Andrea Chiricozzi MD,a Francesca Specchio MD,b Annunziata Dattola MD,b Monika Fida MD,c
Luca Bianchi MD,b and Sergio Chimenti MD,b
and Rosita Saraceno MDb
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.
Zinc pyrithione (ZPT) is an active material that has been used for over 50 years to effectively treat dandruff and seborrheic dermatitis (D/SD). It has become the most common material for that purpose, its use has expanded to include other skin benefits such as skin hygiene. However, there is much about ZPT that is unappreciated. It is a rationally developed molecule that was modeled after the naturally occurring antimicrobial aspergillic acid. The molecular basis for its antifungal activity has been elucidated. The efficacy of ZPT originates from two attributes. First, it has a very broad antimicrobial spectrum of activity, including fungi, gram-positive and -negative bacteria. Second, the material has very low solubility, resulting in formulation and delivery as a particulate material, which has distinct performance advantages. The particles are deposited and retained on the target skin surfaces even when delivered from rinse-off products. These particles slowly release molecularly active material to interact with the surface fungal and bacteria cells to control their population, functioning as slow-release reservoirs to provide extended and persistent benefits. This particulate nature, though, results in complex pharmaceutics to realize the full efficacy benefits; it is common to see products with the same ZPT level having widely varying levels of clinical performance. Several product matrix-determined factors directly impact resultant benefits: ZPT must be retained on the skin surface achieving uniform spatial distribution laterally as well as within hair follicles (especially on scalp); ZPT must be maintained as a physically stable dispersion in product; ZPT must be maintained in a chemically active form as there are many chemical
reactions that can occur that can harm ZPT bioactivity. The benefits achievable by employing ZPT require significant pharmaceutics expertise to realize the full benefits of this active material.
J Drugs Dermatol. 2016;15(2):140-144.
Eric P. Sorensen BS,ab Haitham Algzlan MD,a Shiu-chung Au MD,a Caren Garber BA,ac Kristina Fanucci BS,ac Michelle Bichchau Nguyen MD MPH,ac and Alice B. Gottlieb MD PhDac
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.
Joseph F. Fowler Jr. MD,a Adelaide A. Hebert MD,b Jeffrey Sugarman MD PhDc
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.
Catherine D. Buzney MA,a Alice B. Gottlieb MD PhD,a,b David Rosmarin MDa,b
Type 2 helper T cell (Th2)-mediated inflammation plays a critical role in the pathogenesis of allergic asthma and atopic dermatitis (AD). Recent research focusing on the suppression of the Th2 axis with targeted inhibitors in atopic disease is showing promising early results. In particular, the simultaneous blockage of interleukin (IL)-4 and IL-13 has successfully mitigated symptoms of allergic asthma and AD in preliminary clinical trials. Given the current therapeutic challenges of treating these chronic and severe diseases, this review brings to light new data demonstrating that agents targeting IL-4 and IL-13 are relatively safe and effective medications in blocking the inflammatory cascade responsible for allergic asthma and atopic dermatitis.
J Drugs Dermatol. 2016;15(2):165-171.
Zoe Diana Draelos MD,a Linda F. Stein Gold MD,b Dedee F. Murrell MD,c Matilda H. Hughes CCRA,d and Lee T. Zane MDd
BACKGROUND: Two post hoc analyses assessed the antipruritic activity of crisaborole topical ointment, 2% (crisaborole; Anacor Pharmaceuticals,
Inc., Palo Alto, CA), a first-in-class boron-based phosphodiesterase-4 inhibitor in development for treatment of mild to moderate atopic dermatitis (AD).
