Stapokibart for moderate-to-severe seasonal allergic rhinitis: a randomized phase 3 trial

作者：Yuan Zhang, Jingyun Li, Menglin Wang, Li Xian, Bing Yan, Jixiang Liu, Shi Li, Zhiwei Cao, Feng Yan, Weiwei Liu, Zhendong Xu, Ruixia Ma, Xiaoping Gao, Wenwen Liu, Jinmei Xue, Xiaoyong Ren, Xuezhong Li, Xicheng Song, Yi Yang, Yusheng Wang, Zhimin Xing, Fang Quan, Jing Pan, Yue Sun, Fengpo Shi, Xiaoqiu Chen, Hongyue Yan, Guoqing Zhao, Bo Chen, Chengshuo Wang, Luo Zhang · 发表于：Nature Medicine · 年份：2025 · DOI：10.1038/s41591-025-03651-5 · 被引用次数：43 · 研究领域：Allergic Rhinitis and Sensitization、Asthma and respiratory diseases、Respiratory and Cough-Related Research

Seasonal allergic rhinitis (SAR) places a significant socioeconomic burden, particularly on individuals with poorly managed recurrent and severe symptoms despite standard-of-care treatment. Stapokibart, a humanized monoclonal antibody that targets the interleukin (IL)-4 receptor subunit alpha, inhibits its interaction with both IL-4 and IL-13 in type 2 inflammation. Here we aim to assess the efficacy and safety of stapokibart as an add-on therapy in adults with moderate-to-severe SAR. The study was a phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial with 108 patients diagnosed with moderate-to-severe SAR and having baseline blood eosinophil counts ≥300 cells μl−1. Participants were randomized (1:1) to receive 600 mg (loading dose) to 300 mg stapokibart subcutaneously or a placebo every 2 weeks for 4 weeks. The primary endpoint was mean change from baseline in daily reflective total nasal symptom score (rTNSS) over the first 2 weeks. Multiplicity-tested secondary endpoints included changes in rTNSS over 4 weeks, reflective total ocular symptom score and Rhinoconjunctivitis Quality of Life Questionnaire score over 2 weeks and 4 weeks. Compared with the placebo, stapokibart led to a significant improvement in the mean change from baseline in daily rTNSS during the 2-week (least-squares mean difference, −1.3; 95% confidence interval, −2.0 to −0.6; P = 0.0008) and 4-week (least-squares mean difference, −1.7; 95% confidence interval, −2.5 to −0.8; P =...