Volume 16 | Issue 10
Apremilast and Narrowband Ultraviolet-B Combination Therapy for Treating Moderate-to-Severe Plaque Psoriasis
Jerry Bagel MD MS, Elise Nelson LPN, Brian R. Keegan MD PhD|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.
Cost-Effectiveness Analysis of Ixekizumab vs Etanercept and Their Manufacturer-Recommended Dosing Regimens in Moderate to Severe Plaque Psoriasis
Jeremy Udkoff MA MAS and Lawrence F. Eichenfield MD|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.
A Randomized, Double-Blind, Placebo-Controlled Study of the Vasoconstrictor Potency of Topical 0.25% Desoximetasone Spray: A High to Super High Range of Potency (Class I to Class II) Corticosteroid Formulation
Elias Oussedik BS,a Mohammed D. Saleem MD,a Steven R. Feldman MD PhDa,b,c|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.
Zuxu Yao PhD,a Ronald Moy MD,b Talisha Allen BS,a and Burkhard Jansen MDa|INTRODUCTION: A number of diagnoses in clinical dermatology are currently histopathologically confirmed and this image recognition–based confirmation generally requires surgical biopsies. The increasing ability of molecular pathology to corroborate or correct a clinical diagnosis based on objective gene expression, mutation analysis, or molecular microbiome data is on the horizon and would be further supported by a tool or procedure to collect samples non-invasively. This study characterizes such a tool in form of a ‘bladeless’ adhesive patch-based skin biopsy device. METHODS: The performance of this device was evaluated through a variety of complementary technologies including assessment of sample biomass, electron microscopy demonstrating the harvesting of layers of epidermal tissue, and isolation of RNA and DNA from epidermal skin samples. Samples were obtained by application of adhesive patches to the anatomical area of interest. RESULTS: Biomass assessment demonstrated collection of approximately 0.3mg of skin tissue per adhesive patch and electron microscopy confirmed the nature of the harvested epidermal skin tissue. The obtained tissue samples are stored in a stable fashion on adhesive patches over a wide range of temperatures (-80oC to +60oC) and for extended periods of time (7 days or more). Total human RNA, human genomic DNA and microbiome DNA yields were 23.35 + 15.75ng, 27.72 + 20.71ng and 576.2 + 376.8pg, respectively, in skin samples obtained from combining 4 full patches collected non-invasively from the forehead of healthy volunteers. DISCUSSION: The adhesive patch skin sampling procedure is well tolerated and provides robust means to obtain skin tissue, RNA, DNA, and microbiome samples without involving surgical biopsies. The non-invasively obtained skin samples can be shipped cost effectively at ambient temperature by mail or standard courier service, and are suitable for a variety of molecular analyses of the skin microbiome as well as of keratinocytes, T cells, dendritic cells, melanocytes, and other skin cells involved in the pathology of various skin conditions and conditions where the skin can serve as a surrogate target organ.
J Drugs Dermatol. 2017;16(10):979-986.
Efficacy of Isotretinoin and Acitretin in Treatment of Frontal Fibrosing Alopecia: Retrospective Analysis of 54 Cases
Adriana Rakowska MD PhD,a Agnieszka Gradzińska MD,a Małgorzata Olszewska MD PhD,a and Lidia Rudnicka MD PhDb|This study aimed to assess the efficacy of systemic retinoids in treating frontal fibrosing alopecia (FFA). It was based on a retrospective analysis of 54 female patients with FFA treated with: oral isotretinoin at the daily dose of 20 mg (29/54) or acitretin at the daily dose of 20 mg (11/54) or with oral finasteride 5 mg/daily (14/54). The study was conducted between 2007 and 2017. The basic of the study is the measurement of distance between the frontal hairline and the glabellar crease prior to the commencement of treatment and after 6, 12, and 24 months. The treatment with systemic retinoids lasted between 12 and 16 months (the mean duration of treatment was 13.5 months). The primary treatment goal was defined as no further progression of disease after 12 months of treatment, while the secondary treatment goal was defined as no further progression of disease following the discontinuation of systemic retinoids. The primary treatment goal was achieved by 76% (23/29) of patients treated with isotretinoin, 73% (8/11) of patients treated with acitretin, and 43% (6/14) of patients treated with finasteride. The secondary treatment goal was achieved by 72% (21/29) of patients treated with isotretinoin, 73% (8/11) of patients treated with acitretin, and 43% (6/14) of patients treated with finasteride. Thus, the administration of systemic retinoids may be beneficial for the stabilization of frontal hairline in patients with FFA.
