A Phase 2 Randomized Trial of Apremilast in Patients With Atopic Dermatitis. 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). Overall design: 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.

本项II期、双盲、安慰剂对照临床试验，评估了阿普斯特（apremilast）在中度至重度特应性皮炎（atopic dermatitis, AD）成人患者中的疗效、安全性与药效学特征。
试验总体设计如下：受试者被随机分配至安慰剂组、阿普斯特30mg每日两次（APR30）组或阿普斯特40mg每日两次（APR40）组，干预周期为12周。在第12至24周期间，所有受试者均接受APR30或APR40治疗。本试验设有活检亚研究，用于评估AD相关生物标志物。
在第12周时，纳入意向治疗分析的185例随机化受试者中观察到剂量-反应关系：与安慰剂组（n=64）相比，APR40组（n=63）的湿疹面积及严重程度指数（Eczema Area and Severity Index）实现了具有统计学意义的显著改善（基线百分比变化均值[标准差]：-31.6% [44.6] 对比 -11.0% [71.2]；P<0.04），该指标为本次试验的主要终点；而APR30组（n=58）未观察到显著改善。
Th17/Th22相关标志物（IL-17A、IL-22、S100A7/A8）的mRNA表达水平在APR40组中降幅最大，其他免疫通路的标志物仅出现微小变化。
APR30组的安全性特征整体与阿普斯特已知的安全性谱一致，常见不良事件（adverse events, AEs）包括恶心、腹泻、头痛、鼻咽炎。APR40组的不良事件发生率更高，且出现了蜂窝织炎病例（n=6），独立安全监测委员会因此终止了APR40剂量组的试验。
APR40在中度至重度AD患者中展现出中等程度的疗效，并可降低AD相关生物标志物水平；但APR40组的不良事件（包括蜂窝织炎）发生率更高，该剂量组在试验过程中被终止。