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低剂量利妥昔单抗治疗重症肌无力的疗效与安全性:一项系统评价和荟萃分析

Efficacy and safety of low-dose rituximab in the treatment of myasthenia gravis: a systemic review and meta-analysis.

作者信息

Yang Xishuai, Zhang Wei, Guo Junhong, Ma Chunlin, Li Bingxia

机构信息

Department of Neurology, Changzhi People's Hospital, Changzhi, China.

Department of Neurology, The First School of Shanxi Medical University, Taiyuan, China.

出版信息

Front Neurol. 2024 Sep 25;15:1439899. doi: 10.3389/fneur.2024.1439899. eCollection 2024.

Abstract

BACKGROUND

Rituximab (RTX) is a monoclonal antibody that has been increasingly used in the treatment of myasthenia gravis (MG). In most studies, the therapeutic protocol of RTX has been similar to that adopted for B cell lymphoma, with an increasing number of studies aimed at exploring the efficacy of low-dose RTX in MG. However, the beneficial effects of low-dose RTX in MG remain a subject of critical debate.

METHODS

This study was conducted following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Two reviewers (Xishuai Yang and Bingxia Li) independently conducted searches across multiple databases, including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). A meta-analysis, utilizing representative forest plots, was performed to assess "Improved clinical status" and changes in the Quantitative Myasthenia Gravis (QMG) score before and after treatment.

RESULTS

A total of 17 studies involving 292 patients were included in the meta-analysis. A noticeable improvement in clinical status was observed in 91% of patients at the final follow-up after therapy (95% CI: 84-96%, < 0.001). The QMG score showed a significant reduction following the treatment, with a standardized mean difference (SMD) of -1.69 (95% CI: -2.21 to -1.16, = 6.29, < 0.001). In the acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) group, 90% of patients achieved improved clinical status (95% CI: 80-97%, < 0.001) and the QMG score significantly decreased after low-dose RTX treatment, with an SMD of -1.51 (95% CI: -0.80 to -2.21, = 4.50, < 0.001). In the muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) group, 97% of patients achieved improved clinical status (95% CI: 89-100%, < 0.001). The QMG score also significantly decreased following low-dose RTX treatment, with an SMD of -2.31 (95% CI: -2.99 to -1.62, = 6.60, < 0.001). Adverse effects were reported in 29 out of 207 patients (14%, including infusion reactions in 22 patients (10.1%), infections in three patients (1.45%), cytopenia in two patients (0.96%), eosinophilia in one patient (0.48%), and hemiplegia in one patient (0.48%). Additionally, one patient (0.48%) succumbed to complications from invasive thymoma.

CONCLUSION

Our meta-analysis shows that low-dose RTX is both effective and safe for treating MG.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO, identifier: CRD42024509951.

摘要

背景

利妥昔单抗(RTX)是一种单克隆抗体,越来越多地用于治疗重症肌无力(MG)。在大多数研究中,RTX的治疗方案与用于B细胞淋巴瘤的方案相似,越来越多的研究旨在探索低剂量RTX在MG中的疗效。然而,低剂量RTX在MG中的有益作用仍是一个备受争议的话题。

方法

本研究按照PRISMA(系统评价和Meta分析的首选报告项目)指南进行。两名评审员(杨希帅和李冰夏)独立在多个数据库中进行检索,包括PubMed、MEDLINE、EMBASE、Web of Science、Cochrane图书馆和中国知网(CNKI)。利用代表性森林图进行Meta分析,以评估“临床状态改善”以及治疗前后重症肌无力定量评分(QMG)的变化。

结果

Meta分析共纳入17项研究,涉及292例患者。治疗后最后一次随访时,91%的患者临床状态有显著改善(95%CI:84 - 96%,P < 0.001)。治疗后QMG评分显著降低,标准化平均差(SMD)为 -1.69(95%CI: -2.21至 -1.16,Z = 6.29,P < 0.001)。在乙酰胆碱受体抗体阳性重症肌无力(AChR - MG)组中,90%的患者临床状态改善(95%CI:80 - 97%,P < 0.001),低剂量RTX治疗后QMG评分显著降低,SMD为 -1.51(95%CI: -0.80至 -2.21,Z = 4.50,P < 0.001)。在肌肉特异性激酶抗体阳性重症肌无力(MuSK - MG)组中,97%的患者临床状态改善(95%CI:89 - 100%,P < 0.001)。低剂量RTX治疗后QMG评分也显著降低,SMD为 -2.31(95%CI: -2.99至 -1.62,Z = 6.60,P < 0.001)。207例患者中有29例(14%)报告了不良反应,包括22例(10.1%)输液反应、3例(1.45%)感染、2例(0.96%)血细胞减少、1例(0.48%)嗜酸性粒细胞增多和1例(0.48%)偏瘫。此外,1例患者(0.48%)死于侵袭性胸腺瘤并发症。

结论

我们的Meta分析表明,低剂量RTX治疗MG有效且安全。

系统评价注册

PROSPERO,标识符:CRD42024509951。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36a9/11461331/4acfa1d21778/fneur-15-1439899-g0001.jpg

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