J Drugs Dermatol. 2017;16(10):988-992.
Katerina Yale BA,a Olabola Awosika MD MS,b Monica Rengifo-Pardo MD,a,b and Alison Ehrlich MD MHSa,b|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.
Evaluation of Risk of Major Adverse Cardiovascular Events With Biologic Therapy in Patients With Psoriasis
Robert Bissonnette MD,a Francisco Kerdel MD,b Luigi Naldi MD,c Kim Papp MD,d Claudia Galindo MD,e Wayne Langholff PhD,f K. L. Tang PhD,f Philippe Szapary MD MSCE,f Steven Fakharzadeh MD PhD,e Bhaskar Srivastava MD PhD,e Kavitha Goyal MD,e and Alice B. Gottlieb MD PhDg|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.
Raza Aly PhD,a Aditya K. Gupta MD PhD,b,c Tate Winter PhD,d Lee T. Zane MD,e Tracey Vlahovic DPMf|Toenail onychomycosis is a chronic fungal infection that often requires prolonged treatment in order to effectively manage pathogenic organisms and obtain a clear nail. Traditionally, certain clinical features of onychomycosis, including the presence of substantial lateral disease, focal fungal masses, yellow/brown streaks, and extensive nail involvement (ie, >50%), indicate a poor treatment prognosis and have proven difficult-to-treat with oral or traditional topical therapies. Owing to the novel features of topical tavaborole, we sought to understand the potential utility of tavaborole in difficult-to-treat onychomycosis. A blinded, post-hoc assessment of Phase III trials was conducted, focusing on initial presentation, midpoint assessment (24 weeks), and final outcomes (52 weeks) in subjects identified as having difficult-to-treat onychomycosis and treated for 48 weeks with once-daily application of either tavaborole 5% solution or vehicle. Our post-hoc analysis identified 84 difficult-to-treat cases (tavaborole 5%; n=60; vehicle, n=24) in subjects with toenail onychomycosis due to Trichophyton rubrum or Trichophyton mentagrophytes. No subjects identified as difficult-to-treat and treated with vehicle achieved a complete cure, while 6 subjects treated with tavaborole 5% attained a completely clear nail and negative mycology. Similarly, 7 subjects treated with tavaborole 5% solution achieved an almost complete cure (≤10% involvement and negative mycology) while 1 subject on vehicle achieved an almost complete cure. We present a case series of 4 patients, of varying age and difficult-to-treat clinical features, which responded positively to tavaborole 5% solution. Three of the subjects achieved complete cure after being treated with tavaborole 5%, with one additional subject (an 88-year-old female) achieving an almost complete clear nail by treatment end. The outcomes presented here may not be reflective of patients that may present with these clinical characteristics. Additional investigations would be useful in order to assess the value of topical tavaborole 5% solution in difficult-to-treat clinical presentations of onychomycosis.
J Drugs Dermatol. 2017;16(10):1016-1021.
Pharmacokinetic Comparison of Once-Daily Topical Minocycline Foam 4% vs Oral Minocycline for Moderate-to-Severe Acne
Terry M Jones MD,a Herman Ellman MD,b Tina deVries PhDb|OBJECTIVE: To characterize minocycline pharmacokinetics and relative bioavailability following multiple-dose topical administration of minocycline hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral administration of minocycline HCl extended-release tablets (Solodyn®) in subjects with moderate-to-severe acne. METHODS: A Phase 1, single-center, nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90% white, and 60% females) who had moderate-to-severe acne. Subjects were assigned to first receive a single oral dose of a minocycline HCl extended-release tablet (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical minocycline foam 4% was applied, once daily for 21 days. Serial blood samples were obtained before and after administration of oral minocycline and each topical application of minocycline foam 4% on days 1, 12, and 21. RESULTS: Following oral administration of minocycline (approximately 1 mg/kg), plasma minocycline concentration increased until 3 hours, followed by a log-linear decrease over the remainder of the 96-hour sampling period. Following topical application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma minocycline concentration was very low, with geometric mean Cmax values ranging from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall, minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower than that with oral minocycline. There was no evidence of minocycline accumulation over the 21 days of topical application of minocycline foam 4%. Topical minocycline foam 4% appeared to be safe and well tolerated, with no serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or TEAEs that led to treatment discontinuation. CONCLUSION: Once-daily topical application of minocycline foam 4% did not lead to significant systemic exposure to minocycline. It appears to be a well-tolerated treatment option for individuals with moderate-to-severe acne.
