for systemic malignancies, there is a growing awareness for the need to minimize cancer risks in psoriasis patients. Retinoids as a class of medication have been widely studied as potential agents for cancer chemoprevention. Since they act by inducing cell differentiation and maturation, they may help reverse the pathogenesis of malignancies. Through an extensive literature review, this paper provides an update on the available data on retinoids and their systemic anti-cancer properties. Retinoids appear to be beneficial in the prevention of cutaneous T-cell lymphoma, acute promyelocytic leukemia, head and neck cancers, hepatocellular carcinoma, breast cancer and neuroblastoma. So far the data does not support anti-cancer efficacy of retinoids in the prevention of prostate or pancreatic cancer and may possibly have harmful effects in the pathogenesis of lung cancer in smokers.

J Drugs Dermatol. 2011;10(11):1292-1298.

BACKGROUND: Biologic patent expiration, accelerated approval pathways, and business interests of third party payers and the biopharmaceutical industry are driving the development of biosimilars to treat immune-mediated disorders like psoriasis. No studies have investigated dermatologists’ familiarity and perspectives of biosimilars.

OBJECTIVES: To assess: (1) dermatologists’ familiarity with biosimilars and interchangeability and (2) their perspectives toward biosimilar properties, including interchangeability, indication extrapolation, and immunogenicity risk.

METHODS: For this prospective survey study, we distributed electronic and paper questionnaires to dermatologists from selected societies and attendees at the 73rd annual American Academy of Dermatology meeting between March 20, 2015 and May 30, 2015. Primary outcome was dermatologists’ familiarity with biosimilars. Secondary aims included dermatologists’ confidence in biosimilar efficacy and safety, familiarity concerning the concept of interchangeability and perspectives regarding indication extrapolation, interchangeability, and immunogenicity risk.

RESULTS: Of the 116 total dermatologists who completed the questionnaire, 73 (62.9%) were slightly to very unfamiliar with biosimilars. On a 5-point Likert scale, dermatologists were somewhat to very concerned with the practice of interchangeability (3.4±1.1) and slightly uncomfortable to fairly comfortable in prescribing biosimilars for an extrapolated indication (3.3±1.0).

CONCLSUIONS: Our survey identified that the majority of dermatologists were unfamiliar with biosimilars. Dermatologists were consistently concerned regarding safety issues surrounding the practice of interchangeability without provider knowledge.

J Drugs Dermatol. 2017;16(4):336-343.

Statins, initially developed as antimicrobials, are primarily considered cholesterol-lowering agents. Recently, researchers discovered anti-inflammatory properties of statins. Studies on the effects of statins and the alterations noted include: bench work that supported a Th1/Th2 skew to Th1, altered lymphocyte migration, inhibition of MHC-II induction and cytokine release on antigen-presenting cells, inhibition of mast cell degranulation and inhibition of Th17 cells and IL-17 production. In addition to the anti-inflammatory properties, statins have been found to induce apoptosis in melanoma models. The potential therapeutic value of statins is illustrated in the management of alopecia areata, atopic dermatitis, psoriasis, systemic lupus erythematosus, cutaneous T-cell lymphomas, cutaneous melanoma, mastocytosis and more. This manuscript presents a comprehensive review of statins and their potential dermatologic application.

BACKGROUND: CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients.
OBJECTIVE: To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis.
METHODS: This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level.
RESULTS: CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%).
CONCLUSIONS: Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment.

J Drugs Dermatol. 2016;15(8):931-938.

No abstract details for the moment.

Clinicians treating corticosteroid-responsive dermatoses, such as eczema and atopic dermatitis, contact dermatitis, seborrheic dermatitis, and psoriasis, have numerous treatment options. The decision to choose a topical corticosteroid depends on several different factors, such as potency, formulation, dosage, cosmetic elegance, cost, etc. Among these, Promius Pharma's Cloderm (clocortolone pivalate cream 0.1%) was introduced into the market more than 3 decades ago, and it remains a versatile treatment option for dermatoses. Phase 3 clinical trial data have demonstrated the efficacy and tolerability of Cloderm in several steroid responsive dermatoses. In studies for eczema and atopic dermatitis, statistically significant improvement relative to placebo was seen at day 4 with Cloderm. In psoriasis trials, Cloderm cream demonstrated superiority to placebo by day 7, continuing at days 14, 21, and 28. Thus, Cloderm's early onset of action will contribute to increased compliance for patients.

BACKGROUND: Treatment with calcipotriene plus betamethasone dipropionate (CBD) fixed-combination topical suspension has been shown to be effective and well tolerated in patients with psoriasis vulgaris.
AIM: To document experiences with CBD topical suspension in a US clinical dermatology setting using patient-reported outcomes (PROs).
METHODS: In total, 147 patients were enrolled in this 8-week, prospective, noninterventional, multicenter, one-arm study. Data were collected at baseline and week 8 at the office, and at one time at home (week 2). PROs were assessed using the Dermatology Life Quality Index (DLQI), Patient’s Global Assessment of disease severity (PtGA) using a 5-point Likert scale, patient-reported level of itching using a 0–100 graduated visual analog scale, and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Treatment adherence and adverse events (AEs) were assessed at week 8.
RESULTS: After 8 weeks of treatment, DLQI score significantly improved compared with baseline (–5.5 ± 5.93; P<.0001), starting as early as week 2 (–4.2 ± 5.28; P<.0001). The level of itching was significantly reduced from baseline to week 2 (–19% ± 25.94%; P<.0001) and week 8 (–28.6% ± 29.14%; P<.0001). The percentage of patients with “controlled disease” (PtGA score of “clear” or “very mild”) was 34.1% at week 2 and 60.2% at week 8. At the end of treatment, mean TSQM-9 scores for effectiveness, convenience, and satisfaction domains ranged from 68 to 74. Patients reported the need to use CBD topical suspension for an average of 53.62 ± 8.05 days. Treatment-emergent AEs occurred in 3 patients.
CONCLUSION: The results of this noninterventional study are consistent with previously reported data from interventional trials and suggest that treatment with CBD topical suspension is efficacious and well tolerated and improves quality of life in patients with psoriasis vulgaris.

J Drugs Dermatol. 2014;13(11):1374-1379.

No abstract details for the moment.

BACKGROUND: Tofacitinib is a Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis. We report efficacy of tofacitinib in patient subgroups based on pooled data from two Phase 3 trials (NCT01276639, NCT01309737).
OBJECTIVES: To assess consistency of treatment effects of tofacitinib versus placebo in subgroups defined by baseline characteristics, and to ascertain whether baseline characteristics are of value in optimizing tofacitinib use.
METHODS: Pooled data from the two trials were used to evaluate ≥75% reduction in PASI from baseline (PASI75 response) in subgroups defined by age, age at psoriasis onset, gender, race, geographical region, weight, body mass index, diabetes, metabolic syndrome, tobacco/alcohol use, psoriatic arthritis, disease activity, and prior therapy.
RESULTS: Week 16 PASI75 response rates (N=1843) were 43%, 59% and 9% with tofacitinib 5 and 10mg twice daily (BID) and placebo, respectively (each P<0.0001 versus placebo). Tofacitinib 5 and 10mg BID were effective regardless of baseline characteristics. Across subgroups, tofacitinib generally produced greater response rates with the 10 versus 5mg BID dosage. Lower absolute response rates were seen in heavier patients and patients with prior biologic experience.
CONCLUSIONS: Both tofacitinib dosages demonstrated consistent efficacy versus placebo across subgroups. Lower response rates were seen in heavier patients and those with prior biologic experience. Tofacitinib 10mg BID resulted in a substantial proportion of responders regardless of baseline characteristics.

J Drugs Dermatol. 2016;15(5):568-580.

BACKGROUND: Long-term data are essential to assess the safety of biologic agents for the treatment of psoriasis.
OBJECTIVE: To evaluate the incidence of adverse events of interest (AEIs), including all-cause mortality, major adverse cardiovascular events (MACE), malignancy (excluding nonmelanoma skin cancer), and serious infections (SI), in patients treated for psoriasis in clinical practice settings.
METHODS: PSOLAR is a large, ongoing, observational study of patients receiving, or eligible to receive, biologic or systemic therapy for psoriasis. Cumulative incidence rates of AEIs per 100 patient-years (PY) are reported across treatment cohorts: (1) infliximab, (2) ustekinumab, (3) other biologics (eg, adalimumab and etanercept), and (4) non-biologic agents. Significant predictors of each AEI were identified using Cox proportional hazards regression methodology.
RESULTS: PSOLAR is now fully enrolled at 12095 patients followed for 31818PY. The cumulative rate was 0.46/100PY for death, 0.36/100PY for MACE, 0.68/100PY for malignancy, and 1.50/100PY for SI. Increasing age was a significant predictor of all AEIs. A history of cardiovascular disease, malignancy, and significant infection was associated with a higher risk of developing MACE, malignancy, and SI, respectively. Exposure to infliximab (Hazard Ratio [HR]=3.101, P<0.001) and exposure to other biologics (HR=1.736, P<0.001) were significant predictors of SI. Use of immunomodulators (HR=1.954, P=0.005) was a significant predictor of MACE. Compared with non-biologic therapy, the use of biologic agents was not a significant predictor of death, MACE, or malignancy.
CONCLUSIONS: Based on PSOLAR data through 2013, no new safety concerns were observed with infliximab for all-cause mortality, MACE, or malignancy; the data suggest that infliximab was associated with serious infections.

J Drugs Dermatol. 2014;13(12):1441-1448.

Background: The PEARL study showed that the proportion of psoriasis patients achieving the primary endpoint (at least 75% improvement from baseline to week 12 in the Psoriasis Area and Severity Index) was significantly higher in ustekinumab-treated patients compared with placebo. There is a paucity of data regarding the impact of psoriasis and its treatment on health-related quality of life (HRQoL) in Asian patients.
Objectives: To evaluate the effect of ustekinumab on HRQoL in Korean/Taiwanese patients with moderate to severe psoriasis enrolled in the phase III, randomized, double-blind, placebo-controlled PEARL study.
Methods: In the PEARL study, 121 patients were randomized to receive ustekinumab 45 mg at weeks 0, 4, and 16 (n=61) or placebo at weeks 0 and 4 with crossover to ustekinumab at weeks 12 and 16 (n=60). A major secondary endpoint was the change in Dermatology Life Quality Index (DLQI) from baseline at week 12. Other endpoints included the change in individual DLQI domains, proportion of patients achieving DLQI ≤ 1 (no negative effect), and proportion of patients achieving ≥ 5-point reduction in DLQI (clinically meaningful improvement) at week 12.
Results: At baseline, psoriasis had a very large effect on HRQoL (average DLQI, 15.7). At week 12, patients treated with ustekinumab 45 mg had significantly greater improvement from baseline in DLQI scores compared with placebo (mean decrease, 11.2 vs 0.5 (P<0.001). Likewise, 32.2% and 1.7% of patients receiving ustekinumab 45 mg and placebo, respectively, achieved a DLQI ≤ 1, and 81.4% and 18.3% achieved ≥5-point reduction (both P<0.001 vs placebo). Individual DLQI domains in the ustekinumab group were significantly improved compared with placebo (P<0.001). For ustekinumab-randomized patients, HRQoL improvements were sustained through week 28. Placebo patients who crossed over to ustekinumab experienced similar improvements compared with those randomized to ustekinumab.
Conclusions: Ustekinumab significantly improves HRQoL in Korean/Taiwanese patients with moderate to severe psoriasis.

J Drugs Dermatol. 2012;11(8):943-949.

Bupropion is a very popular medication prescribed to millions of patients globally for depression (Wellbutrin®, GlaxoSmithKline, Research Triangle Park, NC) as well as an aid in smoking cessation (Zyban®, GlaxoSmithKline, Research Triangle Park, NC). It has been reported to have some common dermatologic side effects, such as pruritus, urticaria and serum-sickness like reaction. The authors report a case of bupropion-induced Stevens-Johnson syndrome (SJS) with a concomitant acute psoriatic exacerbation in a 56-year-old woman, who began taking bupropion for treatment of depression. While the United States (U.S.) prescribing information for bupropion does include SJS as a rare potential side effect, it does not mention worsening of psoriasis. Physicians should be aware of the potential life-threatening adverse effects of this commonly prescribed medication as well as the risk in patients with known psoriasis.

Infliximab is a chimeric monoclonal antibody to TNF-α which acts on both the soluble and transmembrane forms of TNF-α. It has been used successfully for the treatment of psoriasis and psoriatic arthritis, rheumatoid arthritis, Crohn’s disease and ankylosing spondylitis either as monotherapy or in combination with drugs such as methotrexate. To date, over 20,440 patients with moderate-to-severe psoriasis have been treated with infliximab worldwide. Opportunistic infections and reactivation of underlying latent infections are an area of concern with the use of infliximab particularly when used in conjunction with other immunosuppresants. The authors report a case of histoplasmosis presenting with signs of severe hypercalcemia and renal failure in a patient on infliximab for approximately three years in combination with low dosages of methotrexate and prednisone. This report stresses the importance of maintaining a high index of suspicion for unusual pathogens while managing patients receiving TNF-α inhibitors, particularly when used in combination with other immunosuppressants. In addition, the authors emphasize the role of a multi-disciplinary approach and appropriate coordination among caregivers.

Intra-subject, left-right, randomized, controlled study designs are often used for proof-of-concept studies in dermatology. This design was used to evaluate the safety and efficacy of a topical solution of tofacitinib (NCT00678561), a small-molecule Janus kinase inhibitor under investigation for the topical and oral treatment of patients with chronic plaque psoriasis. Eighty-one patients, each with matched left and right target plaques, were randomized to 2%, 0.2%, or 0.02% tofacitinib or vehicle solution once or twice daily. Patients treated one plaque as per their randomization group (2%, 0.2%, 0.02% tofacitinib, or vehicle solution), and used vehicle to treat the contralateral plaque for 4 weeks. Except during clinic visits, study drug applications were performed unsupervised outside the clinical trial site. Intra-subject, vehicle-adjusted mean percent change from baseline in Target Plaque Severity Score at week 4 (primary efficacy endpoint) was not significantly different from baseline for any treatment group (P values of 0.28–0.68). However, skin biopsy analyses detected tofacitinib in both tofacitinib- and vehicle-treated plaques of some patients, suggesting cross-contamination or solution misapplication. Lack of efficacy with tofacitinib relative to vehicle may be due to the intra-subject study design with unsupervised applications. These findings have potential implications for future intra-subject studies of topical treatments.

