摘要：

目的 评价利妥昔单抗治疗难治性重症肌无力的有效性和安全性。方法 以rituximab、myasthenia gravis 等英文检索词计算机检索2000 年1 月1 日-2018 年4 月30 日美国国立医学图书馆生物医学信息检索系统（PubMed）、荷兰医学文摘（EMBASE/SCOPUS）、Cochrane 图书馆，并辅助手工检索获得回顾性病例分析和病例观察研究，采用Newcastle-Ottawa量表和Stata 12.0统计软件进行文献质量评价和Meta 分析。结果 共1772 篇英文文献，经剔除重复和不符合纳入标准者，最终纳入11 篇文献（包括回顾性病例分析10 篇和病例观察研究1 篇）共160 例利妥昔单抗治疗的难治性重症肌无力患者［包括血清抗乙酰胆碱受体（AChR）抗体阳性88例、抗肌肉特异性受体酪氨酸激酶（MuSK）抗体阳性65 例、抗AChR 和MuSK 抗体阴性7 例］。Meta 分析显示，利妥昔单抗治疗血清抗AChR 抗体阳性的难治性重症肌无力的临床症状改善率为77%（95%CI：0.642 ~ 0.899，P = 0.030），治疗血清抗MuSK 抗体阳性或抗AChR和MuSK 抗体阴性的难治性重症肌无力的临床症状改善率为73%（95%CI：0.631 ~ 0.829，P = 0.048），且可以显著减少激素日剂量［治疗前31.80（20.00，45.90）mg/d、治疗后6.81（3.44，8.00）mg/d，减量21.70（15.50，42.46）mg/d；Z = 2.366，P = 0.018］；利妥昔单抗不良反应主要包括白细胞减少症、阵发性心房颤动、感染性肺炎、进行性多灶性白质脑病、口腔带状疱疹等。结论 循证医学方法对评价利妥昔单抗治疗难治性重症肌无力的有效性和安全性具有重要意义。利妥昔单抗治疗难治性重症肌无力安全、有效，并可以显著减少激素日剂量。

关键词: 重症肌无力, 受体, 胆碱能, 受体蛋白质酪氨酸激酶类, Meta分析

Abstract:

Objective To evaluate the efficacy and safety of rituximab (RTX) in the treatment of refractory myasthenia gravis (MG). Methods Retrieve relevant retrospective case analysis and observational studies that reported RTX therapy in patients with refractory MG from online databases (January 1, 2000-April 30, 2018) in PubMed, EMBASE/SCOPUS and Cochrane Online Library with key words: rituximab, myasthenia gravis. Quality of studies was evaluated by using Newcastle-Ottawa Scale (NOS). All data were pooled by Stata 12.0 software for Meta-analysis. Results A total of 1772 articles were enrolled, and 10 retrospective case analysis and one observational study with 160 eligible participants taking RTX were finally included after excluding duplicates and those not meeting the inclusion criteria. Among 160 patients, 88 were tested positive for acetylcholine receptor antibody (AChR- Ab+), 65 were tested positive for muscle-specific receptor tyrosine kinase antibody (MuSK-Ab+ ), and 7 were tested negative for two antibodies. Meta-analysis showed the overall effective rate of RTX treating refractory MG patients with serum AChR-Ab+ was 77% (95%CI: 0.642-0.899, P = 0.030); the overall effective rate of RTX treating refractory MG patients with serum MuSK-Ab+ was 73% (95%CI: 0.631-0.829, P = 0.048); RTX significantly reduced average daily dose of corticosteroids [before treatment 31.81 (20.00, 45.90) mg/d, after treatment 6.81 (3.44, 8.00) mg/d, decrement 21.70 (15.50, 42.46) mg/d; Z = 2.366, P = 0.018]; the main side effects of RTX were leukopenia, paroxysmal atrial fibrillation, infectious pneumonia, progressive multifocal leukoencephalopathy (PML), oral herpes zoster, et al. Conclusions Critical findings have been demonstrated in the evidence?based evaluation on efficacy and safety of RTX in the treatment of refractory MG. The effect of RTX on refractory MG is remarkable, and can significantly reduce the average daily dosage of corticosteroids.

Key words: Myasthenia gravis, Receptors, cholinergic, Receptor protein-tyrosine kinases, Meta-analysis