Igarashi Dermatology Higashigotanda, Tokyo, Japan.
Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan.
J Dermatol. 2024 Oct;51(10):1269-1278. doi: 10.1111/1346-8138.17423. Epub 2024 Aug 16.
Tapinarof is a non-steroidal, topical, aryl hydrocarbon receptor agonist. We evaluated the efficacy and safety of tapinarof cream (1%) in Japanese patients aged ≥18 years with plaque psoriasis in two phase 3 trials, ZBA4-1 and ZBA4-2. ZBA4-1 (N = 158) consisted of a 12-week, double-blind, vehicle-controlled treatment period (period 1) and a 12-week extension treatment period (period 2). Patients were randomized 2:1 to tapinarof or vehicle in period 1; subsequently, all patients who were enrolled in period 2 received tapinarof. ZBA4-2 (N = 305) was a 52-week, open-label, uncontrolled trial in which all patients received tapinarof. In period 1 of ZBA4-1, the proportion of patients who achieved a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 12 (PGA treatment success, the primary endpoint) was 20.06% in the tapinarof group and 2.50% in the vehicle group (p = 0.0035). The proportion of patients with ≥75% improvement from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (PASI75 response, a key secondary endpoint) was 37.7% in the tapinarof group and 3.8% in the vehicle group (p < 0.0001). In ZBA4-2, PGA treatment success rate was 30.0% at week 12, 51.3% at week 24, and 56.3% at week 52, and PASI75 response rate was 50.4% at week 12, 77.5% at week 24, and 79.9% at week 52, indicating that efficacy responses improved over time and were maintained over 52 weeks. Across the two trials, most adverse events (AEs) were mild or moderate; common AEs included folliculitis and contact dermatitis. In summary, tapinarof cream (1%) was efficacious and generally safe for up to 52 weeks of treatment in Japanese patients with plaque psoriasis.
他卡西醇是一种非甾体类、局部用、芳基烃受体激动剂。我们在两项 3 期临床试验 ZBA4-1 和 ZBA4-2 中评估了他卡西醇乳膏（1%）在年龄≥18 岁的日本斑块状银屑病患者中的疗效和安全性。ZBA4-1（N=158）包括 12 周的双盲、安慰剂对照治疗期（第 1 期）和 12 周的扩展治疗期（第 2 期）。患者按 2:1 的比例随机分配至第 1 期的他卡西醇或安慰剂；随后，所有入组第 2 期的患者均接受他卡西醇治疗。ZBA4-2（N=305）是一项为期 52 周的开放性、非对照试验，所有患者均接受他卡西醇治疗。在 ZBA4-1 的第 1 期，治疗 12 周时，PGA 评分改善≥2 级且达到 PGA 评分 0（清除）或 1（几乎清除）的患者比例（主要终点 PGA 治疗成功）在他卡西醇组为 20.06%，安慰剂组为 2.50%（p=0.0035）。治疗 12 周时，PASI 评分改善≥75%的患者比例（关键次要终点 PASI75 应答）在他卡西醇组为 37.7%，安慰剂组为 3.8%（p<0.0001）。在 ZBA4-2 中，治疗 12 周时 PGA 治疗成功率为 30.0%，24 周时为 51.3%，52 周时为 56.3%，治疗 12 周时 PASI75 应答率为 50.4%，24 周时为 77.5%，52 周时为 79.9%，表明疗效应答随时间改善并在 52 周内保持。在两项试验中，大多数不良事件（AE）为轻度或中度；常见的 AE 包括毛囊炎和接触性皮炎。总之，他卡西醇乳膏（1%）在日本斑块状银屑病患者中治疗长达 52 周时是有效且通常安全的。
