Importance Use of biologic agents in generalized myasthenia gravis is generally limited to therapy-refractory cases; benefit in new-onset disease is unknown.

Objective To assess rituximab in refractory and new-onset generalized myasthenia gravis and rituximab vs conventional immunotherapy in new-onset disease.

Design, Setting, and Participants A retrospective cohort study with prospectively collected data was conducted on a county-based community sample at Karolinska University Hospital, Stockholm, Sweden. Participants included 72 patients with myasthenia gravis, excluding those displaying muscle-specific tyrosine kinase antibodies, initiating rituximab treatment from January 1, 2010, to December 31, 2018, and patients with new-onset disease initiating conventional immunotherapy from January 1, 2003, to December 31, 2012, with 12 months or more of observation time. The present study was conducted from March 1, 2019, to January 31, 2020.

Exposures Treatment with low-dose rituximab (most often 500 mg every 6 months) or conventional immunosuppressants.

Main Outcomes and Measures Time to remission (main outcome) as well as use of rescue therapies or additional immunotherapies and time in remission (secondary outcomes).

Results Of the 72 patients included, 31 patients (43%) were women; mean (SD) age at treatment start was 60 (18) years. Twenty-four patients had received rituximab within 12 months of disease onset and 48 received rituximab at a later time, 34 of whom had therapy-refractory disease. A total of 26 patients (3 [12%] women; mean [SD] age, 68 [11] years at treatment start) received conventional immunosuppressant therapy. Median time to remission was shorter for new-onset vs refractory disease (7 vs 16 months: hazard ratio [HR], 2.53; 95% CI, 1.26-5.07; P = .009 after adjustment for age, sex, and disease severity) and for rituximab vs conventional immunosuppressant therapies (7 vs 11 months: HR, 2.97; 95% CI, 1.43-6.18; P = .004 after adjustment). In addition, fewer rescue therapy episodes during the first 24 months were required (mean [SD], 0.38 [1.10] vs 1.31 [1.59] times; mean difference, −1.26; 95% CI, −1.97 to −0.56; P < .001 after adjustment), and a larger proportion of patients had minimal or no need of additional immunotherapies (70% vs 35%; OR, 5.47; 95% CI, 1.40-21.43; P = .02 after adjustment). Rates of treatment discontinuation due to adverse events were lower with rituximab compared with conventional therapies (3% vs 46%; P < .001 after adjustment).

Conclusions and Relevance Clinical outcomes with rituximab appeared to be more favorable in new-onset generalized myasthenia gravis, and rituximab also appeared to perform better than conventional immunosuppressant therapy. These findings suggest a relatively greater benefit of rituximab earlier in the disease course. A placebo-controlled randomized trial to corroborate these findings is warranted.

重要性 广义重症生物制剂使用肌无力一般仅限于治疗难治性病例; 新发疾病的获益尚不清楚。

目的 评估利妥昔单抗在难治性和新发的广义重症肌无力和利妥昔单抗与常规免疫治疗中的关系。

设计，设置和参与者 在瑞典斯德哥尔摩的卡罗林斯卡大学医院，对一个县级社区样本进行了回顾性队列研究，收集了前瞻性收集的数据。参与者包括72例重症肌无力患者，不包括展示肌肉特异性酪氨酸激酶抗体的患者，这些患者从2010年1月1日至2018年12月31日开始使用利妥昔单抗治疗，以及新疾病患​​者从2003年1月1日开始进行常规免疫治疗。 2012年12月31日，观察时间为12个月或更长时间。本研究于2019年3月1日至2020年1月31日进行。

低剂量利妥昔单抗（最常见的是每6个月500 mg）或常规免疫抑制剂进行暴露治疗。

主要结果和衡量指标 缓解时间（主要结果）以及使用抢救疗法或其他免疫疗法的时间和缓解时间（次要结果）。

结果 纳入的72例患者中，有31例（43％）为女性。治疗开始时的平均（SD）年龄为60（18）岁。24名患者在发病后12个月内接受了利妥昔单抗治疗，48位患者在以后的时间接受了利妥昔单抗治疗，其中34例患有难治性疾病。共有26名患者（3名[12％]妇女；平均[SD]年龄，开始治疗时为68 [11]岁）接受了常规的免疫抑制剂治疗。新发与顽固性疾病的中位缓解时间较短（7 vs 16个月：危险比[HR]，2.53； 95％CI，1.26-5.07； 根据年龄，性别和疾病严重程度进行调整后，P = .009 ）以及利妥昔单抗与常规免疫抑制剂治疗的比较（7个月与11个月：HR，2.97； 95％CI，1.43-6.18；P = .004（调整后）。此外，在头24个月内需要的抢救治疗次数较少（平均[SD]为0.38 [1.10]比1.31 [1.59]倍；平均差异为-1.26； 95％CI为-1.97至-0.56；P  <。调整后为001），并且更大比例的患者很少或不需要额外的免疫疗法（70％vs 35％； OR为5.47； 95％CI为1.40-21.43；P  = 0.02）。与传统疗法相比，利妥昔单抗因不良事件导致的治疗中止率更低（3％比46％；P  <.001调整后）。

结论与相关性 利妥昔单抗的临床结局在新发的广义重症肌无力中似乎更为有利，并且利妥昔单抗的疗效似乎也优于传统的免疫抑制剂。这些发现表明，在疾病过程的早期，利妥昔单抗具有相对更大的益处。有必要进行安慰剂对照的随机试验以证实这些发现。