METHODS: Two pooled analyses included data from 4 studies evaluating crisaborole in AD (study 1, phase 1b, systemic exposure, safety, and pharmacokinetics [PK] under maximal-use conditions in children and adolescents; study 2, phase 2a, safety and PK in adolescents;
study 3, phase 2a, efficacy and safety in adults; study 4, phase 2, efficacy and safety in adolescents). Pooled data from studies 1 and 2 included whole body assessments; studies 3 and 4 included target lesion assessments. Pruritus severity was evaluated using a 4-point rating scale (0=none to 3=severe). Efficacy assessments included percent change from baseline in pruritus severity scores at days 8 (first pooled assessment), 15, 22, and 29 (whole body assessments) or days 15 (first pooled assessment), 22, and 29 (target lesions). Paired t-tests comparing change from baseline against zero were used to calculate P values. Categorical shifts in pruritus severity were also assessed (no to mild pruritus, 0–1.5; moderate to severe pruritus, 2–3).
RESULTS: In the pooled analysis of studies 1 and 2 (N=57), the percent change from baseline in pruritus severity scores were 63.0% and 64.9% at days 8 and 29, respectively (P<0.001 for each). Similar results were observed in the pooled analysis of studies 3 and 4 (N=67). In both analyses, most patients had mild to no pruritus from the first time point assessed through the remainder of treatment.
CONCLUSIONS: Treatment with crisaborole topical ointment, 2% resulted in statistically significant reductions in pruritus severity at the first time point evaluated in both analyses. These findings provide preliminary evidence of the antipruritic activity of crisaborole topical ointment, 2%.
J Drugs Dermatol. 2016;15(2):172-176.
Leon H. Kircik MD,a Varsha Bhatt PhD,b Gina Martin MOT,b and Radhakrishnan Pillai PhDb
The use of fixed combinations in acne vulgaris (acne) is very common, however comparative clinical trial data are limited. Cutaneous tolerability can influence patient compliance, and concerns about skin irritation with topical acne treatments have lead to a number of comparative split-face studies.
Recently, a new fixed combination product was introduced (clin 1.0%-BP 3.75% gel) that was shown to be effective in reducing both inflammatory and noninflammatory lesions in moderate to severe acne. Here, we assess the tolerability of clin 1.0%-BP 3.75% gel compared with adap 0.1%-BP 2.5% gel in healthy volunteers with no apparent facial redness or dryness over 21-days, using a split-face methodology.
Especially over the first two weeks of treatment, clin 1.0%-BP 3.75% gel was more tolerable than adap 0.1%-BP 2.5% gel, with statistically significant differences in cumulative change from baseline starting as early as day 8 (dryness) and day 9 (erythema), and composite index on days 8-12 and 16. Transepidermal water loss was less with clin 1.0%-BP 3.75% gel, although the difference was not statistically significant.
J Drugs Dermatol. 2016;15(2):178-182.
A.B. Kimball MD MPH,a E. Edson-Heredia MPH,b B. Zhu PHD,b J. Guo MS,b T. Maeda-Chubachi MD PHD,b W. Shen PHD,b and M.T. Bianchi MD PHDa
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.
BACKGROUND: Acne vulgaris is a common, chronic skin disease that requires long-term therapy. Oral antibiotics are a mainstay of treatment, but extended use is associated with the development of bacterial resistance. Topical therapies are often combined with oral antibiotics to achieve an initial improvement, after which the oral agents may be discontinued and the topical therapy used as maintenance.
OBJECTIVE: To assess the safety and efficacy of combination therapy with dapsone 5% gel with oral doxycycline hyclate 100mg, followed by monotherapy with dapsone 5% gel in improving and maintaining response in patients with moderate to severe acne.
METHODS: In this open-label study, all patients applied dapsone 5% gel twice daily along with doxycycline hyclate 100mg once daily for 12 weeks. Subjects who achieved a qualifying improvement at week 12 continued to the second phase of the study in which they applied only dapsone 5% gel twice daily for maintenance therapy of 12 more weeks. Subjects were evaluated for safety and efficacy at weeks 4, 8, 12, 16, 20, and 24.
RESULTS: All subjects (n=30) in the initial phase qualified to enter the maintenance phase. 82% of participants maintained their treatment response (Investigator’s Global Assessment score) at week 24. The regimen was safe and well tolerated.
