哥本哈根大学John Vissing研究组取得一项新突破。他们提出了依比利珠单抗治疗广泛性重症肌无力的3期临床试验。相关论文于2025年4月8日发表在《新英格兰医学杂志》上。

背景：自身免疫性全身性重症肌无力是一种表现为波动性肌无力的疾病。Inebilizumab是一种单克隆抗体，可消耗CD19+ B细胞，而CD19+ B细胞是疾病发病机制的核心。

方法：在这项3期、双盲、随机、安慰剂对照试验中，该课题组人员招募了患有重症肌无力的患者，他们有抗乙酰胆碱受体抗体或抗肌肉特异性激酶抗体。参与者以1:1的比例随机分配，接受静脉注射Inebilizumab（所有参与者在第1天和第15天给予300毫克，乙酰胆碱受体抗体阳性的参与者在第183天额外给予）或匹配安慰剂，为期52周（乙酰胆碱受体抗体阳性的参与者）或26周（肌肉特异性激酶抗体阳性的参与者）。糖皮质激素治疗逐渐减少，从第4周开始，到第24周达到每天5毫克的目标。主要终点是重症肌无力日常生活活动量表(MG-ADL；在第26周的联合乙酰胆碱受体抗体阳性和肌肉特异性激酶抗体阳性试验人群中，得分范围从0到24，得分越高表明疾病活动性越大。一个关键的次要终点是定量重症肌无力量表(QMG；在联合人群中，得分范围从0到39，得分越高表明疾病活动性越大)。评估了安全性。

结果：共有238名参与者接受随机分组（每组119人）。接受依比利珠单抗治疗的受试者的MG-ADL评分比接受安慰剂治疗的受试者有更大的降低(最小二乘平均变化，- 4.2 vs. - 2.2；调整差，1.9；95%置信区间为2.9 ~ 1.0；p < 0.001)，第26周。接受依比利珠单抗治疗的受试者比接受安慰剂治疗的受试者QMG评分降低更大(最小二乘平均变化，- 4.8 vs. - 2.3；调整差，2.5；95% CI, - 3.8 到- 1.2；p <0.001)。依比利珠单抗最常见的不良事件是头痛、咳嗽、鼻咽炎、输液相关反应和尿路感染。Inebilizumab与较高的严重不良事件发生率无关。

研究结果表明，在乙酰胆碱受体抗体阳性或肌肉特异性激酶抗体阳性的全身性重症肌无力患者中，Inebilizumab可改善功能并降低疾病严重程度。

附：英文原文

Title: A Phase 3 Trial of Inebilizumab in Generalized Myasthenia Gravis

Author: Richard J. Nowak, Michael Benatar, Emma Ciafaloni, James F. Howard, Jr., M. Isabel Leite, Kimiaki Utsugisawa, John Vissing, Mikhail Rojavin, Qing Li, Fengming Tang, Yanping Wu, Nishi Rampal, Sue Cheng

Issue&Volume: 2025-04-08

Abstract: BACKGROUND

Autoimmune generalized myasthenia gravis is a disease that manifests with fluctuating muscle weakness. Inebilizumab is a monoclonal antibody that depletes CD19+ B cells, which are central to disease pathogenesis.

METHODS

In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled participants with myasthenia gravis who had anti–acetylcholine receptor antibodies or anti–muscle-specific kinase antibodies. Participants were randomly assigned, in a 1:1 ratio, to receive intravenous inebilizumab (300 mg administered on days 1 and 15 for all, and additionally on day 183 for participants who were acetylcholine receptor antibody–positive) or matching placebo for 52 weeks (in participants who were acetylcholine receptor antibody–positive) or 26 weeks (in those who were muscle-specific kinase antibody–positive). Glucocorticoid therapy was tapered, starting at week 4, to a target of 5 mg per day by week 24. The primary end point was the change from baseline in the score on the Myasthenia Gravis Activities of Daily Living scale (MG-ADL; scores range from 0 to 24, with higher scores indicating greater disease activity) at week 26 in the combined acetylcholine receptor antibody–positive and muscle-specific kinase antibody–positive trial populations. A key secondary end point was the change from baseline in the score on the Quantitative Myasthenia Gravis scale (QMG; scores range from 0 to 39, with higher scores indicating greater disease activity) at week 26 in the combined population. Safety was assessed.

RESULTS

A total of 238 participants underwent randomization (119 per group). Participants who received inebilizumab had a greater reduction in the MG-ADL score than those who received placebo (least-squares mean change, 4.2 vs. 2.2; adjusted difference, 1.9; 95% confidence interval [CI], 2.9 to 1.0; P<0.001) at week 26. Participants who received inebilizumab had a greater reduction in the QMG score than those who received placebo (least-squares mean change, 4.8 vs. 2.3; adjusted difference, 2.5; 95% CI, 3.8 to 1.2; P<0.001). The most common adverse events with inebilizumab were headache, cough, nasopharyngitis, infusion-related reactions, and urinary tract infections. Inebilizumab was not associated with a higher incidence of serious adverse events.

CONCLUSIONS

In participants with acetylcholine receptor antibody–positive or muscle-specific kinase antibody–positive generalized myasthenia gravis, inebilizumab improved function and reduced disease severity.

DOI: NJ202504080000009

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2501561