J Drugs Dermatol. 2017;16(10):1022-1028.
Improvement of Actinic Keratoses Using Topical DNA Repair Enzymes: A Randomized Placebo-Controlled Trial
Marie Stoddard BS,a Jennifer Herrmann MD,b,c,d Lauren Moy MD,eand Ronald Moy MDb,c|Background: Actinic keratoses (AKs) are proliferations of abnormal keratinocytes, which may progress into non-melanoma skin cancers. Although multiple treatment modalities exist for AKs, their incidence continues to rise, making new methods of both prevention and treatment necessary. DNA repair enzymes have been shown to reverse sun-damage, resulting in reduced rates of AKs and non-melanoma skin cancer (NMSC) in specific patient populations. Objective: We investigated the efficacy of a topical DNA repair enzyme lotion as a field therapy for AKs. Methods: In a single center, randomized double-blind study, we randomly assigned 15 patients with AKs on their face or scalp to receive topical DNA repair enzyme lotion or placebo (Eucerin Professional lotion). Lotion was self-applied to a treatment field twice daily for 8 consecutive weeks. Complete clearance (primary outcome) was assessed at week 8, and local reactions were quantitatively measured. Follow-up at week 12 assessed for continued clearance of AKs. Results: Thirteen subjects completed the trial. Compared to baseline, patients who used the repair enzyme had significantly fewer AKs than those using the control lotion after 8-weeks treatment. Specifically, there was a 46.6% percent decrease in AKs the DNA repair enzyme lotion group compared to a 32.7% decrease in the placebo group. Significance between the two groups was noted at the12 week follow-up, where there was an additional 29.2% decrease in AK percentage in the DNA repair enzyme group, while the placebo group had a 31.4% increase in AKs (P=0.0026). On final self-assessment, 85% of subjects reported being at least “satisfied” with the ability of the medication to decrease their AK burden. No side effects were reported. Conclusion: These results suggest that topical DNA repair enzymes may help reduce the number of AKs in individuals with moderate-to-severe photodamaged skin. Additionally, there may be a lasting effect of the DNA repair if application is discontinued. Further, cutaneous malignancies were not detected in any of the subjects during the study period. Despite the brevity of the study, these preliminary results suggest the role of DNA repair enzymes for not only treatment, but also skin cancer prevention. Further study and more objective evaluation measures are required for definitive conclusions to be drawn.
J Drugs Dermatol. 2017;16(10):1030-1034.
Kristin Totoraitis BS,a Cynthia M. Magro MD,b Adam Friedman MDc|A previously healthy 68-year-old male presented with a rash on his right lower leg. The lesions had spread along the leg since onset 9 days prior, and the patient reported localized soreness and pruritus. He denied systemic symptoms including fever, fatigue, myalgia, joint pain, and recent illness. Physical examination revealed a serpiginous, purpuric eruption on the anterior and posterior right thigh and lower leg. A 4mm punch biopsy from the right lower leg revealed a Th2 dominant process reflective of a type IV delayed hypersensitivity reaction. Superficial and deep angiocentric and eccrinotropic lymphocytic infiltrate and tissue eosinophilia were noted. Degranulated eosinophils forming ‘flame figures’ were also identified with accompanying mural edema and red blood cell extravasation. Further evaluation revealed an elevated antistreptolysin O antibody, though the remainder of the work up was unremarkable. Clinicohistopathologic correlation supported the diagnosis of Blaschkolinear purpuric Wells’ Syndrome. This case highlights a unique presentation of a rare inflammatory dermatosis, and serves as a reminder that given Wells’ can be associated with underlying malignancy, an age appropriate work up, based on patient history and presentation, may be warranted.
