作者
Chong Yan,Yao-Xian Yue,Yuzhou Guan,Bitao Bu,Qing Ke,Rui‐Sheng Duan,Hui Deng,Qun Xue,Huimin Jiang,Fei Xiao,Huan Yang,Ting Chang,Zhang‐Yu Zou,Haifeng Li,Song Tan,Huiling Xiao,Hongyu Zhou,Hua Zhang,Qiang Meng,Wenyu Li,Wei Li,Junhong Guo,Yali Zhang,Zunbo Li,Jiyuan Tu,Jianming Shi,Wei Li,Michael Lee,Yu. M. Chumakov,Xiaolu Tao,Shen Zhao,Ping Li,Chongbo Zhao,Jianying Xi,Chuanzhu Yan,Bin Zhang,Min Song,Rui Zheng,Xiaojun Ding,Chunqing Zhao,Yap‐Peng Tan,Jiayu Shi,Jianwen Wang,Xiaoli Li,Bing Yang,Min Zhang,Congcong Wang,Xu Wang,Xia Xiao,Xiaopei Ji,Hairong Zheng,Juhua Luo,Hao Zhou,Huanhuan Li,Zhe Ruan,Lidong Jiao,Lisa Hui,Jialin Chen,Sheng Chen,Hongbin Sun,Qingmin Zeng,Ying Xie,Kai Cui,Lingfeng Zeng,Wenshuang Zeng,Qin Du,Jian Yin,Shaozhen Hou,Lei Zhang,Mingming Zhao,Ruihan Yang,Wen Huang,Xiao Hu,Lei Jin,Yuying Zhao,Tao Dai,Wei Zhang,Xueli Chang,Xue Bai,Xiuyun Liu,Fu‐Jun Jia,Tao Xiong,Jiaojiao Ma,Hong-Dong Zhao,Meng Zhang,Jie Dong
摘要
Myasthenia gravis (MG) is caused by autoantibodies that disrupt the neuromuscular junction. The neonatal fragment crystallizable receptor (FcRn) antagonists, efgartigimod and rozanolixizumab, reduce immunoglobulin G (IgG) level in the circulation and alleviate symptoms in patients with generalized MG.To examine the efficacy and safety profile of batoclimab, a monoclonal IgG1 antibody, in patients with generalized MG.This was a multicenter randomized clinical trial conducted from September 15, 2021, to June 29, 2022, at 27 centers in China. Adult patients 18 years or older with generalized MG were screened, and those who were antibody positive were enrolled.Eligible patients received batoclimab or matching placebo in addition to standard of care. Each treatment cycle consisted of 6 weekly subcutaneous injections of batoclimab, 680 mg, or matching placebo followed by 4 weeks of observation. A second treatment cycle was conducted in patients who required continuing treatment.The primary outcome was sustained improvement, as defined by a 3-point or greater reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline for 4 or more consecutive weeks in the first cycle in individuals who were positive for acetylcholine receptor or muscle-specific kinase antibodies.A total of 178 adult patients with generalized MG were screened, 132 were randomly assigned, 131 tested positive for antibodies, and 1 tested negative for antibodies. A total of 132 patients (mean [SE] age, 43.8 [13.6] years; 88 women [67.2%]) were enrolled. The rate of sustained MG-ADL improvement in the first cycle in antibody-positive patients was 31.3% (20 of 64) in the placebo group vs 58.2% (39 of 67) in the batoclimab group (odds ratio, 3.45; 95% CI, 1.62-7.35; P = .001). The MG-ADL score diverged between the 2 groups as early as week 2. The mean (SE) maximum difference in MG-ADL score reduction occurred 1 week after the last dose (day 43, 1.7 [0.3] in the placebo group vs 3.6 [0.3] in the batoclimab group; group difference, -1.9; 95% CI, -2.8 to -1.0; nominal P < .001). The rates of treatment-related and severe treatment-emergent adverse events in patients were 36.9% (24 of 65) and 7.7% (5 of 65) in the placebo group vs 70.1% (47 of 67) and 3.0% (2 of 67) in the batoclimab group, respectively.Batoclimab increased the rate of sustained MG-ADL improvement and was well tolerated in adult patients with generalized MG. Clinical effects and the extent of IgG reduction were similar to those previously reported for efgartigimod and rozanolixizumab. Future studies of large sample size are needed to further understand the safety profile of batoclimab.ClinicalTrials.gov Identifier: NCT05039190.