Efficacy and Safety of Apremilast in Patients With Moderate Plaque Psoriasis With Lower BSA: Week 16 Results from the UNVEIL Study
August 2017 | Volume 16 | Issue 8 | Original Article | 801 | Copyright © August 2017
Bruce Strober MD PhD,a Jerry Bagel MD,b Mark Lebwohl MD,c Linda Stein Gold MD,d J. Mark Jackson MD,e Rongdean Chen PhD,f* Joana Goncalves MD,f Eugenia Levi PharmD,f and Kristina Callis Duffin MD MSg
aUniversity of Connecticut, Farm ington, CT, and Probity Medical Research, Waterloo, Ontario, Canada bPsoriasis Treatment Center of Central New Jersey, East Windsor, NJ cIcahn School of Medicine at Mount Sinai, New York, NY dHenry Ford Health System, West Bloomfield, MI eUniversity of Louisville, Forefront Dermatology, Louisville, KY fCelgene Corporation, Summit, NJ gUniversity of Utah, Salt Lake City, UT *Employed by Celgene Corporation at the time of study conduct.
approximately 1% of total BSA. For the 6-point sPGA, clinicians score the severity of each of the 3 primary signs of plaques of all involved areas: erythema, scaling, and plaque elevation.13 Scores for each assessment are averaged and rounded to the nearest whole number for the nal sPGA score. Based on eligibility criteria, baseline PGAxBSA values could range from 15 to 30. Other efficacy end points at week 16 included mean change from baseline in Dermatology Life Quality Index (DLQI) total score; percentage of patients achieving sPGA score of 0 (clear) or 1 (almost clear); percentage of patients achieving score of 0 (clear) or 1 (very mild) on the Patient’s Global Assessment (PtGA) scale (0 [clear] to 4 [severe]); mean change from baseline in pruritus visual analog scale (VAS) score; percentage of patients achieving Scalp Physician’s Global Assessment (ScPGA) score of 0 (clear) or 1 (minimal) with a ≥2-point reduction from baseline in patients with ScPGA ≥1 at baseline; mean percentage change from baseline in PASI score; percentage of patients achieving ≥75% reduction from baseline in PASI score (PASI-75); percentage of patients achieving an absolute PASI score ≤3; mean percentage change from baseline in Nail Psoriasis Severity Index (NAPSI) score; and percentage of patients with nail psoriasis at baseline who achieved ≥50% reduction from baseline in NAPSI score (NAPSI-50) in the target nail. Patient satisfaction was assessed using the 11-item, patient-completed Treatment Satisfaction Questionnaire for Medication (TSQM), version II.16
Safety assessments were conducted at screening and weeks 0, 1, 4, 12, and 16 during the placebo-controlled period. Safety was evaluated based on vital signs, weight, waist circumference, adverse events (AEs), clinical laboratory assessments, and complete physical examinations. To better characterize diarrhea, patients reporting diarrhea or similar events (eg, frequent bowel movements, loose bowels) were asked whether they had experienced ≥2 watery/liquid stools in a day. Patients who responded “yes” were asked how often, on average, since their last visit had they experienced ≥2 watery/liquid stools in a day. Patients who responded “no” were not questioned further.
Efficacy assessments were conducted for the intent-to-treat (ITT) population, which included all randomized patients. Approximately 219 patients were planned to be randomized to yield ≥85% power to detect a 15% difference between apremilast and placebo in mean percentage change from baseline in PGAxBSA. For analysis of the primary end point and other continuous variables at week 16, an analysis of covariance model with treatment and site as a factor and baseline value as a covariate was used. The sPGA 0 or 1 response rates and other categorical variables at week 16 were compared using the Cochran-Mantel-Haenszel test. Last-observation-carried-forward methodology was used to impute missing efficacy measurements. The safety population included all patients who were randomized and received ≥1 dose of study drug. AEs were summarized using descriptive statistics. Statistical analyses were conducted using SAS version 9.2 (SAS Institute Inc, Cary, NC).
Disposition and Baseline Characteristics
A total of 221 patients were randomized and comprised the ITT population (placebo, n=73; apremilast, n=148); 185 (84%) completed the placebo-controlled phase (weeks 0 to 16;