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Background: Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis., Objective: Assess long-term safety of oral apremilast in psoriasis patients., Methods: Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2., Results: The 0 to ≥156-week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156-week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52-week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported., Limitations: This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns., Conclusions: Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Difficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life., Objective: We evaluated the efficacy and safety of apremilast in palmoplantar psoriasis., Methods: A post hoc analysis of data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1 and 2) clinical studies was conducted to determine the effect of apremilast 30 mg twice daily versus placebo at week 16 in a subset of patients with moderate to severe plaque psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis Physician Global Assessment [PPPGA] score ≥1)., Results: Significantly more patients taking apremilast with moderate to severe palmoplantar psoriasis (baseline PPPGA score ≥3) achieved PPPGA score 0 (clear) or 1 (almost clear) compared with placebo at week 16 (48% vs 27%; P = .021). At week 16, 46% of the apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of 0 versus 25% of the placebo group (P < .001); 59% of the apremilast group had a PPPGA score of 0 or 1 with 1-point or more improvement versus 39% receiving placebo (P < .001)., Limitations: This post hoc analysis was limited to 16 weeks and did not assess palmoplantar pustules, lesion localization, or surface area involvement., Conclusion: Apremilast may be a useful oral treatment option for patients with moderate to severe palmoplantar plaque psoriasis., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: In the phase III double-blind Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2, apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in moderate to severe psoriasis., Objective: We sought to evaluate efficacy of apremilast in nail/scalp psoriasis in ESTEEM 1 and 2., Methods: A total of 1255 patients were randomized (2:1) to apremilast 30 mg twice daily or placebo. At week 16, placebo patients switched to apremilast through week 32, followed by a randomized withdrawal phase to week 52. A priori efficacy analyses included patients with nail (target nail Nail Psoriasis Severity Index score ≥1) and moderate to very severe scalp (Scalp Physician Global Assessment score ≥3) psoriasis at baseline., Results: At baseline, 66.1% and 64.7% of patients had nail psoriasis; 66.7% and 65.5% had moderate to very severe scalp psoriasis in ESTEEM 1 and 2. At week 16, apremilast produced greater improvements in Nail Psoriasis Severity Index score versus placebo; mean percent change: -22.5% versus +6.5% (ESTEEM 1; P < .0001) and -29.0% versus -7.1% (ESTEEM 2; P = .0052). At week 16, apremilast produced greater NAPSI-50 response (50% reduction from baseline in target nail Nail Psoriasis Severity Index score) versus placebo (both studies P < .0001) and ScPGA response (Scalp Physician Global Assessment score 0 or 1) versus placebo (both studies P < .0001). Improvements were generally maintained over 52 weeks in patients with Psoriasis Area and Severity Index response at week 32., Limitations: Baseline randomization was not stratified for nail/scalp psoriasis., Conclusion: Apremilast reduces the severity of nail/scalp psoriasis., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Apremilast works intracellularly to regulate inflammatory mediators., Objective: ESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis., Methods: This phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ(2) test; continuous end points used analysis of covariance., Results: In all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was -88% to -81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period., Limitations: Data were limited to 52 weeks and may not generalize to nonplaque psoriasis., Conclusions: Apremilast was effective in moderate to severe plaque psoriasis., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials.

Data from 104 subjects with tinea cruris or tinea corporis were evaluated in this double-blind, randomized study. The subjects applied naftifine cream 1% or econazole nitrate cream 1% to affected areas twice daily for 4 weeks. After 1 week of treatment naftifine had an overall cure rate of 19% compared with 4% for econazole (p = 0.03). A difference in favor of naftifine, although not statistically significant after the first week, persisted throughout treatment. Two weeks after the end of treatment both medications had overall cure rates of approximately 80%. Three percent of the naftifine-treated subjects had side effects compared with 13% of the econazole-treated subjects. In two subjects using econazole, the side effects were severe enough to warrant discontinuation of treatment.