斑块状银屑病中的 Deucravacitinib:POETYK PSO-1、PSO-2 和 LTE 3 期试验的 4 年安全性和疗效结果

April W. Armstrong, M. Lebwohl, Richard B Warren, H. Sofen, Akimchi Morita, Shinichi Imafuku, M. Ohtsuki, L. Spelman, T. Passeron, Kim A. Papp, Matthew J Colombo, John Vaile, E. Vritzali, K. Hoyt, C. Daamen, Subhashis Banerjee, B. Strober, Diamant Thaçi, Andrew Blauvelt
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Here, deucravacitinib safety and efficacy are reported through 4 years. \nMethods: PSO-1/PSO-2 randomized patients 1:2:1 to placebo, deucravacitinib 6 mg QD, or apremilast 30 mg BID. At Week 52, patients in the LTE received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients receiving ≥1 deucravacitinib dose. Exposure-adjusted incidence rate (EAIR) per 100 person-years (PY) was used to assess adverse events (AEs). Efficacy outcomes included PASI 75, PASI 90, and sPGA 0/1 and were analyzed using mNRI in LTE patients receiving continuous deucravacitinib from Day 1 of the parent trials. \nResults: 1519 patients received ≥1 deucravacitinib dose; cumulative exposure was 4392.8 PY. EAIRs/100 PY were decreased/comparable from the 1- to 4-year cumulative period, respectively: AEs (229.2, 131.7), serious AEs (5.7, 5.0), deaths (0.2, 0.3), discontinuation due to AEs (4.4, 2.2), herpes zoster (0.8, 0.6), malignancies (1.0, 0.9), MACE (0.3, 0.3), and venous thromboembolism (0.2, 0.1). 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引用次数: 0

摘要

简介Deucravacitinib是一种口服、选择性、异位TYK2抑制剂,已在美国、欧盟和其他国家获得批准,用于治疗接受系统治疗的中重度斑块状银屑病成人患者。在针对中重度斑块状银屑病的 POETYK PSO-1 和 PSO-2 三期试验中,Deucravacitinib 的疗效优于安慰剂和阿普司特。试验完成后,患者可参加正在进行的 POETYK 长期扩展(LTE)试验。在此,我们将报告 deucravacitinib 4 年来的安全性和疗效。研究方法PSO-1/PSO-2将患者按1:2:1的比例随机分配到安慰剂、6 mg QD的deucravacitinib或30 mg BID的apremilast。第52周,LTE患者接受开放标签的6 mg QD deucravacitinib治疗。对接受≥1个剂量 deucravacitinib 的患者进行了安全性评估。不良事件(AEs)的评估采用暴露调整发病率(EAIR)/100人年(PY)。疗效结果包括 PASI 75、PASI 90 和 sPGA 0/1,采用 mNRI 对从母体试验第 1 天开始连续接受德拉瓦替尼治疗的 LTE 患者进行分析。结果1519名患者接受了≥1次德拉瓦替尼剂量;累计暴露量为4392.8PY。从1年到4年的累积期来看,EAIRs/100PY分别下降/相当:AEs(229.2,131.7)、严重AEs(5.7,5.0)、死亡(0.2,0.3)、AEs导致的停药(4.4,2.2)、带状疱疹(0.8,0.6)、恶性肿瘤(1.0,0.9)、MACE(0.3,0.3)和静脉血栓栓塞(0.2,0.1)。在持续使用 deucravacitinib 治疗的情况下(n = 513),临床应答率从第 3 年开始保持不变(PASI 75,73.8% [95% CI,69.6,78.0];PASI 90,49.0% [95% CI,44.4,53.7];sPGA 0/1,55.2% [95% CI,50.5,59.9])到 mNRI 第 4 年(PASI 75,71.7% [95% CI,67.0,76.3];PASI 90,47.5% [95% CI,42.6,52.4];sPGA 0/1,57.2% [95% CI,52.1,62.2])。结论连续治疗4年后,Deucravacitinib显示出持久的疗效和与3年疗效一致的安全性,没有出现新的或长期的安全性信号。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Deucravacitinib in Plaque Psoriasis: 4-Year Safety and Efficacy Results From the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials
Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the phase 3 POETYK PSO-1 and PSO-2 trials in moderate to severe plaque psoriasis. Upon trial completion, patients could enroll in the ongoing POETYK long-term extension (LTE) trial. Here, deucravacitinib safety and efficacy are reported through 4 years. Methods: PSO-1/PSO-2 randomized patients 1:2:1 to placebo, deucravacitinib 6 mg QD, or apremilast 30 mg BID. At Week 52, patients in the LTE received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients receiving ≥1 deucravacitinib dose. Exposure-adjusted incidence rate (EAIR) per 100 person-years (PY) was used to assess adverse events (AEs). Efficacy outcomes included PASI 75, PASI 90, and sPGA 0/1 and were analyzed using mNRI in LTE patients receiving continuous deucravacitinib from Day 1 of the parent trials. Results: 1519 patients received ≥1 deucravacitinib dose; cumulative exposure was 4392.8 PY. EAIRs/100 PY were decreased/comparable from the 1- to 4-year cumulative period, respectively: AEs (229.2, 131.7), serious AEs (5.7, 5.0), deaths (0.2, 0.3), discontinuation due to AEs (4.4, 2.2), herpes zoster (0.8, 0.6), malignancies (1.0, 0.9), MACE (0.3, 0.3), and venous thromboembolism (0.2, 0.1). With continuous deucravacitinib treatment (n = 513), clinical response rates were maintained from Year 3 (PASI 75, 73.8% [95% CI, 69.6, 78.0]; PASI 90, 49.0% [95% CI, 44.4, 53.7]; sPGA 0/1, 55.2% [95% CI, 50.5, 59.9]) to Year 4 (PASI 75, 71.7% [95% CI, 67.0, 76.3]; PASI 90, 47.5% [95% CI, 42.6, 52.4]; sPGA 0/1, 57.2% [95% CI, 52.1, 62.2]) by mNRI. Conclusion: Deucravacitinib demonstrated durable efficacy with continuous treatment and a safety profile through 4 years consistent with that at 3 years, without new or long-term safety signals.
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