中国循证儿科杂志 ›› 2022, Vol. 17 ›› Issue (4): 302-306.DOI: 10.3969/j.issn.1673-5501.2022.04.007

• 论著 • 上一篇    下一篇

吗替麦考酚酯治疗抗髓鞘少突胶质细胞糖蛋白抗体相关疾病疗效的系统评价和Meta分析

武鹏霞,常旭婷,李尚茹,张捷,吴晔   

  1. 北京大学第一院儿科  北京,100034
  • 收稿日期:2022-05-15 修回日期:2022-08-02 出版日期:2022-08-25 发布日期:2022-09-28
  • 通讯作者: 吴晔

Efficacy of mycophenolate mofetil therapy in myelin oligodendrocyte glycoprotein antibodyassociated disease: A systematic review and meta-analysis

WU Pengxia, CHANG Xuting, LI Shangru, ZHANG Jie, WU Ye   

  1. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
  • Received:2022-05-15 Revised:2022-08-02 Online:2022-08-25 Published:2022-09-28
  • Contact: WU Ye

摘要: 背景:目前预防多相性病程的髓鞘少突胶质细胞糖蛋白抗体相关疾病(MOGAD)的复发常用药物较多,但尚无最佳治疗药物推荐。 目的:探讨吗替麦考酚酯(MMF)治疗MOGAD的疗效。 设计:系统评价和Meta分析。 方法:检索英文数据库:PubMed、Embase、Web of Science和Cochrane,中文数据库:万方、中国知网和维普;检索时限均为从建库至2021年6月1日。纳入研究人群为不限性别、年龄、种族且符合MOGAD诊断标准的文献,以 MMF治疗时间≥6个月为干预,结局指标包括复发率或年复发率(ARR)之一的RCT、非RCT、队列研究、病例系列报告(≥3例)和系统评价/Meta分析;删除MMF治疗符合修正治疗定义,无法获得全文,全文非英文或中文及无法提取本文要求的数据信息的文献;提取数据后采用R软件(V4.2.1)进行Meta分析,并对纳入文献行偏倚风险评价。 主要结局指标:无复发率、ARR。 结果:12篇(161例)文献进入本文分析,其中1篇前瞻性队列研究,11篇病例系列报告。儿童57例,成人80例,成人和儿童不能区分24例。起病年龄1~74岁。随访时间为6~67个月。Meta分析结果显示MMF治疗MOGAD的无复发率为74%(95%CI :58%~89%),各项研究异质性显著(I2=83%,P<0.01);MMF治疗MOGAD后的ARR较治疗前的ARR下降了1.38(95%CI:0.94~1.82)次/年,各项研究无显著异质性(I2=0%,P=0.62)。总体不良反应发生率为8%(7/87),5.7%(5/87)因严重不良反应而中止治疗。 结论:本文研究结果提示,MMF用于MOGAD预防复发的治疗至少6个月,无复发率可达74%,MMF治疗后较治疗前的ARR下降了1.38次/年,尚有待设计更好的干预性研究结果证实。

关键词: 抗髓鞘少突胶质细胞糖蛋白免疫球蛋白G相关疾病(MOGAD), 免疫治疗, 吗替麦考酚酯(MMF), Meta分析

Abstract: Background:There are many widely used immunotherapies for relapse prevention in myelinoligodendrocyte glycoprotein antibodyassociated disease (MOGAD), however, there is no optimal relapse prevention therapy. Objective:To investigate the efficacy of mycophenolate mofetil (MMF) in the treatment of MOGAD. Design:Systematic review and metaanalysis. Methods:English and Chineselanguage articles were searched in PubMed, Embase, Web of Science, Cochrane, Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CQVIP) from the inception to June 1, 2021. All studies related to the efficacy of MMF in treating MOGAD were included regardless of the study design. Inclusion criteria were as the following : the subjects from the original clinical study met the diagnostic criteria of MOGAD, regardless of race, sex, and age; the duration of MMF was ≥ 6 months;the change in annualized relapse rate (ARR) or relapse rate was reported . The literature meeting the following criteria were excluded that studies in which modifying treatment definition was met during treatment; it is unable to obtain the full text; the language is neither English nor Chinese. The metaanalysis was performed using R 4.2.1 and the risk of bias of the included studies was assessed. Main outcome measures:Relapsefree rate and ARR. Results:Twelve studies (161 patients) were included in the metaanalysis, including 1 prospective cohort study and 11 case series reports. Fiftyseven of 161 patients were children, 80 of 161 patients were adults, and age information was unclear in the rest of 24 patients. Age of onset ranged from 1 to 74 years. The followup time ranges from 6 to 67months. Overall, 74% of the patients were relapsefree during followup after MMF therapy (95%CI:58%89%, I2=83%,P<0.01). ARR was significantly decreased after MMF therapy with a mean reduction of 1.38 times/year (95%CI :0.941.82, I2=0%,P=0.62). Adverse effects was reported in 8%(7/87) of patients, and 5.7%(5/87) of patients discontinued MMF therapy due to serious adverse effects. Conclusion:The metaanalysis showed that the relapsefree rate of MOGAD was 74% after MMF treatment for at least 6 months, and the ARR decreased by 1.38 times/year compared with that pretreatment. More highquality studies were still necessary to confirm the result.

Key words: Anti-myelin oligodendrocyte glycoprotein-IgG associated disorders(MOGAD), Immunotherapy, Mycophenolate mofetil(MMF), Meta-analysis