J Drugs Dermatol. 2015;14(8):777-784.

Tumor necrosis factor-α (TNF-α) inhibitors are biologic agents that are currently in wide use for the treatment of psoriasis as well as other inflammatory diseases. Following reports of thrombocytopenia as a potential adverse effect of anti-TNF-α therapy, we performed a retrospective study to determine the frequency of thrombocytopenia, defined as a platelet count <50x109 cells/L, in a cohort of 187 psoriatic patients treated with anti-TNF-α agents over a nine-year period. Although none of our patients met serologic criteria for thrombocytopenia or displayed clinical manifestations of thrombocytopenia, two patients developed platelet counts below 100×109 cells/L. Thrombocytopenia induced by anti-TNF-α agents is a potential adverse effect, it is a rare occurrence that will require further investigation in large, placebo-controlled, double-blind, prospective studies.

J Drugs Dermatol. 2011;10(3):280-284.

Background: The efficacy and safety profile of ustekinumab with up to three years of exposure suggested a favorable benefit-risk profile in patients with moderate to severe psoriasis.
Objective: To evaluate the safety of ustekinumab in patients with moderate to severe psoriasis treated for up to four years.
Methods: Safety data were pooled across four Phase II/III randomized controlled trials. Rates over time and cumulative rates of adverse events (AEs), AEs leading to treatment discontinuation, serious adverse events (SAEs), serious infections, malignancies, and major adverse cardiovascular events (MACE) (i.e., cardiovascular death, myocardial infarction [MI], or stroke as adjudicated by an independent panel of academic cardiologists) were evaluated. Observed rates of AEs of interest were compared with those expected in the general (malignancies, MI, and stroke) and psoriasis (serious infections, MI, and stroke) populations.
Results: Overall, 3,117 patients were followed for up to four years (6,791 patient-years). Rates of AEs, AEs leading to treatment discontinuation, and SAEs remained stable over time, whereas cumulative rates were generally comparable between patients who received 45 mg and 90 mg of ustekinumab. The rates of AEs of interest also remained stable over time, and cumulative rates per 100 patient-years were 0.80 and 1.32 (serious infections), 0.70 and 0.53 (nonmelanoma skin cancer), 0.63 and 0.61 (other malignancies), and 0.56 and 0.46 (MACE) in patients treated with 45 mg and 90 mg, respectively. Rates of AEs of interest were consistent with those in the general and psoriasis populations.
Conclusion: The safety profile of long-term ustekinumab treatment with up to four years of continuous use remains consistent with previous reports, with no evidence of cumulative toxicity.

J Drugs Dermatol. 2012;11(3):300-312

Topical treatment of resistant psoriatic plaque stage lesions may be diffi cult and the systemic therapies seem inappropriate. There- fore, a topical 0.1% methylene blue (MB) hydrogel was prepared and evaluated for percent drug content, drug uniformity, pH, rheo- logical and organoleptic characters such as feel tackiness, grittiness sensation, and transparency in addition to release kinetics study in vitro. The effi ciency of the photodynamic therapy (PDT) of MB photo-activated using 565 mW Light emitting diode (LED) 670 nm was evaluated in patients with resistant plaque psoriasis. The gel was evaluated in single blinded study. The patients were subjected to repeated sessions of irradiation, skin biopsies from each patient in the beginning and at the end of the sessions were taken for histopathological studies. Results showed the hydrogel was transparent nongritty and the drug uniformly dispersed with pH=7.2 and viscosity value= 25.04 Pa. The drug content was found to be 99.4 ± 0.15 %. Drug release was following zero order kinetics with rate constant K= 0.348 ± 0.01 and T 1\2 = 0.95±0.5 hours. Sixteen patients experienced complete clearance of their treated lesions. Skin appeared normal in color, texture, and pliability with no complications indicating the lack of skin sensitivity. Histopathological examina- tions showed nearly normal epidermis at the end of all sessions. The authors concluded that the prepared hydrogel was safe, stable, and very effective. The results are encouraging to accept MB as a photosensitizer for PDT and as a safe and effective method for treatment of selected cases of resistant localized psoriasis.

Objectives: Psoriasis is a chronic inflammatory condition that occurs worldwide; however, few studies have examined this condition in non-Caucasian populations. The purpose of this study was to investigate racial/ethnic differences in demographics, psoriasis severity, efficacy, safety, and health-related quality of life in patients treated with etanercept using data from the Etanercept Assessment of Safety and Effectiveness (EASE) in Psoriasis trial.
Patients and Methods: This is an investigator-initiated evaluation of data from the EASE study.
Results:The study included 2511 patients (Caucasian n=2164; Hispanic/Latino n=173; African American n=98; Asian n=76). Although baseline Physicians' Global Assessment (PGA) scores were similar, we found significant baseline differences in patient characteristics, prior therapy, percentage of body surface area (%BSA) affected and Dermatology Life Quality Index (DLQI) scores between the groups. At baseline, the Caucasian group had the longest disease duration (19 years), but the lowest percentage of BSA involvement (28%). The Asian group had the highest percentage of BSA involvement (41%). Baseline DLQI score was lowest for Caucasians (12.0) and highest for Hispanic/Latinos (14.6).
At week 12, response to therapy was similar in all ethnic/racial groups. The BSA involvement was reduced by more than 50 percent for all groups, but remained significantly higher for the Asian group (17%) than for the Caucasian (13%; P=0.0105) and African American groups (13%; P=0.0461).
At week 12, the mean Asian DLQI score of 5.2 was significantly higher (worse) than scores for the Caucasian (3.5; P=0.0001) and Hispanic/Latino groups (3.8; P=0.028). For both percentage of BSA and DLQI, differences among racial/ethnic groups in the percentage improvement from baseline were not statistically significant. Adverse event rates were similar for the groups.
Conclusions:Patient characteristics at enrollment differed among ethnic groups, but no significant racial/ethnic differences were found in safety or efficacy of etanercept. However, racial/ethnic differences in the impact of psoriasis on quality of life were observed.

J Drugs Dermatol. 2011;10(8):862-868.

Progressive multifocal leukoencephalopathy (PML) is a rare neurological disorder that occurs almost exclusively in immunocompromised individuals by reactivation of the John Cunningham virus (JC virus), a polyomavirus found latent in more than 80 percent of healthy adults. Efalizumab, an immunosuppressive monoclonal antibody targeting T cells, has been used for treatment of moderateto- severe chronic psoriasis. The authors describe two cases of PML that occurred in patients ≥70 years old treated with efalizumab for more than three years. Both presented with symptoms resembling cerebral infarction (slurred speech, reduced motor control, personality changes) and were assessed for evidence of stroke. Multiple magnetic resonance images over successive weeks demonstrated progression of cerebral abnormalities. PML was diagnosed, and the presence of JC virus was confirmed in spinal fluid samples. Both patients died shortly after diagnosis. Dermatologists treating patients with immunosuppressive agents should be alert for the symptoms of PML and seek immediate consultation with a neurologist should symptoms arise.

Acitretin, a metabolite of the aromatic retinoid etretinate, has been utilized successfully in the treatment of psoriasis since the late 1980s. Of the oral retinoids available, etretinate and acitretin are the most likely agents to induce various dose-dependent hair changes, but to our knowledge this is the first reported case of acitretin-induced poliosis. Additional cutaneous findings included skin atrophy and stickiness. Here we report a case of full body acitretin-induced poliosis with concurrent alopecia in a patient with psoriasis. A proposed mechanism for the poliosis is also presented here. Closer examination of retinoid-induced hair changes is needed in order to help physicians better counsel their patients regarding the adverse effects of acitretin and to expand the current knowledge on hair follicle biology.

J Drugs Dermatol. 2012;11(2):247-249.

BACKGROUND: Changes in the composition of microbial communities that colonize skin have been linked to several diseases including psoriasis. Nevertheless, the intra-individual dynamics and how these communities respond to balneotherapy remain poorly understood.
METHODS: This open label study was conducted between July and September 2012. Microbial communities of patients with psoriasis vulgaris were characterized prior and post a 3-week selenium-rich water balneotherapy treatment at the thermal care center La Roche-Posay (La Roche-Posay, France). Balneotherapy consisted of high-pressure filiform showers, baths, facial, and body spray treatments as well as La Roche-Posay thermal spring water (LRP-TSW) consumption. Swabs were taken from affected and proximal unaffected skin and the 16S rRNA bacterial gene was used to analyze the composition of bacterial communities. Using the same 16S rRNA gene tool, we tried to describe the LRP-TSW bacterial landscape.
RESULTS: This study included 54 patients diagnosed with moderate to severe forms of psoriasis vulgaris. After eliminating individuals lacking paired samples from both visits, 29 individuals were analyzed for their microbiome profile. Shannon Diversity Index and global bacterial landscape indicate similar microbial communities on both unaffected and adjacent affected skin. PASI values decreased post-balneotherapy implying improvement of disease severity. No significant change in the Shannon Diversity Index was noticed at the end of the third week. The average taxonomic composition of skin microbial communities associated with unaffected and affected skin of psoriatic patients post-balneotherapy shows that treatment with LRP-TSW significantly increased the level of Xanthomonas genus and, to a lesser extent, Corynebacterium genus. The Xanthomonas genus belongs to the main Xanthomonadaceae family found in LRP-TSW and also on healthy skin.
CONCLUSIONS: In psoriatic patients, a poor bacterial biodiversity was noticed and the bacterial communities were similar on unaffected and affected adjacent skin. Family analysis identified, for the first time, Xanthomonadaceae belonging to Proteobacteria phylum and known to be keratolytic, associated with the clinical improvement observed after a 3-week balneotherapy treatment. This data supports the interest of selenium-rich thermal spring water in the treatment of psoriasis vulgaris.

J Drugs Dermatol. 2015;14(12):1400-1405.

A collaborative exchange of ideas occurred at The Psoriatic Disease Payer Advisory Panel sponsored by International Dermatology Outcomes Measures (IDEOM) and The National Psoriasis Foundation (NPF) in January, 2016. Patient, provider, payer, pharmaceutical industry, IDEOM board member, and NPF leader representatives shared perspectives to address the unmet needs in the treatment of psoriatic patients. The payers who play a crucial role in controlling treatment access and improving patient outcomes played a pivotal role in the discussion. Progress made during the Payer Advisory Panel will ultimately advance psoriatic initiatives and help to address the persistent challenges of all vested stakeholders.

J Drugs Dermatol. 2016;15(5):641-644.

Background: Plaque psoriasis affects about 2% of the US population. A new and unique spray formulation of clobetasol propionate (CP) 0.05% was developed to provide advantages over the currently available treatment formulations. Objectives: To evaluate the efficacy and safety of CP 0.05% spray compared to its vehicle in the treatment of moderate to severe plaque psoriasis. Methods: A 4-week, single-center, randomized, double-blind, vehicle-controlled, intra-individual study in subjects with plaque psoriasis. Each of 2 target lesions per subject were randomized to receive either CP 0.05% spray or its vehicle twice daily over 4 weeks. Efficacy parameters included overall target plaque severity score, scaling, erythema, and plaque elevation at all visits. Adverse events were reported throughout the study. Results: A total of 27 subjects were enrolled in the study. At all visits there was a significant intra-individual treatment effect for the overall target plaque severity (P<.001) in favor of CP spray. Throughout the study, results for scaling, erythema, and plaque elevation were significantly (P<.001) in favor of CP spray. After 4 weeks of treatment, all intra-individual response measures, with the exception of erythema, showed an average difference in severity scores of more than 4 points (based on a 9-point scale) between the lesions treated with CP 0.05% spray and the lesions treated with vehicle. No serious adverse event occurred during the course of the study. One local adverse event at the application site (5%) was considered probably related to study medication. Conclusion: CP 0.05% spray was effective and safe in reducing overall plaque severity, scaling, erythema, and plaque elevation from the first week of treatment continuing throughtout the trial.

Funding for the supplement provided by Galderma Laboratories, L.P..

IMPORTANCE: UV phototherapy remains a useful and frequently employed treatment for chronic plaque psoriasis. In those patients with plaque body surface area less than 10%, targeted treatment is the safest and most effective modality.
OBJECTIVE: We aimed to evaluate the efficacy of the Levia® localized NB-UVB phototherapy machine in the treatment of patients with symmetrical psoriatic lesions.
DESIGN: We performed a prospective, double-blinded, sham-treatment controlled study of this device beginning March 2012 through April 2014.
SETTING: a comprehensive dermatology clinic in the northeastern United States.
PARTICIPANTS: 21 subjects with chronic plaque psoriasis.
INTERVENTIONS: Each patient had one lesion randomized to receive the Levia treatment and one lesion (the control) treated with visible light. Treatment was administered three times a week for twelve weeks. Target lesion score (TLS), a rating of 0-4 each of erythema, scaling, and thickness, was measured biweekly by a blinded assessor, and visual analogue scale of pruritus was recorded by subjects.
MAIN OUTCOMES AND MEASURES: The primary outcome, formulated prior to study initiation, was the percentage of lesions achieving clear or almost clear TLS after 12 weeks of treatment. Secondary endpoints included changes in target lesion pruritus VAS, percentage improvement in TLS, and the percentage of subjects achieving 50% improvement in TLS (TLS-50).
RESULTS: The primary endpoint, TLS of three or less, was not achieved (P=0.118), but the secondary endpoints of percentage improvement in TLS (P=0.043) and TLS-50 (P=0.0195) were significantly superior in treated compared to sham-treated lesions. Percentage improvement in pruritus VAS was not significant (P=0.0565).
CONCLUSIONS AND RELEVANCE: This device was found to be efficacious, though not necessarily to the point of clearance, in the treatment of psoriasis over a 12-week period.
TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT02107482, http://clinicaltrials.gov/show/NCT02107482

J Drugs Dermatol. 2014;13(8):922-926.

