A Phase 2 Randomized Trial of Apremilast in Patients With Atopic Dermatitis

A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis (AD). Patients were randomized to placebo, apremilast 30 mg BID (APR30), or apremilast 40 mg BID (APR40) for 12 weeks. During Weeks 12–24, all patients received APR30 or APR40. A biopsy substudy evaluated AD-related biomarkers. Among 185 randomized intent-to-treat patients at Week 12, a dose-response relationship was observed; APR40 (n=63), but not APR30 (n=58), led to statistically significant improvements (vs. placebo [n=64]) in Eczema Area and Severity Index (mean [SD] percentage change from baseline: −31.6% [44.6] vs. −11.0% [71.2]; P<0.04; primary endpoint). mRNA expression of Th17/Th22-related markers (IL-17A, IL-22, S100A7/A8; P<0.05) showed the highest reductions with APR40, with minimal changes in other immune axes. Safety with APR30 was largely consistent with apremilast’s known profile (common adverse events [AEs]: nausea, diarrhea, headache, nasopharyngitis). With APR40, AEs were more frequent and cellulitis occurred (n=6). An independent safety monitoring committee discontinued the APR40 dose. APR40 demonstrated modest efficacy and decreased AD-related biomarkers in moderate to severe AD patients. AEs, including cellulitis, were more frequent with APR40, which was discontinued during the trial.