Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, UK.
Br J Dermatol. 2024 Apr 17;190(5):668-679. doi: 10.1093/bjd/ljae014.
BACKGROUND: In the phase III POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, was well tolerated and efficacious over 1 year in patients with psoriasis. OBJECTIVE: To evaluate deucravacitinib safety and efficacy over 2 years in patients participating in the phase III trials. METHODS: In the POETYK long-term extension (LTE), an ongoing phase IIIb open-label trial, adults with moderate-to-severe plaque psoriasis who completed PSO-1 or PSO-2 receive deucravacitinib 6 mg once daily. Safety was assessed via adverse events (AEs) and laboratory parameter abnormalities. Efficacy endpoints, including ≥ 75% reduction from baseline Psoriasis Area and Severity Index score (PASI 75) and static Physician's Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients who crossed over from placebo at week 16 and patients who achieved PASI 75 at week 24 (peak efficacy). RESULTS: At data cutoff (1 October 2021), 1519 patients had received at least one dose of deucravacitinib; 79.0% and 39.9% had ≥ 52 weeks and ≥ 104 weeks of total deucravacitinib exposure, respectively. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were similar at 1 year and 2 years for any AEs (229.2 vs. 154.4, respectively), serious AEs (5.7 vs. 6.1), discontinuations (4.4 vs. 2.8), deaths (0.2 vs. 0.4), serious infections (1.7 vs. 2.6), herpes zoster (0.9 vs. 0.8), major adverse cardiovascular events (0.3 vs. 0.4), venous thromboembolic events (0.2 vs. 0.1) and malignancies (1.0 vs. 0.9). EAIRs for COVID-19 infections were higher at 2 years than at 1 year (5.1 vs. 0.5) owing to the peak of the global COVID-19 pandemic occurring during the LTE. No clinically meaningful changes from baseline or trends were observed over 2 years in haematological, chemistry or lipid parameters. Clinical responses were maintained in patients who received continuous deu-cravacitinib treatment from baseline [PASI 75: week 52, 72.4%; week 112, 79.7%; sPGA 0/1: week 52, 57.9%; week 112, 61.1% (as observed)]. Responses at week 52 were also maintained in placebo crossovers and in week-24 PASI-75 responders. CONCLUSIONS: Deucravacitinib maintained efficacy and demonstrated consistent safety with no new safety signals observed through 2 years.
背景：在 III 期 POETYK PSO-1 和 PSO-2 试验中，口服选择性别构酪氨酸激酶 2 抑制剂德瓦鲁单抗在银屑病患者中经过 1 年的治疗，具有良好的耐受性和疗效。 目的：评估 III 期试验中参加者使用德瓦鲁单抗的 2 年安全性和疗效。 方法：在 POETYK 长期扩展（LTE）试验中，正在进行的 IIIb 期开放标签试验中，完成 PSO-1 或 PSO-2 的中重度斑块型银屑病成年患者接受德瓦鲁单抗 6mg 每日一次治疗。通过不良反应（AE）和实验室参数异常来评估安全性。在最初随机接受德瓦鲁单抗的患者、在第 16 周时交叉至安慰剂的患者和在第 24 周时达到 PASI75 的患者（峰值疗效）中评估疗效终点，包括从基线 PSORASI 评分降低≥75%（PASI75）和静态医师总体评估（sPGA）评分 0/1（清除/几乎清除）。 结果：在数据截止（2021 年 10 月 1 日）时，1519 名患者至少接受了一剂德瓦鲁单抗；79.0%和 39.9%患者的德瓦鲁单抗总暴露时间分别≥52 周和≥104 周。任何 AE（229.2 比 154.4）、严重 AE（5.7 比 6.1）、停药（4.4 比 2.8）、死亡（0.2 比 0.4）、严重感染（1.7 比 2.6）、带状疱疹（0.9 比 0.8）、主要不良心血管事件（0.3 比 0.4）、静脉血栓栓塞事件（0.2 比 0.1）和恶性肿瘤（1.0 比 0.9）的发生率，在 1 年和 2 年时的调整发生率（EAIR）相似。由于全球 COVID-19 大流行的高峰期发生在 LTE 期间，因此 2 年时 COVID-19 感染的 EAIR 高于 1 年（5.1 比 0.5）。在 2 年期间，未观察到基线或趋势有任何具有临床意义的血液学、化学或脂质参数变化。从基线开始接受连续德瓦鲁单抗治疗的患者中，临床应答得到维持[PASI75：第 52 周，72.4%；第 112 周，79.7%；sPGA0/1：第 52 周，57.9%；第 112 周，61.1%（实际观察）]。在第 52 周时，安慰剂交叉患者和第 24 周时达到 PASI75 的患者也保持了应答。 结论：德瓦鲁单抗在 2 年期间保持了疗效，并表现出一致的安全性，未发现新的安全性信号。
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