BACKGROUND: The PASI score, the most common outcome measure in clinical trials of psoriasis treatment, is a non-linear scale that does not allow reliable assessment of subtle variations of its components (erythema, induration, and desquamation).
OBJECTIVE: Highlight treatment response patterns potentially hidden by PASI score's compounded weighted-average calculation.
METHODS: Patients with moderate-to-severe psoriasis enrolled in the phase-3, 16-week, randomized CHAMPION study, and received adalimumab, methotrexate, or placebo. PASI scores were assessed post hoc for improvement, by body region and component.
RESULTS: At Week 16, a significantly greater percentage of adalimumab-treated patients vs methotrexate- and placebo-treated patients, achieved PASI 75, PASI 90 and PASI 100 response in each body region and component. 55.7% of adalimumab-treated patients reached PASI 100 response in the head and neck region vs 16.7% overall. Two key components of PASI, induration and desquamation, were affected by treatment more than erythema, the third component. Adalimumab was particularly effective in complete resolution of induration (44.9% of patients) vs methotrexate (10.9%). For all PASI body regions and components, mean percent improvement in score at Weeks 2, 4, 8, 12, and 16 was significantly greater (P<0.05) for adalimumab treatment vs methotrexate or placebo.
CONCLUSION: Adalimumab therapy resulted in complete resolution of individual body regions in at least 30.6% up to 55.7% of patients in CHAMPION. This was more than twice that of methotrexate and placebo. PASI improvement by body region is a novel and an important patient-relevant outcome worthy of reporting in future studies.

J Drugs Dermatol. 2014;13(5):554-562.

Cyclosporine is an immunosuppressive agent that has been shown to be effective in the treatment of psoriasis. However, its serious side effects in transplant patients have hindered many dermatologists from exploiting its therapeutic capabilities. The literature contains reports of lymphomas, internal malignancies, skin cancers, and serious infections in psoriasis patients on cyclosporine therapy. However, no study has evaluated the relative risk of these side effects in relation to the general population, nor monitored the patients for years after cyclosporine was discontinued. The recently published 5-year cohort study is the most rigorous data to date on the long-term safety of cyclosporine and shows no increased risk of lymphoma or internal malignancies. The study, however, illustrates increased risk of non-melanoma skin cancers, especially squamous cell carcinoma. Review of the literature does not suggest any increased risk of opportunistic infections or tuberculosis reactivation. These data suggest that cyclosporine in dermatologic dosage (3-5 mg/kg/d) is safe and dermatologists may consider using it.

BACKGROUND: Oral methotrexate (MTX) has been a first line systemic agent in the treatment of chronic plaque psoriasis (CPP) for more than 50 years. Parenteral MTX, administered as a subcutaneous (SC) injection has gained favour in recent years. The effectiveness of SC MTX has been proven in rheumatological conditions but there has been no assessment of its role in CPP.
METHODS: We retrospectively reviewed case notes of 85 patients prescribed SC MTX for psoriasis in three dermatology centres in the UK (Betsi Cadwaladr University Health Board, Western Infirmary, Glasgow, and Salford Royal NHS Foundation Trust). Audit department approval was sought and granted.
RESULTS: A total of 85 patients (44 male; 41 female; age range 14 – 78 years, mean 44 years; 79 Caucasian, 6 Asian) with CPP were identified. The average duration of psoriasis was 19 years [range 3 - 60 years]. Co-morbidities included depression, diabetes mellitus, hypertension, epilepsy, obesity, ischaemic heart disease, and hyperlipidaemia; 29 patients had no associated co-morbidities. Psoriatic arthritis was noted in 18 patients.
Previous treatments included phototherapy (both narrow band ultraviolet B [TLO1] and psoralen and ultraviolet A [PUVA])(n=60), oral MTX (n=82), ciclosporin (n=37), acitretin (n=19), fumaric acid esters (n=20), hydroxycarbamide (n=6), mycophenolate mofetil (n=2), and repeated in-patient admissions (n=2). Oral MTX was stopped due to nausea (n=43), ineffectiveness (n=13) or partial response (n=11), headache (n=3), increased liver enzymes (n=2), and lethargy (n=2). The median number of systemic agents used prior to SC MTX was 3 (mean 2.65, range 1 to 6 agents). The weekly dose of SC MTX varied between 7.5mg to 30mg (mean 18.5mg, median 20mg) and had been used for 2 months to 67 months (mean 14 months; median 9 months). Folic acid supplementation was used in every patient. The patients were reviewed between 6 weeks to 3 months once treatment was fully established. Using a pre-determined “adjective list” (where specific adjectives were used to denote those who responded or did not respond to treatment), patients were classified as “responders” (n=59) or “non-responders” (n=26).
CONCLUSION: This study suggests that SC MTX is an effective option in patients with CPP who have failed oral MTX and could be a worthwhile consideration prior to commencement of a biologic agent. Furthermore, the SC route may be a viable first choice of MTX administration. A randomised controlled trial comparing oral and SC MTX is required to validate these findings.

J Drugs Dermatol. 2016;15(3):345-349.

Background: Alefacept is an effective intermittent treatment for psoriasis that can provide long-lasting remissions. Combination therapy with narrow-band ultraviolet B (nbUVB) phototherapy may enhance treatment outcomes and accelerate the onset of clinical response.
Objective: To assess the efficacy of alefacept in combination with nbUVB phototherapy compared to alefacept alone in subjects with moderate to severe psoriasis.
Methods: Ninety-eight adults with moderate to severe psoriasis were randomized to treatment with alefacept 15 mg intramuscularly (IM) once weekly for 12 weeks alone or in combination with three times weekly nbUVB treatments in this prospective, open-label, assessor-blinded, randomized, multicenter, parallel-group, 36-week study.
Results: A statistically significantly greater proportion of subjects in the alefacept plus nbUVB arm achieved the primary endpoint of PASI 75 at week 16 compared to subjects in the alefacept alone arm (44.9% vs 22.5%, P=0.032). Secondary outcomes were also in favor of the alefacept plus nbUVB group, including the proportion of subjects achieving a Physician Global Assessment (PGA) score of clear or almost clear at any time during the study (59.2% vs 34.7%, P=0.026) and reduction in percent body surface area (BSA) involved with psoriasis at week 16 (13.4% vs 8.0%, P<0.001). The onset of clinical response was significantly faster in the combination therapy group compared to monotherapy (mean time to PASI 75: 82 vs 107 days, P=0.007). Both treatments were generally well tolerated.
Limitations: Open-label, assessor-blinded study without a phototherapy-only treatment arm.
Conclusion: The addition of nbUVB to treatment with alefacept significantly enhanced and accelerated the clinical benefits of alefacept therapy and was generally safe and well-tolerated.

J Drugs Dermatol. 2012;11(8):929-937.

This supplement to the Journal of Drugs in Dermatology was made possible through an educational grant provided by Genentech, Inc.

BACKGROUND: The use of tumor necrosis factor inhibitors (TNFi) has been associated with a reduced incidence of type 2 diabetes mellitus.
OBJECTIVE: To compare changes in hemoglobin A1C and fasting glucose for patients exposed to TNFi.
METHODS: In this retrospective cohort study, patients with at least 3 recorded diagnosis codes for psoriasis, psoriatic arthritis, or rheumatoid arthritis between January 1, 2004 and July 31, 2011. Patients were Kaiser Permanente Southern California members for at least 1 year prior to the index date.
RESULTS: For hemoglobin A1C, there were 344 patients in the MTX cohort, and 118 patients in the TNFi+MTX cohort. In the covariate adjusted main effects ANCOVA model, the TNFi+MTX cohort had a lower mean change in hemoglobin A1C of -0.18mg/dL (95% CI: -0.35, -0.01) compared to the MTX cohort, although the difference is small and this model was not complete as there were significant interactions. For fasting glucose, there were 524 patients in the MTX cohort, and 121 patients in the TNFi+MTX cohort. In the covariate adjusted main effects ANCOVA model, change in fasting glucose was not significantly different between groups: -0.58 mg/dL (95% CI: -5.05, 3.88) for the TNFi+MTX cohort compared to the MTX cohort, although this model was not complete as there was a significant interaction.
CONCLUSIONS: The use of TNF inhibitors with MTX was not associated with a significant difference in the change of hemoglobin A1C or fasting glucose compared to MTX alone.

J Drugs Dermatol. 2015;14(2):159-166.

Infliximab was first approved by the FDA in 1998 as a treatment of moderately-to-severely active Crohn’s disease in patients who have an inadequate response to conventional therapies, and fistulizing Crohn’s disease. In November 1999 the FDA approved it for use in rheumatoid arthritis with methotrexate, and further expanded this indication in December 2000. It appears to be a promising agent in the treatment of a variety of inflammatory diseases, psoriasis in particular. A MEDLINE search was performed for “infliximab” in February of 2004, and the 1,116 articles found were reviewed. Approximately 200 articles were identified that contained references to the treatment with infliximab of skin disease, off-label uses, systemic diseases with cutaneous manifestations, and systemic and cutaneous side effects. These articles were reviewed and their contents summarized. Infliximab has been proven in well-controlled trial trials to ameliorate inflammatory bowel disease, rheumatoid arthritis, psoriasis, psoriatic arthritis, and ankylosing spondylitis. Anecdotal reports report it useful in treating the cutaneous manifestations and associations of inflammatory bowel disease, Behçet’s disease, graft versus host disease, Sjogren’s syndrome, refractory sarcoidosis, and a variety of other conditions. Its notable side effects include an increased risk of the induction of infections (e.g., tuberculosis). Infliximab is a very promising medication in the treatment of inflammatory dermatological conditions and should be used in larger scale trials of more diseases.

Adalimumab (HUMIRA™, Abbott Laboratories) is a new fully human TNF-? monoclonal antibody recently approved for the treatment of rheumatoid arthritis and undergoing trials for use in treating other conditions, including psoriasis and psoriatic arthritis. This article reviews its mechanisms of action, clinical trial results, and related discussion.

BACKGROUND: Acne and rosacea cause significant negative impact on quality of life. There is limited information comparing the health-related quality of life (HRQL) impact associated with acne and rosacea to other patient populations.
PURPOSE: We review available literature to assess the HRQL impact of acne and rosacea and compare them with major medical conditions.
METHODS: A PubMed search identified studies that utilized the Short Form 36 (SF-36), the Dermatology Life Quality Index (DLQI), and the willingness-to-pay (WTP) metric to assess the HRQL impact of acne and rosacea. These data were compared to HRQL values for other diseases.
RESULTS: The HRQL impact of acne is similar to asthma, epilepsy, diabetes, back pain, arthritis, and coronary heart disease using SF-36 data. DLQI scores for acne ranged from 2 to 17.7 and for rosacea ranged from 4.3 to 17.3; the DLQI scores for psoriasis ranged from 1.7 to 18.2. WTP data identified ranged widely for both acne and rosacea.
LIMITATIONS: There was limited broadly generalizable data for acne and rosacea.
CONCLUSIONS: Acne and rosacea impact HRQL to a similar degree as other major medical conditions by indirect comparison to psoriasis, a skin condition causing significant disability, and by direct comparison for acne. In the setting of limited health care resources, allocation should be grounded in the evidence that acne and rosacea are not trivial in their effects.

J Drugs Dermatol. 2014;13(6):692-697.

Introduction: Infliximab is indicated for severe plaque psoriasis (PsO). The investigators compared safety event rates in infliximab PsO trials with those of the general United States and PsO populations.
Methods: Integrated data (n=1373 patients) were compared with external databases.
Results: The analyses reported here are based on 1106 patient years and 116 patient years of follow-up in the infliximab group and the placebo group, respectively. The standardized mortality ratio in infliximab-treated patients (0.17 [95% confidence interval [CI]: 0.00-0.92], 1 patient died) was lower than that of the general PsO population. No death occurred in the placebo group. Comparing with the psoriasis population, the standardized incidence ratios (SIRs) for hospitalization were 1.16 (95%CI: 0.92-1.43) in infliximab-treated patients and 1.07 (95%CI: 0.46-2.11) in placebo-treated patients. For serious infection, the SIRs were 1.28 (95%CI: 0.78-1.97) in infliximab-treated patients and 1.47 (95% CI: 0.18-5.32) in placebo patients. The incidence of tuberculosis (TB) among infliximab-treated patients was 0.18 per 100 pa- tient-years (95% CI: 0.02-0.65). No TB occurred in the placebo group. Standardized incidence ratio for malignancy (excluding nonmelanoma skin cancers) was 0.39 (95% CI: 0.05-1.42; 2 malignancies) in infliximab-treated patients. No malignancy occurred in the placebo group.
Limitations: Exclusion criteria in clinical studies may bias selection of subjects who are healthier than the general population. Additionally, the limited number of patients followed over a maximum of 1 year can limit the ability to detect infrequent events or those events that require prolonged follow-up to detect. Nonmelanoma skin cancers were excluded from the analysis. Finally, populations and adverse event definitions may have differed in external databases and studies.
Conclusion: Based on the data from external databases, mortality, hospitalization, and serious infection rates in infliximab-treated patients were generally comparable to or less than that of the PsO population. Internal malignancy rates were similar to that expected in the general US population. However, the limitations of these data must be considered when compared with the totality of the safety profile of inflix- imab generated across all indications.

BACKGROUND: Psoriasis (Ps) is a chronic inflammatory immune-mediated skin disease that has been identified as a risk factor for various conditions including neoplasms. OBJECTIVE: To compare prevalence of cancer between Ps and Ps-free patients. METHODS: Adult patients continuously enrolled for ≥12 months (≥1 month in 2014) were selected from a large United States (US) claims database (Q1:2010–Q4:2014) and classified as Ps patients (≥2 Ps diagnoses; International Classification of Diseases 9th Revision, [ICD-9] code: 696.1x) and Ps-free patients (no Ps diagnosis). Patients were exactly matched (1:1) based on age, gender, state of residence, and insurance plan type. Prevalence of cancer was compared between cohorts over patients’ last 12 months of continuous healthcare plan enrollment using logistic-regression models. RESULTS: A total of 179,066 pairs of Ps and Ps-free patients were selected. Median age was 54.0 years, 51.7% were females. Prevalence of cancer was higher among Ps patients for any type of neoplasms (OR [95% confidence interval (CI)]=1.86 [1.83; 1.89]), malignant neoplasms (OR [95% CI]=1.53 [1.49;1.57]), as well as malignant skin neoplasms (OR [95% CI]=1.87 [1.79; 1.95]), lymphatic and hematopoietic tissues (OR [95% CI]=1.70 [1.57;1.84]), genital (OR [95% CI]=1.33 [1.26;1.41]), breast (OR [95% CI]=1.32 [1.24;1.40]), digestive organs and peritoneum (OR [95% CI]=1.24 [1.13;1.35]), urinary organs (OR [95% CI]=1.49 [1.36;1.64]), respiratory and intrathoracic organs (OR [95% CI]=1.30 [1.17;1.44]), and metastatic cancer (OR [95% CI]=1.14 [1.06;1.24]), all P less than 0.01. LIMITATIONS: Impact of Ps severity could not be assessed. CONCLUSION: Ps patients had a higher prevalence of cancer than Ps-free patients. J Drugs Dermatol. 2018;17(2):180-186.