CONCLUSIONS: The combination oral doxycycline hyclate 100 mg with topical dapsone 5% gel twice daily is an effective and well-tolerated regimen to treat moderate to severe acne vulgaris. After discontinuation of doxycycline, topical dapsone 5% gel is effective at maintaining a therapeutic response. These data suggest that topical dapsone 5% gel can be used effectively for long-term acne maintenance treatment without the risk of developing antibiotic resistance.
J Drugs Dermatol. 2016;15(2):191-195.
Andrew F. Alexis MD MPH,a Cheryl Burgess MD,b Valerie D. Callender MD,c Jo L. Herzog MD,d Wendy E. Roberts MD,e Eric S. Schweiger MD,f Toni C. Stockton MD,g and Conor J. Gallagher PhDh
BACKGROUND: Topical dapsone gel, 5% is approved for treatment of acne vulgaris but has not been studied specifically in women with skin of color (SOC; Fitzpatrick skin types IV, V, or VI).
OBJECTIVE: Evaluate safety and efficacy of dapsone gel, 5% applied topically twice daily for 12 weeks in women with SOC.
METHODS: Females with SOC aged 18 years and older with facial acne participated in a multicenter, open-label, single-group, 12-week pilot study of twice-daily monotherapy with dapsone gel, 5%. The investigator-rated 5-point Global Acne Assessment Score (GAAS) was used to assess efficacy. The impact of acne on subjects was assessed using the validated Acne Symptom and Impact Scale (ASIS).
RESULTS: The study enrolled and treated 68 women with SOC and facial acne. GAAS decreased significantly from baseline to week 12 (mean, -1.2 [95% CI, -1.4, -1.0]; P<.001), a 39.0% improvement. Overall, 42.9% of subjects were responders based on a GAAS of 0 or 1 at week 12. Subjects also experienced significant reductions in mean total lesions (52% decrease), inflammatory lesions (65%), and comedo counts (41%; all P<.001). Dapsone gel, 5% monotherapy was associated with significant improvement in subject-assessed acne signs (P<.001) and impact on quality of life (QOL; P<.001), based on ASIS. Dapsone gel, 5% used twice daily was well tolerated, with no treatment-related adverse events. The local dermal tolerability scores tended to remain stable or decrease from baseline to week 12.
CONCLUSIONS: Monotherapy with dapsone gel, 5% administered twice daily was safe and effective for treatment of facial acne in women with SOC. Significant improvement in overall acne severity and both inflammatory lesions and comedones was observed. Further, study subjects reported considerable improvement in both acne signs and impact on QOL.
J Drugs Dermatol. 2016;15(2):197-204.
Macrene Alexiades MD PhD
Jasmonates are plant-derived hormones from linoleic acid that were originally isolated from jasmine, and which are involved in plant stress regulation, wound repair and defense. They have been demonstrated through in vitro and in vivo studies to possess anti-neoplastic properties. Most recently, a novel jasmonate analog was developed, tetrahydrojasmonic acid (LR2412), which possesses favorable characteristics for cutaneous application and which induces improvements in epidermal hyaluronic acid and thickness. Clinical application of LR2412 to facial skin has been demonstrated to reduce the appearance of wrinkles and photoaging. In this issue, a clinical trial is published demonstrating the results of topical application of this agent for th cosmetic treatment of wrinkle appearance, poor texture and large pores.
J Drugs Dermatol. 2016;15(2):206-207.
Macrene Alexiades MD PhD
BACKGROUND: The jasmonates are a novel class of plant-derived anti-aging compounds. Among these, LR2412-Cx (tetrahydrojasmonic acid, Visionnaire) has been demonstrated to reduce photoaging and the appearance of wrinkles, as well as to upregulate collagens, hyaluronic acid and fibrillin.
OBJECTIVE: To clinically study the cosmetic effects of a novel jasmonate complex LR2412-Cx in the treatment of visible skin aging.
METHODS: LR2412-Cx was evaluated in a 15-subject open-label prospective clinical trial for the treatment of fine wrinkle appearance, texture, and pores. Subjects were evaluated by an investigator at baseline, day 1, day 3, and week 6 with the Alexiades comprehensive grading scale of skin aging, and introducing a novel pore-grading scale and subject quality of life assessments.
