利妥昔单抗治疗难治性重症肌无力有效性和安全性的Meta分析  

Efficacy and safety of rituximab in the treatment of refractory myasthenia gravis:Meta-analysis

作　　者：储珊珊 陈邓[1] 朱丽娜[1] 谭戈[1] 徐达[1] 王海姣[1] 张宇[1] 刘凌[1] CHU Shan-shan;CHEN Deng;ZHU Li-na;TAN Ge;XU Da;WANG Hai-jiao;ZHANG Yu;LIU Ling(Department of Neurology,West China Hospital,Sichuan University,Chengdu 610041,Sichuan,China)

机构地区：[1]四川大学华西医院神经内科,成都610041

出　　处：《中国现代神经疾病杂志》2018年第7期494-500,共7页Chinese Journal of Contemporary Neurology and Neurosurgery

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(Pub Med)、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(ACh R)抗体阳性88例、抗肌肉特异性受体酪氨酸激酶(Mu SK)抗体阳性65例、抗ACh R和Mu SK抗体阴性7例]。Meta分析显示,利妥昔单抗治疗血清抗ACh R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Mu SK抗体阳性或抗ACh R和Mu SK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。Objective To evaluate the efficacy and safety of rituximab（RTX） in the treatment ofrefractory myasthenia gravis（MG）. Methods Retrieve relevant retrospective case analysis andobservational studies that reported RTX therapy in patients with refractory MG from online databases（January 1, 2000-April 30, 2018） in Pub Med, EMBASE/SCOPUS and Cochrane Online Library with keywords： 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 articleswere enrolled, and 10 retrospective case analysis and one observational study with 160 eligible participantstaking 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（ACh R-Ab ＋）, 65 weretested positive for muscle-specific receptor tyrosine kinase antibody（Mu SK-Ab ＋）, and 7 were testednegative for two antibodies. Meta-analysis showed the overall effective rate of RTX treating refractory MGpatients with serum ACh R-Ab ＋ was 77%（95%CI： 0.642-0.899, P = 0.030）; the overall effective rate ofRTX treating refractory MG patients with serum Mu SK-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 mainside effects of RTX were leukopenia, paroxysmal atrial fibrillation, infectious pneumonia, progressivemultifocal leukoencephalopathy（PML）, oral herpes zoster, et al. Conclusions Critical findings have beendemonstrated in the evidence-based evaluation on efficacy and safety of RTX in the treatment of refractoryMG. The effect of RTX on refractory MG is remarkable, and can significantly reduce the average dailydosage of corticosteroids.

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 

分 类 号：R746.1[医药卫生—神经病学与精神病学]