The therapeutic paradigm in psoriasis includes antitumor necrosis alpha agents that have been proved effective and safe as long-term therapy. Recently, it has been described a correlation between the use of biologic agents and the occurrence of monoclonal gammopathies, which are haematological conditions characterized by clonal plasma cells proliferation producing a monoclonal immunoglobulin that accumulates in the blood.
OBJECTIVE: The aim of this study is to detect electrophoretic abnormalities in psoriatic patients undergoing treatment with infliximab.
RESEARCH DESIGN AND METHODS: A retrospective study evaluating all charts from the clinic database of all patients treated with infliximab. The evaluation of serum protein profile is routinely performed in the clinical setting during biologic therapies. We reported the occurrence MGUS in infliximab-treated patients.
RESULTS: The study analysis included 141 charts. Overall, 23 patients showed a MGUS in their electrophoretic profile, though in 6 cases MGUS was detected at the baseline. Thereby, 17 cases (12.06% of the study population) developed MGUS during infliximab therapy.
CONCLUSIONS: Serum protein electrophoresis test represents a useful tool to detect and monitor any potentially harmful condition that could occur during treatment with a biologic agent. Particularly, it could be crucial for the detection of MGUS, which does not affect clinical response, and it does not represent a criteria to withdraw the treatment.

J Drugs Dermatol. 2016;15(2):134-138.

Background: Ustekinumab, a fully human immunoglobulin (Ig) G1κ monoclonal antibody directed against the p40 subunit of interleukin (IL)-12/23, has demonstrated efficacy in patients with moderate-to-severe psoriasis. Objective: To evaluate the effect of IL-12/23 inhibition on immunocompetency by antigen-recall response in a preclinical multipledose toxicology study and three single-dose, phase 1 studies. Methods: Cynomolgus monkeys (Mauritius; n=32) treated with subcutaneous (s.c.) placebo or ustekinumab 22.5 or 45 mg/kg twice weekly for 26 weeks were assessed for antibody responsiveness to keyhole limpet hemocyanin (KLH). Patients with psoriasis or multiple sclerosis who received a single-dose of placebo (n=8) or ustekinumab (n=46) 0.09–4.5 mg/kg intravenous (i.v.) or 0.27–2.7 mg/kg s.c. were assessed by pneumococcal and tetanus antigen challenge. Primary T-cell response was not assessed in humans. Results: Anti-KLH antibody responses in ustekinumab-treated cynomolgus monkeys were comparable to those observed in placebotreated animals. A normal antibody response (≥two-fold increase from baseline) to pneumococcal antigen was seen in 34/46 (73.9%) ustekinumab-treated versus 4/8 (50%) placebo-treated patients. A normal antigen-recall response (≥four-fold increase from baseline) was seen in 12/20 (60%) ustekinumab- and 4/5 (80%) placebo-treated patients following tetanus toxoid exposure. Percentages of circulating immune cells were not affected by ustekinumab treatment. Conclusion: Results in nonhuman primates and human patients suggest that ustekinumab treatment does not significantly impair recall humoral immune system functions.

Over the last several years, a new generation of therapies for psoriasis has been in development. These biologic therapies target the activity of T lymphocytes and cytokines responsible for the inflammatory nature of this disease. In this review, we present an update on the progress of the four biologic agents in the forefront: infliximab, etanercept, efalizumab, and alefacept. The mechanism of each drug will be reviewed, as well as the most recent efficacy and safety data.

This activity is supported by an educational donation provided by Astellas Pharma US Inc. and Amgen and Wyeth Pharmaceuticals.

BACKGROUND: Topical corticosteroids are the most common dermatologic medications and are available in numerous different vehicles. Adherence is limited by traditional vehicles because they are messy and time consuming to apply. The preferred spray formulations have the advantage of being applied with ease, resulting in improved adherence and subsequently improved psoriasis. One limitation of topical treatments, especially spray vehicles, is the potential for irritation and sensitization.

OBJECTIVE: To evaluate the irritation and sensitization potential of topical desoximetasone spray formulation.

METHODS: A multicenter, double-blinded, randomized, controlled study assessed the irritancy and sensitization of 0.25% and 0.05% topical desoximetasone spray. Controls included vehicle, a positive control (0.1% sodium lauryl sulfate), negative control (0.9% saline), and an active comparator control (clobetasol spray). The primary outcome of the study was to evaluate the difference in mean cumulative irritation and potential sensitization response of desoximetasone 0.25% and 0.05% topical sprays.

RESULTS: Of the 297 enrolled, 269 completed the study per protocol for the irritation phase and 250 completed the protocol for the sensitization phase. At 22 days, desoximetasone 0.25 and 0.5% spray were less irritating than clobetasol 0.05% spray; mean irritation score difference of -0.46 and -0.57, respectively. Median total irritation score over the 22 days was 0 for all products. No subjects demonstrated any sensitization reaction to any of the six products. No serious adverse reactions were reported.

LIMITATIONS: Selection bias, use of a healthy population, limits the external validity. In addition, the duration of the study was short lived, unlike numerous inflammatory skin diseases. Conclusions: Desoximetasone spray has little potential for irritation or sensitization. The availability of another spray option for patients desiring less messy treatment may facilitate better adherence and treatment outcomes.

J Drugs Dermatol. 2017;16(8):755-758.

Mycophenolate mofetil is commonly used as a steroid-sparing agent effective in the management of erythema nodosum, idiopathic nodular panniculitis (Pfiefer-Weber-Christian disease), bullous pemphigoid, pemphigus vulgaris, and psoriasis. We report a case of nodular vasculitis responsive to mycophenolate mofetil. The clinical presentation, etiology, and management options for nodular vasculitis are discussed.

The use of Polypodium leucotomos, a species of fern, has been reported to be beneficial in the treatment of atopic dermatitis, vitiligo, and psoriasis, and for prevention of polymorphic light eruption, sunburn, and squamous cell carcinoma. We review the in vivo animal, in vitro human, and human clinical studies performed to help elucidate the actions of and biologic pathways affected by P. leucotomos. These results serve as the scientific rationale and basis for the protection and effectiveness afforded by P. leucotomos in cutaneous diseases.

J Drugs Dermatol. 2016;15(2):224-228.

Background: The results of long-term studies on the efficacy and safety profiles of the biologics for patients with psoriasis are starting to appear in the literature. Not only are the results promising for the biologics as a whole, but the high number of patients remaining in these clinical trials after extended periods of time, or retention, may also reflect additional benefits of these biologics. The aim of this review was to manuscript aims to compare rates of attrition for the various biologic therapies in pivotal clinical trials in order to assess and compare adherence of patients to long-term use of the different biologic agents, also known as biologic survival.
Methods: An in-depth literature review was conducted using PubMed and MEDLINE. Randomized, controlled trials utilizing biologic agents as monotherapy for the treatment of psoriasis were analyzed for patient numbers over time. Studies which provided data on patient retention for at least 24 weeks were selected, graphed, and compared. Reasons for discontinuation were noted.
Results: Nineteen trials were selected, graphed and charted to compare attrition rates of the various biologic therapies. Due to differences in sample size, study design, dosing regimens, study duration and limited data with regards to patient numbers, it is difficult to reach a definitive conclusion as to which biologic agent is associated with the lowest rate of discontinuation. However, given the data available, etanercept appears to be the most successful therapy in terms of patient retention in studies both greater than and less than 30 weeks. For the studies using various dosing regimens, intrastudy attrition rates are also compared.
Conclusion: While the data available thus far on patient retention for the biologic therapies are very limited, preliminary conclusions can be drawn. Among the available biologic agents, etanercept appears to be associated with the lowest rate of discontinuation. This may be due to greater superior effiacy and to a decreased likelihood of experiencing adverse events.

BACKGROUND: Valrubicin is a semisynthetic anthracycline developed as an anti-cancer drug able to ameliorate psoriasis and non-melanoma skin cancer (NMSC) by topical application in animal models. Valrubicin decreases cell proliferation, and induces apoptosis; however its mode of action is still unknown. Valrubicin localizes in the cytoplasm and its valerate moiety resembles diacylglycerol, an activator of protein kinase C (PKC) α, which belongs to the PKC family of cytoplasmic serine/threonine protein kinases. PKCα is observed in the suprabasal layers of normal skin and is associated to keratinocyte growth arrest and differentiation processes. In hyper-proliferative skin diseases the presence of PKCα is altered.
OBJECTIVE: The aim of the present study was to investigate valrubicin’s mode of action in keratinocytes by studying its possible effect on PKCα activation.
METHODS: PKCα's characteristic to translocate from the cytoplasm to the cellular membrane when activated was assessed by measuring the amount of PKCα in the soluble and membrane-bound protein fractions isolated from valrubicin stimulated keratinocytes and by visualizing PKCα in stimulated cells over time. Downstream signaling was investigated by measuring the amount of phosphorylated Myristoylated Alanine-rich C-kinase substrate (MARCKS) and extracellular signal-regulated kinases (ERK) 1/2 of valrubicin-stimulated keratinocytes. To investigate whether there was a direct interaction between valrubicin and PKCα, an activity assay employing purified PKCα protein was used.
RESULTS: Valrubicin activates PKCα in vitro as shown by PKCα's translocation and phosphorylation of downstream signaling molecules.
CONCLUSION: Valrubicin stimulates PKCα activity and downstream signaling which may contribute to its beneficial effect in psoriasis and NMSC.

J Drugs Dermatol. 2013;12(10):1156-1162.

Desensitization is the process of rendering an individual who is allergic to a food or chemical substance like a drug able to tolerate the agent. This is usually accomplished by exposing the patient to incrementally increasing doses, injecting the offending agent over periods of time as is done in situations of grass or tree pollen allergy. In the current case report we demonstrate the first method to desensitize a patient to the anti-TNF medicament etanercept using immune suppressants rather than the older technique of incrementally increasing injection doses.

J Drugs Dermatol. 2013;12(10):1168-1169.

Cytokines are polypeptides that are produced by various cell types and act in an autocrine or paracrine manner. They have many different biological actions and have been used in dermatology to treat a wide range of dermatologic diseases. In this paper we review some of the more commonly used cytokines in dermatology, including interferon-alpha and -gamma, interleukins- 2 and -10, and granulocyte-macrophage colony-stimulating factor. We specifically examine their roles in the treatment of condyloma and verruca, hemangiomas, keloids, skin cancers, atopic dermatitis, psoriasis, Behçet disease, chronic granulomatous disease, wound healing, and cutaneous T cell lymphoma. In addition, some of the adverse effects associated with these cytokines are discussed.

Phototherapy is often used to treat inflammatory skin conditions such as psoriasis and eczema. Much progress has recently been made in understanding the mechanisms underlying the local, cutaneous immune effects induced by phototherapy. Unlike many immunosuppressive drugs used in the management of inflammatory skin disease, phototherapy not only targets effector immune cells but also appears to up-regulate regulatory T cells (Tregs). Additionally, phototherapy reverses epidermal barrier abnormalities common in these diseases, allowing for restoration of cutaneous homeostasis.

J Drugs Dermatol. 2014;13(5):564-568.

The long-established notion that rosacea is worsened by light is of particular concern in the phototherapy of diseases such as psoriasis, eczema, or vitiligo, which often can be coexistent with rosacea. A literature search was conducted and much evidence was found to challenge this belief that light adversely affects rosacea. In fact, more patients actually improved with sunlight in a more recent published survey. Several other studies have also shown that rosacea patients were similar to control subjects in sun exposure, solar skin damage, and sun sensitivity. Additionally, all clinical trials to date have failed to find a difference between rosacea patients and control subjects when challenged with ultraviolet light. Thus, phototherapy with rosacea may be safer than is commonly believed.

Background: Some dermatologic disorders are known to be much more common in patients of color, but the leading dermatologic disorders in patients of color have not yet been described on the basis of nationally representative data.
Purpose: To determine the leading dermatologic disorders for each major racial and ethnic group in the United States.
Methods: We queried the National Ambulatory Medical Care Survey (NAMCS) for the leading diagnoses in patient visits to U.S. dermatologists from 1993 to 2009. The leading diagnoses were tabulated for each racial and ethnic group, and the top conditions were compared between groups. In a separate analysis, visits for skin conditions regardless of physician specialty were analyzed for leading diagnoses in each racial and ethnic group.
Results: The top five diagnoses for African-American patients in dermatology clinics were acne, unspecified dermatitis or eczema, seborrheic dermatitis, atopic dermatitis, and dyschromia. For Asian or Pacific Islander patients, the top five were acne, unspecified dermatitis or eczema, benign neoplasm of skin, psoriasis, and seborrheic keratosis. By contrast, in Caucasian patients, the top five were actinic keratosis, acne, benign neoplasm of skin, unspecified dermatitis or eczema, and nonmelanoma skin cancer. In Hispanic patients of any race, the leading diagnoses were acne, unspecified dermatitis or eczema, psoriasis, benign neoplasm of skin, and viral warts. When the leading dermatologic diagnoses across all physician specialties were assessed, the top diagnoses for African-Americans were unspecified dermatitis or eczema, acne, dermatophytosis of scalp and beard, sebaceous cyst, and cellulitis or abscess; for Asians or Pacific Islanders were unspecified dermatitis or eczema, acne, atopic dermatitis, urticaria, and psoriasis; and for Caucasians were acne, unspecified dermatitis or eczema, actinic keratosis, viral warts, and sebaceous cyst. For Hispanics of any race, they were unspecified dermatitis or eczema, acne, sebaceous cyst, viral warts, and cellulitis or abscess. For a sole diagnosis of a dermatologic condition, only 28.5% of African-Americans' visits and 23.9% of Hispanics' visits were to dermatologists, as compared to 36.7% for Asians and Pacific Islanders and 43.2% for Caucasians.
Limitations: The data are based on numbers of ambulatory care visits rather than numbers of patients. Data on race or ethnicity were not collected for some patients.
Conclusions: Several dermatologic disorders are much more commonly seen in patients of color. Acne and unspecified dermatitis or eczema are in the top five for all major U.S. racial and ethnic groups. There may be an opportunity to improve the care of patients of color by ensuring they have equal access to dermatologists.

J Drugs Dermatol. 2012;11(4):466-473.

BACKGROUND: Injection-site reactions (ISRs) are reported with biologic therapies. The objective of this study was to comprehensively characterize ISRs among moderate-to-severe psoriasis patients treated with ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A.

