University of California, Los Angeles.
SKiN Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, Canada.
JAMA Dermatol. 2024 Oct 1;160(10):1066-1074. doi: 10.1001/jamadermatol.2024.2701.
New, effective, and well-tolerated oral therapies are needed for treating psoriasis. Zasocitinib, a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is a potential new oral treatment for this disease.
To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2b, randomized, double-blind, placebo-controlled, multiple-dose randomized clinical trial was conducted from August 11, 2021, to September 12, 2022, at 47 centers in the US and 8 in Canada. The study included a 12-week treatment period and a 4-week follow-up period. Key eligibility criteria for participants included age 18 to 70 years; a Psoriasis Area and Severity Index (PASI) score of 12 or greater; a Physician's Global Assessment score of 3 or greater; and a body surface area covered by plaque psoriasis of 10% or greater. Of 287 patients randomized, 259 (90.2%) received at least 1 dose of study treatment.
Patients were randomly assigned (1:1:1:1:1) to receive zasocitinib at 2, 5, 15, or 30 mg or placebo orally, once daily, for 12 weeks.
The primary efficacy end point was the proportion of patients achieving 75% or greater improvement in PASI score (PASI 75) at week 12. Secondary efficacy end points included PASI 90 and 100 responses. Safety was also assessed.
In total, 259 patients were randomized and received treatment (mean [SD] age, 47 [13] years; 82 women [32%]). At week 12, PASI 75 was achieved for 9 (18%), 23 (44%), 36 (68%), and 35 (67%) patients receiving zasocitinib at 2, 5, 15, and 30 mg, respectively, and 3 patients (6%) receiving placebo. PASI 90 responses were consistent with PASI 75. PASI 100 demonstrated a dose response at all doses, with 17 patients (33%) achieving PASI 100 with zasocitinib, 30 mg. Treatment-emergent adverse events occurred for 23 patients (44%) receiving placebo and 28 (53%) to 31 (62%) patients receiving the 4 different doses of zasocitinib, with no dose dependency and no clinically meaningful longitudinal differences in laboratory parameters.
This randomized clinical trial found that potent and selective inhibition of TYK2 with zasocitinib at oral doses of 5 mg or more once daily resulted in greater skin clearance than placebo over 12 weeks.
ClinicalTrials.gov Identifier: NCT04999839.
需要新的、有效的和耐受良好的口服疗法来治疗银屑病。扎索替尼是一种高度选择性的别构酪氨酸激酶 2（TYK2）抑制剂，是治疗这种疾病的一种潜在新的口服疗法。
评估扎索替尼在中重度斑块状银屑病患者中的疗效、安全性和耐受性。
设计、地点和参与者：这是一项 2b 期、随机、双盲、安慰剂对照、多剂量随机临床试验，于 2021 年 8 月 11 日至 2022 年 9 月 12 日在美国 47 个中心和加拿大 8 个中心进行。研究包括 12 周的治疗期和 4 周的随访期。参与者的主要入选标准包括年龄 18 至 70 岁；银屑病面积和严重程度指数（PASI）评分≥12；医生整体评估评分≥3；斑块状银屑病覆盖的体表面积≥10%。在 287 名随机患者中，259 名（90.2%）至少接受了 1 次研究治疗。
患者随机（1:1:1:1:1）接受扎索替尼 2、5、15 或 30mg 或安慰剂，每日 1 次，口服，共 12 周。
主要疗效终点是在第 12 周时 PASI 评分改善≥75%（PASI 75）的患者比例。次要疗效终点包括 PASI 90 和 100 反应。同时还评估了安全性。
共 259 名患者随机接受治疗（平均[SD]年龄 47[13]岁；82 名女性[32%]）。在第 12 周，接受扎索替尼 2、5、15 和 30mg 治疗的患者分别有 9 名（18%）、23 名（44%）、36 名（68%）和 35 名（67%）达到 PASI 75，而接受安慰剂治疗的患者有 3 名（6%）。PASI 90 反应与 PASI 75 一致。PASI 100 显示出剂量反应，所有剂量的扎索替尼治疗均有 17 名患者（33%）达到 PASI 100，其中 30mg 剂量有 3 名患者（6%）达到 PASI 100。接受安慰剂治疗的 23 名患者（44%）和接受扎索替尼 4 种不同剂量治疗的 28 名（53%）至 31 名（62%）患者发生了治疗出现的不良事件，没有剂量依赖性，也没有实验室参数的临床意义上的纵向差异。
这项随机临床试验发现，与安慰剂相比，每日口服剂量为 5mg 或以上的 TYK2 强效和选择性抑制扎索替尼在 12 周内可使皮肤清除率更高。
ClinicalTrials.gov 标识符：NCT04999839。
