Probity Medical Research, Waterloo, ON, Canada Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany Celgene Corporation, Summit, NJ, USA.
J Eur Acad Dermatol Venereol. 2013 Mar;27(3):e376-83. doi: 10.1111/j.1468-3083.2012.04716.x. Epub 2012 Oct 3.
Apremilast, a small molecule specific inhibitor of phosphodiesterase 4, works intracellularly to modulate pro-inflammatory and anti-inflammatory mediator production.
Assess apremilast efficacy and safety in moderate to severe plaque psoriasis.
Phase II, 12-week, multicenter, double-blind, placebo-controlled, parallel-group, dose-comparison study of 259 subjects randomized 1 : 1 : 1 to placebo, apremilast 20 mg QD or apremilast 20 mg BID.
More subjects receiving apremilast 20 mg BID achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI-75) vs. placebo (24.4% vs. 10.3%; P = 0.023). A similar proportion of subjects receiving apremilast 20 mg QD and placebo achieved PASI-75 at week 12 [9/87 (10.3%, each group)]. Mean per cent reduction in PASI from baseline was 17.4% for placebo, 30.3% for apremilast 20 mg QD (P = 0.021 vs. placebo) and 52.1% for apremilast 20 mg BID (P < 0.001). Apremilast 20 mg BID significantly decreased mean body surface area involvement vs. placebo (30.8% vs. 3.2%; P < 0.001). The most common adverse events were headache, nasopharyngitis, diarrhoea and nausea. Most events (> 90%) were mild to moderate and did not lead to study discontinuation. Serious adverse events occurred in four placebo subjects (panic attack, hospitalization for rehabilitation, hospitalization for alcoholism, worsening psoriasis), one receiving apremilast 20 mg QD (knee surgery) and in one receiving apremilast 20 mg BID (worsening psoriasis). The panic attack was considered treatment-related; both cases of worsening psoriasis occurred after medication discontinuation. No deaths or opportunistic infections were reported.
Apremilast 20 mg BID for 12 weeks was effective and well tolerated in subjects with moderate to severe plaque psoriasis.
磷酸二酯酶 4 的小分子特异性抑制剂阿普司特在细胞内起作用，调节促炎和抗炎介质的产生。
评估阿普司特治疗中度至重度斑块状银屑病的疗效和安全性。
这是一项为期 12 周的、多中心、双盲、安慰剂对照、平行组、剂量比较的 259 例受试者的 2 期研究，这些受试者按 1:1:1 的比例随机分为安慰剂组、阿普司特 20mgQD 组或阿普司特 20mgBID 组。
与安慰剂相比，接受阿普司特 20mgBID 治疗的受试者中达到银屑病面积和严重程度指数（PASI75）改善≥75%的比例更高（24.4%比 10.3%；P=0.023）。接受阿普司特 20mgQD 和安慰剂治疗的受试者在第 12 周达到 PASI75 的比例相似[9/87（10.3%，每组）]。与安慰剂相比，阿普司特 20mgQD 和阿普司特 20mgBID 治疗组的 PASI 基线平均百分比降低分别为 17.4%和 30.3%（P=0.021 与安慰剂）和 52.1%（P<0.001）。与安慰剂相比，阿普司特 20mgBID 显著降低了平均体表面积受累（30.8%比 3.2%；P<0.001）。最常见的不良反应是头痛、鼻咽炎、腹泻和恶心。大多数事件（>90%）为轻至中度，且未导致研究中止。4 例安慰剂受试者（惊恐发作、康复住院、酒精中毒住院、银屑病恶化）、1 例接受阿普司特 20mgQD 治疗的受试者（膝关节手术）和 1 例接受阿普司特 20mgBID 治疗的受试者（银屑病恶化）发生了严重不良事件。惊恐发作被认为与治疗相关；在停止药物治疗后，均出现银屑病恶化。未报告死亡或机会性感染。
在中重度斑块状银屑病患者中，阿普司特 20mgBID 治疗 12 周是有效且耐受良好的。