METHODS: ISRs are presented from UNCOVER-1, UNCOVER-2, and UNCOVER-3 (12 weeks) and all ixekizumab-exposed patients in 11 controlled and uncontrolled trials (156 weeks).

RESULTS: At week 12, reported ISR frequency with 80 mg ixekizumab every 2 weeks (IXE Q2W, 16.8%) was comparable with etanercept twice weekly (16.4%); both were significantly higher than placebo (3.3%). With IXE Q2W, ISRs were mild (12.3%), moderate (3.9%), or severe (0.7%), typically reported in the first 2 weeks (median onset, 6.6 days), and most commonly characterized as nonspecified, erythema, and pain. Generally, erythema onset was delayed, whereas pain occurred around drug administration. Discontinuation from ixekizumab due to ISRs (0.4%) occurred in the first 12 weeks. After 2 weeks, ISR frequency decreased and remained stable (≤4.2%) through week 156. No ISR-related serious adverse events were reported in ixekizumab-treated patients. ISR data were solicited if patients reported injection-associated events. Since nonspecified ISR was the most commonly reported term, specific types might be underreported.

CONCLUSIONS: ISRs have been reported with ixekizumab during clinical trials. These reactions are typically tolerable, manageable, and decrease over time.

Clinicaltrials.gov: NCT01474512 (UNCOVER-1); NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3); NCT01777191 (UNCOVER-A); NCT01624233 (UNCOVER-J); NCT01107457 (I1F-MC-RHAJ); NCT02561806 (I1F-MC-RHBS); NCT02387801 (I1F-US-RHBO);NCT02513550 (I1F-MC-RHBP); NCT02634801 (I1F-EW-RHBZ)

J Drugs Dermatol. 2018;17(2):200-206.

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Allergan's Tazorac is at the Vanguard of the Next Generation of Topical Retinoids

Over the last 4 decades, topical retinoids have become standard therapy for the treatment of acne vulgaris. Although the market currently encompasses multiple formulations of next-generation topical retinoids, Tazorac is unique among them due to its dual role as a treatment option for both acne vulgaris and psoriasis vulgaris. Tazorac has also demonstrated that it is highly effective for the treatment of acne vulgaris as a monotherapy or in combination with other agents. Recent studies show that Tazorac can be combined effectively with dapsone 5% gel or with a benzoyl-peroxide - containing formulation to augment efficacy. Additionally, Tazorac does not have a generic substitution, so physicians can be assured that their patients will receive exactly what they have been prescribed.

Alopecia, hypertrichosis, and hirsutism may be caused by a variety of medications. Drug-induced alterations in the texture or structure of the hair shaft, however, are much less common. We report a female patient who presented with acquired generalized kinking of the hair 6 months after the initiation of acitretin therapy for psoriasis. The hair change has persisted despite reductions in the dose of acitretin. To our knowledge, this is the first report of hair kinking induced by acitretin. It has been proposed that retinoid therapy may affect keratinization of the inner root sheath to cause this structural hair shaft change.

Trachyonychia is the term used to describe nail plate roughness, pitting, and ridging that may affect 1 to 20 nails. Alopecia areata, psoriasis, lichen planus, atopic dermatitis, ichthyosis vulgaris, as well as other skin conditions have been associated with trachyonychia, but the causal relationship is often challenging to demonstrate histologically. Clinical evidence of these cutaneous disorders in conjunction with a nail matrix biopsy may help elucidate an etiology of trachyonychia, but many cases often remain idiopathic. Nail biopsy findings may match skin histology, but more commonly show spongiotic or nonspecific changes. We present an interesting case of a female with progressive development of trachyonychia in all 20 nails coinciding with a new diagnosis of sarcoidosis.

Biologic drugs, a novel class of agents engineered to target specifc mediators of infammation, and small-molecule inhibitors that pen-etrate the cell membrane to interact with targets inside a cell represent the cutting-edge of pharmacological biomedical therapeutics. Clinical studies have already demonstrated the effectiveness of this new generation of drugs in treating a variety of medical illnesses and conditions that were refractory to traditional treatments. This review aims to describe the latest available or currently in-develop-ment drugs, biologic agents, and small molecule inhibitors for treatment of psoriasis, rosacea, alopecia areata, and atopic dermatitis.

J Drugs Dermatol. 2017;16(12):1224-1228

Oral lichen planus is a very difficult condition to treat and causes patients to experience pain and difficulty eating. Therapeutic approaches focus on minimizing flares and relieving pain and discomfort to improve patient quality of life. Topical preparations are the mainstay of therapy, but they are often insufficiently efficacious for more severe cases. The use of systemic agents can be complicated by potentially serious adverse effects, the need for regular monitoring, suboptimal efficacy, and cost. Reported here are 3 recalcitrant cases of oral lichen planus that were effectively treated with apremilast, a drug recently approved for psoriasis and psoriatic arthritis.

J Drugs Dermatol. 2016;15(8):1026-1028.

Polypodium leucotomos extract (PLE), derived from the tropical fern of Polypodiaceae family, has properties ranging from immunomodulatory and antioxidative to photoprotective. It is these multiple mechanisms of action, in combination with a favorable side effect profile, which makes PLE a promising adjunctive treatment for several dermatologic disorders. Studies are summarized on the use and potential applications of PLE in the treatment or management of photodermatoses, vitiligo, melasma, psoriasis, atopic dermatitis, and more recently, in minimizing infections in high-performance athletes. More data, however, with larger sample sizes are needed to confirm these benefits.

J Drugs Dermatol. 2014;13(2):148-153.

Background: The longstanding concept of a Th1-Th2 dichotomy in leprosy, with Th1-predominant tuberculoid leprosy and Th2-predominant lepromatous leprosy (LL), has recently been challenged, and Cbl-b overexpression may emerge as an important factor in anergy and progression of LL. Moreover, Th17 and Th22 subsets have been identified as Th1-Th2 modulators in inflammatory skin diseases, most notably psoriasis, but their roles in leprosy have not yet been elucidated. The occurrence of pseudoepitheliomatous hyperplasia (PEH) with transepidermal elimination of mycobacteria in LL patients, which could theoretically be a portal for contact transmission, thus raises important immunological questions: Do Th17 and/or Th22 subsets mediate epidermal proliferation akin to Th1-driven psoriasis in supposedly Th2-predominant LL disease, and is the Th1-Th2 immunostat set systemically or locally? Furthermore, which microRNAs (miRs), signal transducers, and activators of transcription (STAT) proteins regulate this transition in leprosy, if any, and does differential Cb1-b expression play a role?
Observation: A 71-year-old man presented with an infiltrative dermopathy characteristic of LL, as well as several hyperkeratotic plaques. Microscopic examination of the hyperkeratotic lesions demonstrated PEH with loss of the grenz zone and transepidermal elimination of acid-fast bacilli, whereas classic histopathologic features of LL were present at other sites.
Hypotheses: We hypothesize that: Th17 and Th22 T-cell subsets act locally to induce T-cell plasticity in LL lesions, manifesting PEH; miR-181a is normal or increased in LL lesions with PEH compared to its expressional loss in classic LL lesions; miR-21 and STAT3 are increased in LL lesions with PEH, given their association with epithelial hyperproliferation; and Cbl-b is diminished in LL lesions with PEH compared to classic LL lesions.
Conclusion: By understanding the factors that regulate T-cell and cytokine responses in leprosy, it should be possible to recognize these dynamic immunologic processes clinically and histopathologically and devise specific immunologic interventions.

J Drugs Dermatol. 2012;11(10):1233-1235.

Topical retinoids are an important class of drugs for treating several dermatoses occurring more frequently in patients with pigmented skin, such as melasma, post-inflammatory hyperpigmentation, pseudofolliculits barbae and keloids. They also play a role in managing acne, psoriasis, photoaging, cutaneous T-cell lymphoma, Kaposi sarcoma and disorder of hyperkeratosis in this demographic as well. In general, topical retinoids are well tolerated in pigmented skins. There is little evidence to suggest that patients with darker skin are at increased risk of irritation. However, retinoid dermatitis can induce post-inflammatory hyperpigmentation and attempts should be made to reduce its occurrence by modifying treatment regimens in patients with pigmented skins.

J Drugs Dermatol. 2011;10(5):483-489.

This second part of a 2-part review on the use of biologics for treatment of patients with psoriasis is focused on currently approved therapies that work through modulation of T cells: alefacept, a leukocyte function - associated antigen 3-immunoglobulin G fusion molecule; and efalizumab, an anti-CD11 humanized antibody. Efficacy and safety data from pivotal clinical trials are summarized and new data are presented for these biological agents, and considerations for optimal therapeutic selection are discussed. Clinical data from investigational agents currently in development are also reviewed. One of these new agents is ustekinumab, a humanized antibody that targets interleukins 12 and 23 and inhibits the differentiation of Th17 cells, a recently identified subset of CD4+ T-helper cells.

Pityriasis rubra pilaris has no single effective therapy and there are some cases resistant to multiple treatments. Psoriasis has clinical and therapeutic response overlaps with pityriasis rubra pilaris and there are several therapies common to both, such as retinoids, methotrexate, cyclosporine A, phototherapy, and most recently infliximab. We report a case of a 10-year-old boy with pityriasis rubra pilaris unresponsive to topical corticosteroids, salicylic acid, pimecrolimus, calcitriol, calcipotriol, ultraviolet B targeted phototherapy, isotretinoin, systemic PUVA, acitretin, and etanercept. He was treated with efalizumab 1 mg/kg weekly and a successful outcome was obtained with a 50% improvement after the first dose. The patient remains in remission after 9 months of treatment.

Diaper dermatitis is the most common dermatologic disorder of infancy. Its cause can often be determined clinically based on the clinical presentation. Primary diaper dermatitis is associated with irritants and spares the deep skin folds. Secondary diaper dermatitis is most often caused by Candida yeast overgrowth and typically presents as a well-defined area of beefy red erythema covering the diaper area and including the deep folds of skin with hallmark satellite pustules. Other causes include seborrheic dermatitis, psoriasis, acrodermatitis enteropathica, allergic contact dermatitis, Langerhans cell histiocytosis, and, in the setting of a primarily pustular eruption, bacterial folliculitis. A simple potassium hydroxide preparation (KOH) can confirm the diagnosis of candida diaper dermatitis and guide proper treatment.

Elephantiasis nostras verrucosa is a rare disorder characterized by dermal fibrosis, hyperkeratotic, verrucous, and papillomatous le- sions that result from both chronic filarial and nonfilarial lymphedema. Various treatment options have been reported for this disease. We present a 64-year-old man with erythrodermic psoriasis and elephantiasis nostras verrucosa in whom the lesions were resolved almost completely after acitretin treatment.

J Drugs Dermatol. 2012;11(3):402-405.

The author presents the case of a 27-year-old man who suffered 2 episodes of erythroderma while on therapy with efalizumab for psoriasis. The fi rst episode, occurred 2 weeks after the fi rst dose, was well controlled without discontinuing the drug. A second eryth- rodermic fl are was observed after 4 weeks following efalizumab reintroduction. In this case, oral methotrexate was administered as monotherapy during 4 months, and then was tapered off and efalizumab again reintroduced for continuous treatment for a period 14 months with excellent results. This second episode of erythroderma was clinically accompanied by a marked hyperkeratosis, blepharitis, and nasal infection due to Staphylococcus aureus. Lymphocytosis and leukocyturia with negative urine culture were also reported in both episodes. As a result, it was concluded that the erythroderma was an adverse reaction to efalizumab that could be solved without treatment discontinuation. The author considered this patient as a good responder to continuous treatment with efalizumab.

Topical corticosteroids have improved the management of many inflammatory skin diseases, such as psoriasis and atopic dermatitis. However, these medications are associated with certain adverse effects that are potentially serious. The potent anti-inflammatory actions of these drugs increase susceptibility to bacterial and fungal infections, and therefore may preclude them from use when infection is the known cause of the disease. In addition, children may be more vulnerable than adults to systemic effects of topical corticosteroids because percutaneous absorption is proportionately greater. These are important considerations, and physicians need to weigh and compare the risks and benefits associated with these medications before initiating treatment. This involves an appreciation of which patient populations are at high risk, which skin conditions are incompatible with topical corticosteroid therapy, and which alternative nonsteroidal medications are effective in treating inflammatory skin diseases.

Atopic dermatitis has been characterized as an autoimmune or auto-allergic phenomenon in which environmental allergens resembling human proteins activate auto-reactive T-cells to release pro-inflammatory cytokines of the T-helper 2 (Th2) cytokine profile (IL-4, IL-5, IL-10, and IL-13)1-3. Infliximab is a chimeric IgG1 monoclonal antibody that blocks the effects of the inflammatory cytokine tumor necrosis factor (TNF)-?. Infliximab has been shown to benefit greatly patients suffering from diseases associated with a Th1 profile (IL-1, TNF-?, and IFN-?), such as psoriasis, Crohn’s disease and rheumatoid arthritis4-8. Some researchers have suggested that disrupting the Th1-Th2 balance by downregulating Th1 cytokines may result in manifestations of Th2 disease. Consistent with this hypothesis, we present the cases of three patients who exhibited vivid manifestations of atopic dermatitis after the inception of infliximab induction therapy.

Anti-tumor necrosis factor-α (TNF-α) immunotherapy is revolutionizing the treatment of immune disease, particularly Crohn’s disease, rheumatoid arthritis, psoriatic arthritis and psoriasis. The role of anti-TNF-α agents in the management of cutaneous lupus erythematosus (LE), however, is not as clear. While experimental reports have suggested a potential benefit of anti-TNF-α therapy in severe cutaneous LE, newer reports have identified these medications as instigators or exacerbators of the disease. In this review, the authors present a case of a patient whose persistent discoid LE (DLE) was exacerbated by a trial of adalimumab, one of the currently available TNF-α-blocking agents. The authors review 128 cases in the literature in which anti-TNF-α therapy was implicated in cutaneous LE pathogenesis, with emphasis on DLE, and consider a number of mechanisms whereby this arguably paradoxical effect may occur. The authors then propose possible approaches to the management of anti-TNF-α therapy-induced cutaneous LE.

