Morita Akimichi, Imafuku Shinichi, Tada Yayoi, Okubo Yukari, Habiro Katsuyoshi, Tsuritani Katsuki, Banerjee Subhashis, Hoyt Kim, Kisa Renata M, Ohtsuki Mamitaro
Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Fukuoka University Faculty of Medicine, Fukuoka, Japan.
J Dermatol. 2025 May;52(5):761-772. doi: 10.1111/1346-8138.17685. Epub 2025 Mar 11.
Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, was effective and well tolerated at a dose of 6 mg once daily through 1 year (52 weeks) in patients with moderate to severe plaque psoriasis in the phase 3 POETYK PSO-1 and POETYK PSO-4 trials. Patients completing PSO-1 or PSO-4 could enter the ongoing POETYK long-term extension trial and receive open-label deucravacitinib. Safety and efficacy were evaluated through 3 years (148 weeks; data cutoff date: June 15, 2022) in Japanese patients in these trials. Safety was assessed via adverse events (AEs). Efficacy endpoints, including ≥75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients receiving continuous deucravacitinib treatment from baseline in PSO-1 and PSO-4 and in PSO-1 patients crossing over from placebo to deucravacitinib at week 16. At data cutoff, 125 patients had received at least one deucravacitinib dose; 86.4% had >24 months and 27.2% had >36 months of total deucravacitinib exposure. Exposure-adjusted incidence rates per 100 person-years for AEs were: any AEs, 188.5; discontinuations attributable to AEs, 3.2; serious AEs, 7.4; serious infections, 1.3; herpes zoster events, 1.6; major adverse cardiovascular events, 0.6; venous thromboembolic events, 0; and malignancies, 1.0. Clinical responses (as observed) were maintained in PSO-1 patients receiving continuous deucravacitinib treatment from baseline (PASI 75: year 1, 88.9%; year 3, 87.5%; sPGA 0/1: year 1, 74.1%; year 3, 66.7%). Year 1 response rates were also maintained through year 3 in PSO-4 patients and in PSO-1 placebo crossovers. Response rates were also consistent using modified nonresponder imputation and treatment failure rules data imputation methodologies. These findings support the consistent safety profile and durable efficacy of deucravacitinib through 3 years in Japanese patients with psoriasis. ClinicalTrials.gov: NCT03624127; NCT03924427; NCT04036435.
在3期POETYK PSO - 1和POETYK PSO - 4试验中，口服、选择性、变构酪氨酸激酶2抑制剂氘可来昔替尼，对于中度至重度斑块状银屑病患者，剂量为每日一次6毫克，持续1年（52周），疗效显著且耐受性良好。完成PSO - 1或PSO - 4试验的患者可进入正在进行的POETYK长期扩展试验，并接受开放标签的氘可来昔替尼治疗。在这些试验中，对日本患者的安全性和疗效进行了3年（148周；数据截止日期：2022年6月15日）的评估。通过不良事件（AE）评估安全性。在PSO - 1和PSO - 4试验中，从基线开始接受持续氘可来昔替尼治疗的患者，以及在第16周从安慰剂交叉至氘可来昔替尼治疗的PSO - 1患者中，评估疗效终点，包括银屑病面积和严重程度指数（PASI 75）较基线降低≥75%，以及静态医师整体评估（sPGA）评分为0/1（清除/几乎清除）。在数据截止时，125名患者至少接受过一剂氘可来昔替尼治疗；86.4%的患者总氘可来昔替尼暴露时间>24个月，27.2%的患者>36个月。每100人年不良事件的暴露调整发病率为：任何不良事件，188.5；因不良事件停药，3.2；严重不良事件，7.4；严重感染，1.3；带状疱疹事件，1.6；主要不良心血管事件，0.6；静脉血栓栓塞事件，0；恶性肿瘤，1.0。在PSO - 1试验中，从基线开始接受持续氘可来昔替尼治疗的患者中，临床反应（观察到的）得以维持（PASI 75：第1年，88.9%；第3年，87.5%；sPGA 0/1：第1年，74.1%；第3年，66.7%）。在PSO - 4试验患者和PSO - 1安慰剂交叉患者中，第1年的反应率在第3年也得以维持。使用改良的无反应者插补法和治疗失败规则数据插补方法时，反应率也保持一致。这些发现支持了氘可来昔替尼在日本银屑病患者中3年的一致安全性和持久疗效。ClinicalTrials.gov：NCT03624127；NCT03924427；NCT04036435。
