Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial

作者：Steven G. Kelsen, Ioana Agache, Weily Soong, Elliot Israel, Geoffrey Chupp, Dorothy Cheung, Wiebke Theess, Xiaoying Yang, Tracy Staton, David F. Choy, Alice Fong, Ajit Dash, Michael Dolton, Rajita Pappu, Christopher E. Brightling · 发表于：Journal of Allergy and Clinical Immunology · 年份：2021 · DOI：10.1016/j.jaci.2021.03.044 · 被引用次数：320 · 研究领域：IL-33, ST2, and ILC Pathways、Asthma and respiratory diseases、Eosinophilic Esophagitis

BACKGROUND: mAb, selectively inhibits the IL-33 receptor, ST2. Approved biologic therapies for severe asthma mainly benefit patients with elevated blood eosinophils (type 2-high), but limited options are available for patients with low blood eosinophils (type 2-low). Inhibiting IL-33 signaling may target pathogenic pathways in a wider spectrum of asthmatics. OBJECTIVES: This study evaluated astegolimab efficacy and safety in patients with severe asthma. METHODS: This double-blind, placebo-controlled, dose-ranging study (ZENYATTA [A Study to Assess the Efficacy and Safety of MSTT1041A in Participants With Uncontrolled Severe Asthma]) randomized 502 adults with severe asthma to subcutaneous placebo or 70-mg, 210-mg, or 490-mg doses of astegolimab every 4 weeks. The primary endpoint was the annualized asthma exacerbation rate (AER) at week 54. Enrollment caps ensured ∼30 patients who were eosinophil-high (≥300 cells/μL) and ∼95 patients who were eosinophil-low (<300 cells/μL) per arm. RESULTS: Overall, adjusted AER reductions relative to placebo were 43% (P = .005), 22% (P = .18), and 37% (P = .01) for 490-mg, 210-mg, and 70-mg doses of astegolimab, respectively. Adjusted AER reductions for patients who were eosinophil-low were comparable to reductions in the overall population: 54% (P = .002), 14% (P = .48), and 35% (P = .05) for 490-mg, 210-mg, and 70-mg doses of astegolimab. Adverse events were similar in astegolimab- and placebo-treated groups. CONCLUSIONS: Astegolimab reduc...