The Experience Diagnosing, Understanding Care, and Treatment with Enbrel® (EDUCATE) trial is a phase IV, 24-week, multicenter, open-label study of etanercept 50 mg weekly in the treatment of psoriatic arthritis (PsA) in community dermatology clinics. In this study, patients with active PsA and moderate to severe plaque psoriasis have measurable uses of healthcare resources at baseline, reflecting a burden of illness. Etanercept significantly reduced healthcare resource utilization, absenteeism, and caregiver assistance in PsA patients after 24 weeks of treatment. These results could translate into savings on both direct and indirect costs and improvements in health-related quality of life for patients with PsA.

Hand dermatitis is estimated to affect greater than 15% of the general population. Childhood eczema, frequent hand washing, and occupational exposure to chemicals are predisposing factors. Hand dermatitis treatment involves both prevention of outbreaks and treatment of active disease. Moisturizers are essential to protect the skin from the environment, enhance hydration, and repair the skin barrier. They have been shown in large studies to prevent occupational related breakouts. Natural oils are commonly used in moisturizers for their moisturizing and emollient properties. Sweet almond oil is an oil that contains high levels of fatty acids and has been used for centuries to treat skin diseases such as eczema and psoriasis. In this study, a moisturizer with 7% sweet almond oil and 2% colloidal oatmeal was found to be both safe and effective in treating patients with moderate to severe hand dermatitis.

J Drugs Dermatol. 2018;17(1):78-82.

Objective: Study results evaluating the efficacy and safety of clocortolone pivalate 0.1% cream in the treatment of adults, young children, and infants with inflammatory facial dermatoses are reported in this article. Clocortolone pivalate 0.1% cream, indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, is a mid-potency topical corticosteroid (Class 4) that has been studied and used extensively to treat a variety of corticosteroid-responsive inflammatory dermatoses, many of which often involve facial skin in both adults and children.
Methods: Clocortolone pivalate 0.01% cream was applied to affected facial skin in subjects presenting with seborrheic dermatitis, contact dermatitis, atopic dermatitis, or psoriasis. Application was completed three times daily for 21 days. Assessments of erythema, edema, transudation, lichenification, scaling, pruritus and/or pain were completed at baseline and Days 4, 7, 14, and 21. Overall therapeutic response was assessed at all follow-up visits. Forty-nine subjects were entered, ranging in age from 1 month to 88 years of age. Thirty-eight subjects completed the studies, with 11 subjects lost to follow-up after the first visit. Individuals between the ages of 13 and 19 years were pre-emptively excluded to avoid potential application of a corticosteroid to acne-affected or acne-prone skin.
Results: Treatment with clocortolone pivalate 0.1% cream resulted in decreases in erythema, edema, transudation, lichenification, scaling, and pruritus/pain in 76% of treated study subjects. The overall therapeutic response in approximately two-thirds of the subjects (68%) was rated as good to excellent. There were 7 adverse events noted over the course of the study that were judged to be related to treatment, all of which were cutaneous and localized to the site of application (acneiform eruptions, burning, and folliculitis).
Conclusion: Clocortolone pivalate 0.1% cream was effective in relieving the signs and symptoms of corticosteroid-responsive inflammatory dermatoses involving facial skin, including seborrheic dermatitis, contact dermatitis, atopic dermatitis, and psoriasis. Overall, the safety profile was favorable and devoid of any treatment-related serious adverse events.

J Drugs Dermatol. 2012;11(10):1194-1198.

Natural ingredients have been used traditionally for millennia and their application in topical creams, lotions and preparations within the traditional medicines and healing traditions of many cultures has been observed. Over the last 20 years, clinical and laboratory studies have identified the benefits of an array of natural ingredients for skin care. Consequently, a number of these ingredients and compounds are today being developed, used or considered not only for anti-aging effects, but also for use in dermatologic disorders. Certain ingredients, such as colloidal oatmeal and aloe vera, have been identified as beneficial in the treatment of psoriasis and atopic dermatitis, respectively, due to their anti-inflammatory properties. For combating acne and rosacea, green tea, niacinamide and feverfew are considered efficacious. As to hyperpigmentation and antioxidative capabilities, licorice, green tea, arbutin, soy, acai berry, turmeric and pomegranate are among those plants and compounds found to be most beneficial. Additional research is needed to determine to confirm and elucidate the benefits of these ingredients in the prevention and management of skin disease.

Dermatologists frequently employ combination therapy to treat various diseases, but the evidence to support the use of such combinations is often lacking. Synergy is an appealing although somewhat ambiguous concept in medicine. Utilizing synergy allows clinicians to provide the most efficacious combination of treatments to patients, while potentially minimizing adverse effects and reducing the development of drug resistance. Definitions of synergy vary, but ultimately converge on finding a therapeutic advantage in combining treatments. Here we discuss the concept of ‘therapeutic synergy’, which can be defined as an increase in the efficacy of a combination of treatments in comparison to any of its individual parts alone. We review the concept of therapeutic synergy in dermatology by discussing some of the evidence regarding combination therapies utilized in the management of atopic dermatitis, acne vulgaris, psoriasis, and cutaneous lupus erythematosus. Further meaningful investigation of therapeutic synergy and its applications in dermatology should be undertaken.

J Drugs Dermatol. 2016;15(10):1203-1207.

Colloidal oatmeal has a long history of beneficial use in dermatology. It is a natural product that has an excellent safety record and has demonstrated efficacy for the treatment of atopic dermatitis, psoriasis, drug-induced rash and other conditions. In recent years, in vitro and in vivo studies have begun to elucidate the multiple mechanisms of action of naturally derived colloidal oatmeal. Evidence now describes its molecular mechanisms of anti-inflammatory and antihistaminic activity. The avenanthramides, a recently described component of whole oat grain, are responsible for many of these effects. Studies have demonstrated that avenanthramides can inhibit the activity of nuclear factor κB and the release of proinflammatory cytokines and histamine, well known key mechanisms in the pathophysiology of inflammatory dermatoses. Topical formulations of natural colloidal oatmeal should be considered an important component of therapy for atopic dermatitis and other conditions and may allow for reduced use of corticosteroids and calcineurin inhibitors.

The dermatologic application of natural ingredients in skin care has evolved significantly in the past two decades. Research into the mechanisms and biochemistry of natural ingredients has lead to the development of new technologies and formulations that provide a therapeutic benefit in the treatment of dermatologic conditions and the aging process.
Providing optimal patient outcomes continues to be a challenge in the treatment and management of dermatologic conditions. Most physicians and patients are interested in doing everything possible to optimize the treatment of their skin disease. This is especially important in treating patients with chronic disorders such as eczema, acne, psoriasis, rosacea, photodamage and the negative effects of aging. Physicians and patients often explore the therapeutic benefits of natural ingredients as alternative or complementary treatments to conventional methods. It is important that dermatologists remain up-to-date on the research and new advances in skin care products with natural ingredients.

This is a CME supplement; visit the JDD Medical Education Library to participate in this activity and earn 1 category 1 CME Credit.

Background: Vitiligo is a common acquired pigmentary disorder with a profound psychosocial impact. The exact pathogenesis of vitiligo is not fully understood; however, vitiligo appears to be an autoimmune disease involving T-cell-mediated melanocyte destruction. Recently, complete clearance of coexisting vitiligo without recurrence over 2 years was reported in 2 psoriasis patients treated with alefacept.
Objective: To evaluate the safety and efficacy of alefacept in the treatment of vitiligo.
Methods: After providing informed written consent, 4 adult patients with widespread vitiligo (covering a body surface area ≥5%) were treated with weekly intramuscular injections of 15 mg alefacept for 12 weeks. All patients were monitored clinically, by laboratory investigation, and by digital image analysis. All patients were followed up with for 24 weeks.
Results: All patients tolerated alefacept well, without any adverse events. None of the patients showed any repigmentation. However, 1 patient developed new depigmented patches during treatment with alefacept.
Limitations: A pilot study with a small number of patients.
Conclusion: Alefacept as a monotherapy for vitiligo treatment did not result in any patient improvement, and further evaluation in larger studies may be required.

J Drugs Dermatol. 2013;12(2):159-161.

Tumor necrosis factor (TNF)-α is one of the oldest known cytokines in human physiology. It is involved in both normal and pathologic states. Virtually every cell and organ in the body are affected by TNF-α.¹ Though TNF-α is usually involved in inflammation as a normal host defense response, when overproduced, it can become pathologic and affect almost every organ system. In this article, we address the role of TNF-α in diseases such as rheumatoid arthritis, Crohn's disease, psoriasis, and ankylosing spondylitis as well as the drugs used to modulate TNF-α. Specifically, we look at the structure, mechanism of action, and clinical use for etanercept, infliximab, and adalimumab. Historically, we also review the drug lenercept, another TNF-α modulator. These drugs offer alternative effective treatments to rheumatologic and dermatologic diseases without as many of the toxic side effects of some of the traditional therapies. The traditional agents target TNF-α in addition to several other modes of action (disease modifying anti-rheumatic drugs [DMARDS] such as cyclosporine and methotrexate) (Table 1).

Though TNF-α immunomodulation seems to be a very effective, promising treatment in several TNF-α mediated disease processes, long-term studies need to be performed to assess the risk-benefit ratio of using these drugs over an extended period of time.

BACKGROUND: Biologics have transformed the treatment of psoriasis and psoriatic arthritis, but at a significant cost to payers and patients. The introduction of biosimilars into the US market could reduce costs while increasing access to biologic medications.

OBJECTIVE: We sought to identify gaps in biosimilar knowledge and perception among US dermatologists.

METHODS: An online survey was sent to dermatologists from January to April 2015.

RESULTS: Ninety-seven US dermatologists responded, of which 84% state they prescribe biologics in their practice. Only 37% of dermatologists were aware that a biosimilar is highly similar to a US-licensed reference biological product, 26% incorrectly described a biosimilar as a “generic” of a known biologic, and 10% of dermatologists stated they did not know the definition. Most dermatologists (88%) believe that substitutions from biologics to biosimilars will be made by pharmacists without consulting the physician. A total of 37% of dermatologists believed that a biosimilar with the same name as a biologic suggested they are “structurally identical.” Only 25% said they would likely prescribe biosimilars to their patients, while 38% stated they would try using them on a very select, small group of patients before trying it on a majority of their patients.

LIMITATIONS: Limitations include small sample size and non-responder bias.

CONCLUSION: A biosimilars knowledge gap exists amongst dermatologists, suggesting the need for more educational initiatives.

J Drugs Dermatol. 2017;16(6):612-615.

CD70 (CD27L) has been shown to be preferentially expressed on Th1, but not Th2, CD4+ lymphocytes in murine contact sensitivity. The CD70-CD27 co-stimulatory pathway as well as the Th17 subset of lymphocytes have also been identified in human contact sensitivity reactions. The authors have previously reported increased expression of CD70 and the Th17-specific transcription factor retinoid orphan receptor gamma T in the elicitation phase of allergic contact dermatitis by reverse transcriptase-polymerase chain reaction. The manipulation of these pathways has potential for ameliorating autoimmune and inflammatory disorders such as allergic contact dermatitis, psoriasis and rheumatoid arthritis. Also, upregulation of the CD70-CD27 and Th17 pathways has been associated with the remarkable ability of topical sensitizers to treat warts and skin cancers including melanoma. As natural killer and natural killer T cells are also involved in contact sensitivity, future studies investigating the function of these cells are necessary to elucidate the transition between innate and acquired immune responses in the context of the Th1/Th2/Th17 and regulatory T cell paradigm.

J Drugs Dermatol. 2011;10(10):1192-1194.

BACKGROUND: Topical corticosteroids are the standard-of-care treatment for dermatitis, mild psoriasis, and other inflammatory skin diseases. Prescribing practices rely on knowledge of topical corticosteroid potency, as well as potential side effects including steroid allergies.
PURPOSE: The primary aim of this study is to determine how dermatologists classify particular topical corticosteroids according to potency, and which products they prefer in cases when allergenicity is a concern.
METHODS: The data were collected and analyzed from 105 US-based dermatologists surveyed at the 2011 Summer American Academy of Dermatology meeting.
RESULTS: The majority of dermatologists were in agreement on the potency ranking of many commonly prescribed topical corticosteroids. Two thirds of the surveyed dermatologists expressed concern about allergy to topical corticosteroids. In cases of a suspected allergy, desoximetasone was the leading product dermatologists would choose to prescribe.
LIMITATIONS: The survey was limited to attendees of an educational conference, possibly leading to an overestimation of dermatologist knowledge of topical steroids.
CONCLUSIONS: This study shows that dermatologists are generally knowledgeable about group classifications of corticosteroids in terms of potency and that they can appropriately select a topical product with low potential for allergy.

J Drugs Dermatol. 2013;12(7):786-789.

Cutaneous reactions to imatinib are common and occur in 9.5% to 69% of patients depending on the series reported. Maculopapular eruptions, erythematous eruptions, edema, and periorbital edema are the most common adverse events observed. Imatinib can also induce severe skin eruptions and generalized skin eruptions. Toxic epidermal necrolysis and Stevens Johnson syndrome has been linked to the use of imatinib. Imatinib has caused acute generalized exanthematous pustulosis. Purpuric vasculitis and mycosis fungoides-like reactions has occurred after imatinib use. Rarer side effects include: hypopigmentation, lichenoid reactions, pityriasiform eruptions, pityriasis rosea, psoriasis, reactivation or induction of porphyria cutanea tarda, neutrophilic eccrine hidradenitis, Sweet’s syndrome, erythema nodosum, EBV-positive cutaneous B-cell lymphoproliferative disease, possible induction of squamous cell, hyaline cell syringomas, follicular mucinosis, pseudolymphoma- type drug eruptions, and malpighian epitheliomas. Most cutaneous eruptions caused by imatinib do not necessitate discontinuance of imatinib and are usually self limited, despite continued treatment. Administration of oral or topical corticosteroids can ameliorate some of imatinib’s cutaneous side effects.

Adverse drug reactions are a major problem in drug therapy, and cutaneous drug reactions account for a large proportion of all adverse drug reactions. Cutaneous drug reactions are also a challenging diagnostic problem since they can mimic a large variety of skin diseases, including viral exanthema, collagen vascular disease, neoplasia, bacterial infection, psoriasis, and autoimmune blistering disease, among others. Furthermore, determining that a particular medication caused an eruption is often difficult when the patient is taking multiple drugs. In this review, we will describe and illustrate a thoughtful, comprehensive, and clinical approach to the diagnosis and management of adverse cutaneous drug reactions. A morphologic approach to drug eruption includes those that are classified as maculopapular, urticarial, blistering or pustular with or without systemic manifestations. Exanthematous drug eruptions, drug hypersensitivity syndrome, urticaria and angioedema, serum sickness- like reactions, fixed drug eruptions, drug-induced autoimmune blistering diseases, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug-induced acne, acute generalized exanthematous pustulosis, lichenoid drug eruptions and photosensitivity eruptions will be discussed.

