Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis

作者：April W. Armstrong, Melinda Gooderham, Charles Lynde, Catherine Maari, Seth Forman, Lawrence Green, Vivian Laquer, Xinyan Zhang, Nathalie Franchimont, Esha Gangolli, Jessamyn Blau, Yiwei Zhao, Wenwen Zhang, Bhaskar Srivastava, Graham Heap, Kim Papp · 发表于：JAMA Dermatology · 年份：2024 · DOI：10.1001/jamadermatol.2024.2701 · 被引用次数：47 · 研究领域：Psoriasis: Treatment and Pathogenesis、Spondyloarthritis Studies and Treatments、Cytokine Signaling Pathways and Interactions

Importance: 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. Objective: 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. Intervention: 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. Main Outcomes and Measures: 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. Results: In total, 259 patients were randomized and received treatment (mean [...