apremilast reported significantly greater treatment satisfaction than patients receiving placebo.10 We describe the efficacy and safety of apremilast in the open-label apremilast treatment phase (weeks 16 to 52) of UNVEIL.
MATERIALS AND METHODS
Patient PopulationAdults aged ≥18 years with a diagnosis of chronic plaque psoriasis for ≥6 months were eligible.10 Patients were required to have moderate plaque psoriasis, defined as BSA involvement of 5% to 10% and sPGA score of 3 (moderate) on a 6-point scale (0 [clear], 1 [almost clear], 2 [mild], 3 [moderate], 4 [severe], 5 [very severe]). Patients were ineligible if they had prior exposure to systemic or biologic treatment for psoriasis, psoriatic arthritis, or any indication that could affect assessment of psoriasis, or inflammatory or dermatologic conditions, including forms of psoriasis other than plaque psoriasis (eg, erythrodermic, guttate, or generalized, inverse, or pustular psoriasis).Study Design and Treatment RegimenUNVEIL was a phase IV, randomized, double-blind, placebo-controlled, multicenter investigation in the United States (NCT02425826). The study design and methods of the 16-week, placebo-controlled phase of UNVEIL have been reported.10 Using a centralized interactive voice response system, eligible patients were randomized (2:1) to receive apremilast 30 mg twice daily (apremilast) or placebo. At week 16, patients randomized to placebo at baseline initiated open-label treatment with apremilast (placebo/apremilast) and patients randomized to apremilast at baseline continued active treatment (apremilast/apremilast) through week 52. The institutional review boards of participating investigation sites approved the protocol, and all patients provided written informed consent before the conduct of any study-related procedures.10AssessmentsThe primary efficacy end point was mean percentage change from baseline in PGAxBSA score at week 16. The PGAxBSA is a validated tool11 that is simpler to use than the Psoriasis Area and Severity Index (PASI) for calculating disease severity and may be more likely to differentiate among patients with lower disease severity than the PASI.12 PGAxBSA was evaluated at scheduled time points throughout the open-label apremilast treatment phase, including week 52. Clinical assessments of psoriasis-involved BSA and sPGA were previously described.10End points evaluated at week 52 using the sPGA and BSA assessments included mean percentage change from baseline in PGAxBSA, achievement of ≥75% reduction from baseline in PGAxBSA (PGAxBSA-75), and achievement of sPGA response, defined as a score of 0 (clear) or 1 (almost clear). Other efficacy end points at week 52 included 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 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 (0 to 100 mm); 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; among patients with nail psoriasis at baseline, mean percentage change from baseline in Nail Psoriasis Severity Index (NAPSI) score and percentage of patients achieving ≥50% reduction from baseline in NAPSI score (NAPSI-50) in the target nail. Quality of life was assessed with the Dermatology Life Quality Index (DLQI); end points included mean change from baseline in DLQI total score and percentage of patients with baseline DLQI score >5 who achieved a minimal clinically important difference (MCID) on the DLQI, defined as a decrease from baseline ≥5 points. Patient satisfaction was assessed using the 11-item, patient-completed Treatment Satisfaction Questionnaire for Medication (TSQM), version II.13 Safety was evaluated based on adverse events (AEs) and other standard assessments previously described.10Statistical AnalysisStatistical analyses performed for the placebo-controlled phase, including the primary end point, have been reported.10 In the extension portion of the study reported here, efficacy was examined over 52 weeks using the intent-to-treat population established during the placebo-controlled phase and data from all patients who entered the open-label apremilast treatment phase (weeks 16 to 52). Data for 52-week analyses were summarized descriptively by treatment assignment from the randomized, double-blind phase (ie, placebo/apremilast and apremilast/apremilast groups). Last-observation-carried-forward methodology was used to impute missing efficacy measurements. Safety data were summarized descriptively for the 52-week apremilast-exposure period for patients who received ≥1 dose of apremilast, regardless of when apremilast was initiated (week 0 or week 16).
Disposition and Baseline CharacteristicsA total of 221 patients were initially enrolled and randomized (placebo, n=73; apremilast, n=148)10; 185 (84%) completed the placebo-controlled phase (weeks 0 to 16) and entered the open-label apremilast treatment phase (Figure 1). There were 136 (74%) patients who completed the 52-week analysis period, including 50/64 (78%) patients initially randomized to placebo and 86/121 (71%) initially randomized to apremilast.Baseline demographics and disease characteristics, based on the ITT population, were comparable between treatment groups, as previously reported.10 At baseline, mean duration of psoriasis was 13.9 and 17.5 years in the placebo and apremilast