BACKGROUND: There is a reported global decrease in the number of clinical trials conducted in recent years. We aimed to determine if this declining trend can be extrapolated to dermatologic clinical trials.
METHODS: We conducted a query of ClinicalTrials.gov for dermatologic clinical trials from 2009 to 2013 for 6 common skin conditions: acne, psoriasis, rosacea, eczema and atopic dermatitis, actinic keratosis, and skin cancer. Results were sorted by condition and number of study subjects. This study did not involve any participants apart from the researchers.
RESULTS: Although there is an increasing trend in the number of trials performed annually, the results were not significant (P=.08). The average number of patients per study has not significantly changed (P=.12), but there was a significant increase in the number of large studies (201+ subjects) conducted over time (P=.002). Although there was significant variation based on dermatologic condition studied (global statistic P=.01), only skin cancer demonstrated a significant change in the number of studies registered annually (β=10.6 studies/year, P=.04).
CONCLUSIONS AND RELEVANCE: The sky does not appear to be falling, at least not yet, with regard to continued development of treatments for patients with skin disease.

J Drugs Dermatol. 2015;14(5):497-500.

Tazarotene is a synthetic retinoid that, depending on the concentration and vehicle, is approved by the US Food and Drug Administration for the topical treatment of acne vulgaris (AV) and plaque psoriasis. Tazarotene is also used as adjunctive treatment for specified clinical manifestations of chronically photodamaged skin (facial fine wrinkling, mottled facial hypopigmentation and hyperpigmentation, and benign facial lentigines), along with comprehensive skin care and photoprotection from sunlight. The gel formulation was released in the United States in 1997, with the cream formulation made available in 2000. Multiple studies are available supporting the effective and safe use of topical tazarotene for each of its indications. This article provides an overview of the pharmacology of topically applied tazarotene, discussing in particular up-to-date information on the efficacy, tolerability, and safety of topical tazarotene for AV, including monotherapy and combination therapy studies. Topical tazarotene 0.1% in both formulations is highly effective in reducing both inflammatory and noninflammatory acne lesions, and can be used in combination with other topical agents, including formulations containing benzoyl peroxide or dapsone 5% gel. Although many patients tolerate the use of topical tazarotene without significant issues or concerns, some patients experience application-site tolerability reactions, which can usually be managed with proper skin care and are less frequent with the cream formulation.

J Drugs Dermatol.2013;12(3 suppl 2):s53-s58.

Introduction: Palmoplantar pustulosis (PPP) is a chronic, recurrent and difficult to treat skin condition characterized by the presence of pustules, erythema, and hyperkeratosis on palms and soles.
Methods: Fifteen subjects with PPP were randomized (2:1) to receive subcutaneous injections of either etanercept 50 mg or a place- bo twice a week for 3 months. All subjects then received the etanercept 50 mg injections twice a week for an additional 3 months.
Results: Etanercept was well tolerated by subjects with PPP. The decrease in median Palmoplantar Pustulosis Area and Sever- ity Index (PPPASI) score from baseline to 24 weeks was statistically significant for subjects treated with etanercept for 24 weeks (P = 0.038, n = 10) but not for subjects in the placebo/etanercept cross-over group (P = 0.125, n = 5). Comparison of changes in PPPASI from baseline to week 12 was not statistically significant for subjects assigned to etanercept or to placebo. Some subjects treated with etanercept presented good clinical improvements in PPP severity whereas others showed an increase in PPP severity
Conclusion: This study showed that etanercept was well tolerated in subjects with PPP and suggests that some PPP subjects might benefit from etanercept therapy. Larger studies are needed to assess PPP response to etanercept including the influence of smoking and the presence or absence of psoriasis outside palms and soles.

Background: Discoid lupus erythematosus (DLE) is a chronic inflammatory disorder mediated by Th1 cells. Apremilast is a novel oral PDE4 enzyme inhibitor capable of blocking leukocyte production of IL-12, IL-23, TNF-a, INF-γ with subsequent suppression of Th1 and Th17-mediated immune responses, and proven clinical efficacy for psoriasis as well as rheumatoid and psoriatic arthritis.
Observations: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) showed a significant (P<0.05) decrease after 85 days of treatment with apremilast 20 mg twice daily in 8 patients with active discoid lupus. The adverse events related to the drug were mild and transient.
Conclusions: This is the first open label study to use apremilast as a treatment modality for discoid lupus. Our observations indicate that apremilast may constitute a safe and effective therapeutic option for DLE.

J Drugs Dermatol. 2012;11(10):1224-1226.

The potential relationship between systemic retinoids used in dermatology and affective disorders is controversial. Acitretin, which is widely used in the treatment of psoriasis is part of this controversy secondary to its chemical relation to isotretinoin, a drug which has been associated with a large number of anecdotal case reports of depression and suicidal ideation. Moreover, an FDA package insert precaution regarding acitretin's association with depression and suicide has elevated the level of concern for patient safety. The objective of this article is to review the evidence in the literature regarding acitretin's association with affective disorders. After 12 years of worldwide use only two cases involving acitretin have been reported in the literature. In addition, despite many anecdotal cases involving isotretinoin, there have been no clinical studies that have proven a causal relationship between isotretinoin and depression or suicidal ideation. For acitretin there have been no systematic clinical studies that examine such a relationship. Moreover, it is notable that the FDA precaution regarding depression and suicide on the package insert of acitretin predates the publication of the aforementioned two cases. This suggests that a relationship between acitretin and affective disorders is a class labeling rather than a scientifically proven association.

J Drugs Dermatol. 2011;10(4):409-412.

Biologics are a mainstay of treatment for many dermatologic conditions, however the high costs can be prohibitive for many patients. A growing market of biosimilar drugs is emerging with the hope of providing patients access to more affordable medications. While the FDA has created an abbreviated licensure pathway for these drugs, states are still in the process of creating regulations regarding their substitution for reference biologics. This article looks to raise awareness of the current federal regulations and the differences among state regulations regarding the use of biosimilars. Fifty percent of states have passed legislation regarding procedures for substitution of biosimilars in the pharmacy. All states require biosimilars to have FDA-approved “interchangeable” status, however states vary on other requirements such as: prescriber and patient notification, pharmaceutical record keeping, publicly-accessible list of interchangeable products, and cost regulations. Some of the issues surrounding biosimilar regulation include difficulty obtaining interchangeability status from the FDA, resistance to the physician notification requirement, and concern for traceability of adverse reactions. Physicians must be aware of current federal and state regulations regarding biosimilars and help inform policy makers of the potential benefits and shortcoming of biosimilar legislation.

J Drugs Dermatol. 2017;16(10):995-1000.

BACKGROUND & AIMS: Nutrition has long been associated with skin health, beauty, integrity and aging through multiple pathways and cofactors implicated in skin biology. The onset and clinical course of various common skin diseases, especially acne, psoriasis, atopic dermatitis, and hair loss, have been suggested to be critically affected by nutrition patterns and habits. The relationship between acne and diet, predominantly the role of high glycemic load diets and dairy consumption have recently gained increased interest. Abnormal nutritional conditions such as obesity or malnutrition often manifest themselves by specific cutaneous features and altered skin function. Skin photoprotection, rendered by various nutrients, is well documented and appropriate nutritional supplementation has been shown to exert beneficial effects upon impaired skin integrity, restore its appearance and promote skin health. It is our intention to provide a comprehensive review of the most recent information on the role of nutrition for common skin diseases and regulation of skin biology.
METHODS: Nutritional clinical studies in dermatology have been reviewed using the MedLine literature source and the terms "diet" or "nutrition" and "skin".
RESULTS & CONCLUSIONS: The data on the relationship between nutrition and skin are until now controversial and much more work is needed to be done to clarify possible etiological correlations.

J Drugs Dermatol. 2013;12(10):1104-1109.

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal demyelinating disease of the brain caused by activation of the John Cunningham virus. It typically occurs in immunocompromised patients, including transplant recipients on immunosuppressant medications, patients receiving chemotherapy for hematologic malignancies, and patients with human immunodeficiency virus. Unfortunately, there is no effective treatment for PML. By contrast, reversible progressive leukoencephalopathy syndrome (RPLS) is a generally treatable disorder that is diagnosed based on clinical symptoms (eg, altered mental status, visual abnormalities, headache, and seizures) and neuroradiographic changes (eg, cerebral edema). It is classically associated with malignant hypertension and immunosuppressive medications. Symptoms usually resolve over time, or with treatment of the underlying cause. Amid the relatively recent withdrawal of efalizumab from the US market because of its association with PML, and the added warning found on ustekinumab describing RPLS as a possible adverse effect, there has been an increasing level of concern in dermatology that biologics and other systemic medications used in the treatment of psoriasis may be related to an increased risk of specific leukoencephalopathies. In this review, we evaluate the association of prebiologics (eg, cyclosporine, methotrexate, acitretin) and biologics (eg, adalimumab, alefacept, efalizumab, etanercept, infliximab, rituximab, and ustekinumab) with the potential risk of developing PML and RPLS.

J Drugs Dermatol. 2013;12(2):e20-e24.

Urea is an important hygroscopic component of the epidermis, where it participates in the maintenance of skin hydration as part of the skin’s source of natural moisturizing factor (NMF) in the outer most layers. Xerotic skin, which is frequently characterized as NMF-deficient, is a unifying trait of dermatoses such as atopic dermatitis (AD), psoriasis, and ichthyosis vulgaris. The reduced hygroscopic potential of pathologically dry skin leads to unregulated transepidermal water loss (TEWL), epidermal hyperproliferation, and inhibited desquamation; all which clinically translate to hyperkeratotic and possibly pruritic skin. Common underlying etiologies link these dermatoses to aberrant expression of genes encoding epidermal structural and catalytic proteins. Intervention of dry skin pathologies with topical moisturizer formulations is a foundational management strategy. For over a century urea-containing formulations have been used in a concentration-dependent manner to restore skin hydration, thin hyperkeratosis, debride dystrophic nails, and enhance topical drug penetration. Recently, urea’s role in skin hydration and repair has expanded to include regulation of epidermal genes necessary for proper barrier function. Taken together, urea’s versatility in topical formulations and broad range of therapeutic mechanism highlights its utility to clinicians and benefit to patients.

J Drugs Dermatol. 2016;15(5):633-639.

Introduction: Pityriasis lichenoides (PL) exhibits a protean clinical presentation, particularly in its overlapping form (OPL) combin- ing aspects of the acute and chronic types. Some patients are drug multiresistant and pose a therapeutic dilemma. The anti-tumor necrosis factor (TNF)-α agent etanercept, was recently introduced as an alternative treatment for psoriasis, rheumatoid arthritis, and psoriatic arthritis.
Case Report: A 65-year-old woman suffered from an overlapping form of pityriasis lichenoides (OPL) for 5 years. Several initial acute episodes were controlled by successive courses of oral antibiotics, topical corticosteroids, and/or psoralen ultraviolet light-A (PUVA) therapy. The disease progressively evolved to a more chronic form. Topical immune response modifiers and corticosteroids, as well as PUVA, ultraviolet light-B (UVB), methotrexate, dapsone, and cyclosporine were introduced, but all proved ineffective. Due to the therapy multiresistance, 2 weekly injections of etanercept were administered. After 2 months, a marked improvement was observed in regards to the patient’s pruritus and inflammation. No treatment-related adverse effects were observed. Therapy was continued for 4 months without any new lesion development. However, 1 month after stopping treatment new OPL lesions recurred.
Conclusion: At the time of publication, this is the first report of the effectiveness of etanercept in OPL. This drug might be consid- ered as a therapeutic alternative for treatment multiresistant OPL.

INTRODUCTION: Dermatologists are becoming more aware of the irritant and allergic potential of laundry detergents that incorporate harsh surfactants and potentially sensitizing ingredients. It is difficult however for the physician to distinguish one laundry detergent from another because the only distinguishing feature advertised tends to be the lack of dyes and fragrances.

DESIGN: A new objective method was developed for measuring the harshness of laundry detergents using a three-pronged laboratory testing approach consisting of zein, corneosurfametry, and cytokine testing. Combing these methods, a Detergent Mildness Index was created which conveniently provides a single value by which products can be compared.

Results: A new mild laundry detergent was formulated with ingredients carefully selected by dermatologists who are experts in con-tact dermatitis. The irritancy potential of the formula was measured using the Detergent mildness index score. Compared to 11 other commercial laundry detergents marketed for sensitive skin, the new formula is measurably the mildest formula.

Discussion: The Detergent Mildness Index provides dermatologists with an objective method to compare commercial laundry deter-gents. Currently the only method available is patch testing, this new test is able to more finely differentiate between products and thus enables more informed recommendations on laundry detergent choices for their patients with sensitive skin.

J Drugs Dermatol. 2017;16(12):1235-1239.

Objectives: Assessment of associations between etanercept treatment and rare adverse events has been limited by the size of clinical trial populations. The authors examined the collective safety of etanercept in clinical trials across approved indications.
Patients and Methods: Forty-nine U.S. and non-U.S. trials of etanercept, involving up to 13,977 patients for approved indications, with final trial reports as of May 2006, were selected from the Amgen Inc. clinical trials database. Exposure-adjusted rates of serious infections, opportunistic infections, malignancies and deaths were reported by trial, indication and dosage.
Results: Rates of serious infections were generally similar between etanercept and controls. Overall rates of opportunistic infections and tuberculosis were low. The standardized incidence ratio (SIR) (95% CI) for malignancy was 1.00 (0.83–1.19) for all etanercept patients across all indications. The SIR for lymphoma for patients with rheumatoid arthritis was 3.45 (1.83-5.89); all other indications reported SIRs similar to those observed in the general population. The SIRs for cutaneous squamous cell carcinoma in patients with psoriasis relative to the general population with high or low sun exposure were 2.09 (1.27-3.22) and 4.96 (3.03-7.66), respectively. SIRs were less than 1.0 for all other indications regardless of sun exposure. Rates of melanoma and basal cell carcinoma were not significantly different from those in the general population. There was no increase in mortality associated with etanercept use relative to control populations.
Conclusion: These data support the overall tolerability of etanercept across approved indications.

J Drugs Dermatol. 2011;10(3):289-300.

