To determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR-Ab+ gMG).

The B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase 2 trial that utilized a futility design. Individuals 21–90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II–IV) and receiving prednisone ≥15 mg/d were eligible. The primary outcome was a measure of steroid-sparing effect, defined as the proportion achieving ≥75% reduction in mean daily prednisone dose in the 4-weeks prior to week 52 and with clinical improvement or no significant worsening as compared to the 4-week period prior to randomization. The coprimary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to a 2-cycle rituximab/placebo regimen, with follow-up through 52 weeks.

Of the 52 participants included, mean ± SD age at enrollment was 55.1 ± 17.1 years; 23 (44.2%) were women and 31 (59.6%) were Myasthenia Gravis Foundation of America Class II. The mean ± SD baseline prednisone dose was 22.1 ± 9.7 mg/d. The primary steroid-sparing outcome was achieved in 60% of those on rituximab vs 56% on placebo. The study reached its futility endpoint (p = 0.03), suggesting that the predefined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues were identified.

Although rituximab was safe and well-tolerated, these results suggest that there is a low probability of observing the defined clinically meaningful steroid-sparing effect over a 12-month period in a phase 3 trial of mild to moderately symptomatic AChR-Ab+ gMG.

This study provides Class I evidence that for mild to moderate AChR-Ab+ gMG, compared with placebo, rituximab is safe but unlikely to reduce steroid use by an absolute difference of at least 30% at 1 year.

ClinicalTrials.gov identifier: NCT02110706.

为了确定利妥昔单抗是否安全且可能有益，需要在乙酰胆碱受体抗体阳性全身性重症肌无力 (AChR-Ab+ gMG) 的疗效试验中进一步研究。

重症肌无力的 B 细胞靶向治疗 (BeatMG) 研究是一项随机、双盲、安慰剂对照、多中心 2 期试验，采用了无效设计。 21-90 岁、AChR-Ab+ gMG（美国 MG 基金会 II-IV 级）且接受泼尼松≥15 mg/d 的个体符合资格。主要结局是类固醇节约效应的衡量标准，定义为在第 52 周之前的 4 周内，每日平均泼尼松剂量减少 ≥75% 且与 4 周相比临床改善或没有显着恶化的比例随机化之前的一段时间。共同主要结果是安全性。次要结局包括 MG 特异性临床评估。 52 名受试者被随机 (1:1) 接受 2 个周期的利妥昔单抗/安慰剂治疗方案，并随访 52 周。

在纳入的 52 名参与者中，入组时的平均±标准差年龄为 55.1±17.1 岁； 23 名 (44.2%) 为女性，31 名 (59.6%) 为美国重症肌无力基金会 II 级。泼尼松基线剂量的平均值±标准差为 22.1 ± 9.7 mg/d。利妥昔单抗组中 60% 的患者实现了主要类固醇节约结果，而安慰剂组中这一比例为 56%。该研究达到了无效终点（ p = 0.03），这表明利妥昔单抗相对于安慰剂带来的 30% 的预定临床意义改善不太可能在随后的更大规模试验中实现。没有发现安全问题。

尽管利妥昔单抗是安全且耐受性良好的，但这些结果表明，在轻度至中度症状的 AChR-Ab+ gMG 的 3 期试验中，在 12 个月的时间内观察到明确的具有临床意义的类固醇节约效应的可能性较低。

这项研究提供了 I 类证据，表明对于轻度至中度 AChR-Ab+ gMG，与安慰剂相比，利妥昔单抗是安全的，但不太可能在 1 年时以至少 30% 的绝对差异减少类固醇的使用。

ClinicalTrials.gov 标识符：NCT02110706。