J Drugs Dermatol. 2017;16(10):1036-1038.
Autoimmune Progesterone Dermatitis: A Diagnosis to Consider in a Patient With Cyclical Cutaneous Eruptions
Alexa B. Steuer MPH,a,b Sharon Scherl MD,c and Robin Ashinoff MDb,d|Autoimmune progesterone dermatitis (APD) is a cyclical cutaneous reaction to progesterone, with symptoms that typically begin 3-10 days before the onset of menstrual flow and end 1-2 days into menses. The symptoms vary in severity from barely visible to anaphylaxis, but most often include an eczematous eruption, erythema multiforme, urticaria, folliculitis, and angioedema. This is a rare disorder with only a handful of documented cases. The pathogenesis of this condition remains unknown and significant variations in the presentation and severity of symptoms complicates its diagnosis. Treatment seeks to inhibit progesterone secretion through suppression of ovulation, but it may be unsuccessful. We present a case of autoimmune progesterone dermatitis that eluded diagnosis for several years, and subsequently the patient was completely controlled with oral contraceptive pills.
J Drugs Dermatol. 2017;16(10):1040-1042.
Camila Antia MD, Leah Persad DO, Ali Alikhan MD|Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe and potentially life threatening adverse drug reaction. To help identify DRESS, several criteria have been established; however, there is still a lack of consensus on diagnosis, and clinical judgment is paramount. Here we describe a 24-year-old female who presented with a cutaneous eruption, fever, lymphadenopathy, eosinophilia, facial edema, and elevated liver enzymes four and a half weeks after a 10-day course of Trimethoprim/sulfamethoxazole (TMP/SMX). We used both the RegiSCAR and J-SCAR criteria to show the validity of classifying this case as DRESS, we also comment on the only other three cases, published to date, that had been reported as TMP/SMX induced DRESS. DRESS can be a difficult diagnosis due to its diverse symptomatology and delayed presentation – therefore, high suspicion and exclusion of other causes is key. Use of validated diagnostic criteria can aid the clinician in this regard. In the absence of a well-established therapy, early recognition, withdrawal of suspected drug(s), and supportive care play a crucial role in the management of DRESS.
J Drugs Dermatol. 2017;16(10):1043-1046.
Development of Halo Nevi in a Lung Cancer Patient: A Novel Immune-Related Cutaneous Event from Atezolizumab
Mathew R. Birnbaum BS,*a Michelle W. Ma MD,*a Michael A. Casey MD,b Bijal D. Amin MD,b Mark Jacobson MD,b Haiying Cheng MD PhD,c and Beth N. McLellan MDa *Authors contributed equally|Immunotherapy-induced vitiligo is an immune-related adverse event (irAE) observed in metastatic melanoma patients treated with immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) pathways. To date, the development of leukoderma, poliosis, and halo nevi during immunotherapy has largely been reported in metastatic melanoma patients. We report a case of immunotherapy-induced leukoderma presenting as halo nevi in a patient with non-small cell lung cancer (NSCLC) treated with atezolizumab, a programmed cell death ligand (PD-L1) antibody. Immunotherapy-induced vitiligo in metastatic melanoma patients may be associated with improved survival, but it remains to be determined whether its occurrence in non-melanoma cancers has the same prognostic significance.
J Drugs Dermatol. 2017;16(10):1047-1049.
Helena A. Jenkinson MD,a Alan E. Siroy MD MPH,b Adrienne Choksi MDc|Numerous cutaneous manifestations have been associated with use of BRAF inhibitors, including two previously reported cases of granuloma annulare (GA) eruptions associated with vemurafenib therapy. Both of these patients were being treated for metastatic melanoma. In this report, we describe the case of a 71-year-old man who developed classic GA lesions while being treated with vemurafenib monotherapy for nonmelanoma cancer, specifically metastatic lung adenocarcinoma positive for BRAF V600 mutation.
J Drugs Dermatol. 2017;16(10):1050-1052.