BACKGROUND: Topical corticosteroids offer great efficacy in controlling a wide variety of dermatoses. Traditional ointment vehicles are messy and difficult to apply, which might limit adherence. Alternative vehicle formulations such as topical sprays might improve adherence due to their ease of application. The potency of desoximetasone spray is not fully characterized. OBJECTIVE: To evaluate the relative vasoconstrictive potency of desoximetasone 0.25% topical spray formulation. METHODS: This is a randomized, blinded, single-center study comparing the vasoconstrictive properties of desoximetasone 0.25% topical spray to placebo and seven other known potency topical corticosteroid formulations. The primary endpoint was the degree of vasoconstriction measured using a colorimeter device. RESULTS: Thirty-two healthy subjects met eligibility criteria. Desoximetasone 0.25% topical spray (REGWQ Grouping = A) showed a trend toward greater vasoconstrictive potency compared to clobetasol propionate 0.05% spray (REGWQ Grouping = A). No adverse or serious events were reported. Limitations: The trial enrolled 90% females, which may affect the external validity of the study. Different populations may respond differently to desoximetasone spray. CONCLUSIONS: Desoximetasone 0.25% topical spray is a high to super high range of potency (Class I to Class II) steroid formulation. Given the cosmetic acceptability of spray products, we anticipate that this type of product would be highly effective for the treatment of inflammatory diseases in clinical practice.

J Drugs Dermatol. 2017;16(10):972-975.

The 1925 classical observation that vitamin A deficiency leads to squamous metaplasia and epithelial keratinization, coupled with the later finding that excess vitamin A inhibits keratinization of chick embryo skin, set the foundation for the potential therapeutic use of retinoids in cutaneous conditions of keratinization. Significant progress has since been made understanding the molecular biology, biochemistry, pharmacology, and toxicology of vitamin A and its derivatives, collectively named retinoids. Natural and synthetic retinoids are now routinely used to treat acne, psoriasis, skin keratinization disorders, and photodamage. Retinoids also inhibit tumor formation and skin cancer development in experimental systems and in humans. Retinol and retinyl palmitate (RP) are found in cosmetic products and in foods and dietary supplements, which are all considered safe, by inclusion in the Generally Recognized as Safe Substances Database. However, the safety of topical retinoids was questioned in one publication and in a recent National Toxicology Program report of RP-containing topical preparations, suggesting the possible earlier onset of ultraviolet-induced squamous cell carcinomas in the hairless mouse photocarcinogenesis model. This suggestion contradicts a large body of data indicating that topical retinoids are chemoprotective in humans, and it was immediately challenged by new reviews on the safety of RP in general and within sunscreens. This paper will review the preclinical and clinical data supporting the safety and chemopreventive activity of retinoids, with an emphasis on RP, and will examine the experimental systems used to evaluate the safety of topical vitamin A preparations in order to provide perspective relative to human skin.

J Drugs Dermatol. 2013;12(4):458-463.

Taurine plays an important role in brain and retinal development, and has an antiinflammatory and antioxidant function. Taurine chloramine (Tau-Cl) is produced in polymorphonuclear leukocytes via the myeloperoxidase/halide system. We previously demonstrated that Tau-Cl inhibits the production of nitric oxide (NO) and TNF-α in human and murine macrophages activated with IFN-γ in combination with individual Toll-like receptor (TLR) ligands including those for TLR2 and/or TLR4. In the current study, we further explored the effects of Tau-Cl in RAW 264.7 cells stimulated with the TLR9 ligand CpG oligodeoxynucleotide (ODN). Specifically, we examined the effect of CpG ODN plus IFN-γ on the production of NO and TNF-α, and the effect of Tau-Cl on this process. Our findings show that CpG ODN plus IFN-γ-activated RAW 264.7 cells secrete high levels of NO and TNF-α, and that Tau-Cl (0.8 mM) inhibits this effect in a dose-dependent manner, more potently inhibiting the production of NO (99% inhibition) than that of TNF-α (48% inhibition). Nitric oxide synthase (iNOS) protein was also induced by CpG ODN plus IFN-γ, and was also inhibited by Tau-Cl. Furthermore, while CpG ODN plus IFN-γ induced TNF-α and iNOS mRNAs, Tau-Cl transiently suppressed this effect. Taurine itself had no effects on any of these processes. Our findings in a macrophage cell line demonstrate that Tau-Cl inhibits proinflammatory mediators resulting from TLR9 activation, and have implications for the utility of Tau-Cl in scenarios where such activation is deleterious such as in autoimmune conditions or infections in which overwhelming inflammation may occur. CpG ODNs and Tau-Cl both have potential for topical treatment of autoimmune conditions, including psoriasis, vitiligo, and alopecia areata. As CpG ODNs may, under some conditions, up-regulate Tregs, addition of Tau-Cl to CpG ODN topical formulations has potential for improving cancer immunotherapy.

J Drugs Dermatol. 2013;12(5):551-557.

Objective: Evaluate the efficacy and safety of apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, in subjects with recalcitrant moderate to severe atopic dermatitis (AD) or allergic contact dermatitis (ACD).
Research design and methods: This was a proof-of-concept, phase 2, open-label, single institution trial that evaluated the efficacy and safety of apremilast, 20 mg twice daily, for twelve weeks, in ten subjects with either AD and/or ACD. The primary endpoint was a ≥2 point improvement in Investigator Global Assessment (IGA) score after 12 weeks of treatment. Secondary endpoints included a 75% reduction in the Eczema Assessment Severity Index (EASI-75), EASI-50, and the maximum EASI response.
Results: The primary endpoint of improvement in IGA by two or more points was met by 20% of subjects. Ten percent of subjects achieved EASI-75 and another 10% reached EASI-50. All subjects tolerated apremilast well with no serious adverse events or withdrawal due to side effects. Common adverse events associated with apremilast included headache, nausea, and soft stool.
Limitations: This study was limited by its small sample size and lack of a comparison group to serve as a control.
Conclusions: Apremilast was well tolerated in all subjects. Apremilast was minimally effective in AD and ACD and results were inferior to previous trials of apremilast in psoriasis.

J Drugs Dermatol. 2012;11(3):341-346.

BACKGROUND: Tinea pedis is the most common superficial fungal infection. Naftifine hydrochloride is a topical antifungal of the allylamine class, displaying fungicidal activity and clinically significant anti-bacterial and anti-inflammatory effects. Clinical data on topical antifungal therapy using naftifine for tinea pedis in a pediatric population is limited.
OBJECTIVE: To assess trends in efficacy, tolerability, safety, and to quantify the pharmacokinetics (PK) of topical naftifine hydrochloride gel 2% in pediatric subjects with tinea pedis.
METHODS: Twenty-eight subjects (22 pediatric and 6 adult controls) were enrolled and treated in the study. Approximately 2 grams of naftifine hydrochloride gel 2% was applied to each foot (4 grams total) for subjects with tinea pedis. Pharmacokinetic blood and urine samples were collected at various time points throughout the study. Efficacy was assessed based on potassium hydroxide, dermatophyte culture, and signs and symptom results at days 7, 14, and 28. Adverse event information was collected routinely.
RESULTS: The rate and extent of systemic exposure among the pediatric and adult control subjects was low. Adverse events were minimal and were not related to treatment. Positive results were observed as early as day 7; however the proportion of subjects achieving success generally increased over time through day 28 in both treatment groups.
CONCLUSIONS: Naftifine hydrochloride gel 2% was found to be well tolerated and safe. Trends in clinical benefit were observed throughout the treatment period; however, continued improvement in efficacy rates were observed during the post-treatment period.

J Drugs Dermatol. 2015;14(7):686-691.

Background: Tumor necrosis factor inhibitors are valuable tools for dermatologists. As their use increases, rare adverse events are more likely to be encountered.
Objective: We describe one patient who developed sarcoidosis while being treated for psoriasis with etanercept. We sought to review to previously reported cases and further characterize the nature of this reaction.
Methods: A literature search was performed with the key words "sarcoidosis, sarcoid, etanercept, infliximab, adalimumab, granulomatous, and drug reaction." All relevant cases in the English language were included and evaluated for demographic data, duration of therapy prior to developing sarcoid, duration of sarcoid signs/symptoms, treatments used and time to resolution after discontinuation of the drug.
Results: Including the present case, there are 34 cases of sarcoidosis developing during anti-tumor necrosis factor therapy. All previously reported cases were patients with a primarily rheumatologic diagnosis. In all but one case, discontinuation of the drug resulted in complete resolution of symptoms. The lung and surrounding lymph nodes were the areas most commonly affected. The average amount of time between initiation of therapy and onset of symptoms was 22 months. The average time to resolution of symptoms after discontinuation of the drug was 5.2 months.
Limitations: This is a retrospective case review.
Conclusions: These data indicated that sarcoid is a possible adverse effect of tumor necrosis factor inhibitor therapy that should be noted by dermatologists using these drugs. While it has been reported in the rheumatology literature, it may be under-recognized by dermatologists.

J Drugs Dermatol. 2012;11(5):609-612.

SUMMARY BACKGROUND: Many over the counter topical products claim to reverse the signs of cutaneous photo-damage. To date, the two most studied ingredients for improving the texture, tone, and pigmentation of the skin are topical retinoids and hydroquinone.¹
OBJECTIVE: This split face study compares a mass market skincare regimen with a prescription skin care regimen for improvement in photo damaged skin.
METHODS: Twenty-seven subjects with moderate photo damaged facial skin were enrolled.   Each subject was consented and assigned with the mass market anti-aging system (Treatment A) to one side of the face and the prescription anti-aging system (Treatment B or Treatment C) to the other side of the face. Treatment B contained 13 subjects whom did not use 0.025% Retinol cream. Treatment C contained 14 subjects who used a 0.025% Retinol Cream. Subjects had 4 visits over 12 weeks for digital photography and surveys. Photographs were evaluated by blinded physicians.
RESULTS: Physician objective analysis showed all three systems to have a statistically significant clinical improvement in photoaged skin seen in as little as 4 weeks of use. Participant’s surveys rated the mass market system higher than both of the professional systems for visible skin changes, ease of use, and likelihood to recommend to a friend. Twelve of twenty-seven subjects preferred the mass market system for overall improvement while twelve thought each system gave the same improvement.
CONCLUSION: This study demonstrates that a mass marketed skin care system can give similar clinical improvements in photo-aged skin as a professionally dispensed prescription system and the majority of participants preferred the mass-marketed system.

J Drugs Dermatol. 2016;15(1):37-44.

Background: Topical corticosteroids are often considered to have greater safety and poorer efficacy than oral corticosteroids in treating psoriasis and atopic dermatitis. There are limited data for assessing relative efficacy of topical and systemic corticosteroids, however. The concentration of corticosteroid in skin, adjusted for the relative potency of the active compound, may be a predictor of clinical efficacy and can be estimated for both topical and oral administration.

Purpose: To analyze the assumption that oral corticosteroid therapy should be more potent than topical therapy by comparing relative corticosteroid concentrations in the skin expected with topical versus systemic administration.

Methods: The estimated skin concentration of prednisone following oral dosing was calculated based on data showing 70–100% bioavailability and an even tissue distribution. Data on the concentration of corticosteroids found in skin after topical application were obtained from the literature. The relative potencies of corticosteroid molecules were then used to compare skin concentrations of corticosteroid following topical versus oral treatment.

Results: Data derived from the existing literature demonstrated that hydrocortisone 2.5% ointment, triamcinolone 0.1% ointment, and clobetasol 0.05% foam achieved effective skin concentrations greater than the effective concentration achieved by oral prednisone. Betamethasone 0.1% cream achieved effective concentrations in skin within the range created by oral prednisone.

Limitations: This analysis was limited by the paucity of data regarding cutaneous concentrations of corticosteroids after topical application, and by the differing experimental designs utilized in the available studies.

Conclusion: Most topical corticosteroids have the potential to achieve greater effective drug levels in the superficial layers of skin than those achieved with standard doses of oral prednisone. The apparently greater efficacy of oral corticosteroid therapy may be attributable, in part, to poor patient compliance with topical therapy. Systemic alterations in immune function following oral, but not topical, corticosteroid use may also play a role.

Background: Although the exact pathogenesis of vitiligo is not fully understood, it appears to be an autoimmune disease. It is hypothesized that tumor necrosis factor alpha (TNF-α) plays an important role in vitiligo. TNF-α can destroy melanocytes through the induction of various apoptotic pathways. In addition, TNF-α can inhibit melanocyte stem cell differentiation.
Objective: To evaluate the efficacy and safety of treating vitiligo patients with anti-TNF-α agents.
Methods: A total of 6 patients were recruited. All patients had widespread non-segmental vitiligo. Biologics, including infliximab, etanercept, and adalimumab, were given according to treatment regimens used for psoriasis. Photographs were taken at the initial visit, every two months during the therapy and then six months after therapy completion.
Results: All patients completed the treatment; two patients were treated with infliximab, two with etanercept, and two with adalimumab. All of the biologics were well tolerated throughout the treatment period, and none of the patients reported any significant adverse events. Digital images were compared before, during and after treatment. Repigmentation of the vitiliginous areas was not observed in any of the patients. Vitiligo worsened in one patient who was treated with infliximab and developed a psoriasiform rash. However, the remaining patients did not develop any new depigmented patches during treatment or at the six-month follow-up; vitiligo was considered stable in these five patients.
Conclusions: Although the anti-TNF-α agents were well tolerated in all six vitiligo patients, efficacy was not observed. Further evaluation with larger studies may be required.

J Drugs Dermatol. 2012;11(4):534-539.

No abstract details for the moment.

No abstract details for the moment.

Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatologic community. This department may include additional information from the manufacturers, plus reports from physicians who wish to share their clinical experience with these new products. In addition, we will inform our readers about the latest drugs receiving Food and Drug Administration (FDA) approval.

No abstract details for the moment.

Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatologic community. This department may include additional information from the manufacturers, plus reports from physicians who wish to share their clinical experience with these new products. In addition, we will inform our readers about the latest drugs receiving Food and Drug Administration (FDA) approval.

Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatologic community. This department may include additional information from the manufacturers, plus reports from physicians who wish to share their clinical experience with these new products. In addition, we will inform our readers about the latest drugs receiving Food and Drug Administration (FDA) approval.

Clinical Trial Review is a JDD department designed to provide physicians with information on drugs and devices undergoing clinical testing. It is our goal to inform the reader of the status of select drug and device studies relevant to the practice of dermatology before this information is available through standard channels. To participate in or learn more about these and additional trials, visit www.clinicaltrials.gov.