RESULTS: The mean (SEM) at baseline and at week 6 following twice-daily application were: for the appearance of wrinkles 2.91 (0.12) and 2.70 (0.10); for texture 2.91 (0.10) and 2.55 (0.10); and for pores 3.29 (0.08) and 2.46 (0.09), respectively. The differences in all 3 categories at all follow-up intervals were statistically significant (P<.005). The percentage improvement in investigator-assessed grades relative to baseline at day 1, day 3, and week 6 were: 2.3%, 4.9%, and 7.4% for the appearance of wrinkles, 5.7%, 9.4%, and 12.4% for texture, and 14.2%, 21.6% and 25.2% for pores, respectively. No significant untoward effects were reported.
CONCLUSION: Visionnaire LR2412-Cx is a novel jasmonate-containing compound that is safe and effective for the cosmetic treatment of fine wrinkle appearance, texture, and pores of the facial skin.
J Drugs Dermatol. 2016;15(2):209-215.
Carl R. Thornfeldt MDa and Ronald L. Rizer PhDb
INTRODUCTION: Research has shown that a disrupted stratum corneum permeability barrier coupled with chronic inflammation induce signs of extrinsic aging (photoaging). An novel herbal-based three product cosmeceutical regimen used to reverse these two anomalies that does not contain retinol, soy, niacinamide, tea, L-ascorbic acid or esters, hydroxy acids, tocopherol, or growth factors was tested in six human clinical trials to determine effectiveness and safety in reversing photoaging.
MATERIALS AND METHODS: Six randomized split face, double blind, prospective, controlled clinical trials involving a total of 110 subjects compared a cosmeceutical blend of novel herbs in regimens consisting of one to three products to several common antiaging topical treatments. These comparative products include prescription tretinoin, physician strength idebenone, kinetin, polyhydroxy, lactic and glycolic acids in reversing signs of photoaging.
RESULTS:The novel cosmeceutical blend regimen showed superior efficacy and safety in all six trials.
DISCUSSION: These trials substantiate that herbs not used in common antiaging products effectively and safely mitigate and reverse photoaging signs and symptoms. The novel concept of treating photoaging and preventing its progression by repairing and optimizing the stratum corneum barrier, while reversing and inhibiting chronic cutaneous inflammation, has now been proven.
J Drugs Dermatol. 2016;15(2):218-223.
Brian Berman MD PhD,a,b Charles Ellis MD,c and Craig Elmets MDd,*
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.
Adam Friedman MD,a Kim Waite BSc,b Staci Brandt PA-C MBA MSMR, c and Matthew H. Meckfessel PhDb
Nonadherence to topical acne therapies is a major contributing factor to poor treatment outcomes. Multiple contributing factors have been identified, including a lack of perceived efficacy and fear of side effects. A fixed-dose combination gel of adapalene/benzoyl peroxide
gel, 0.1%/2.5% (A-BPO) is an efficacious and safe treatment for a range of acne severities in patients as young as 9 years old. A meta-analysis of 14 clinical studies involving A-BPO was conducted to assess the 4 week efficacy and overall tolerability of this treatment.
Over 2,300 subjects were included in the analysis. Mean total, inflammatory, and non-inflammatory lesion counts decreased at 4 weeks by 40.8%, 46.2%, and 37.5%, respectively. Worst post-baseline tolerability scores for stinging/burning, dryness, scaling, and erythema were none or mild for a majority of subjects. The result of this meta-analysis add to the body of literature supporting the use of A-BPO in a variety of acne patients and shows that A-BPO provides meaningful clinical results within 4 weeks and will be well-tolerated for a majority of patients. With a demonstrable quick onset of action and high tolerability, A-BPO may improve adherence, and ultimately treatment outcomes, by addressing factors that contribute to nonadherence.
J Drugs Dermatol. 2016;15(2):231-236.