脊髓性肌萎缩症自然病史的系统评价/Meta分析  

Natural history of spinal muscular atrophy:A systematic review and meta-analysis

作　　者：胡超平 李文辉 朱小妹 李奕洁 王慧珊 周水珍 王艺 张崇凡[2] HU Chaoping;LI Wenhui;ZHU Xiaomei;LI Yijie;WANG Huishan;ZHOU Shuizhen;WANG Yi;ZHANG Chongfan(Children's Hospital of Fudan University,Department of Neurology,Shanghai 201102,China;Children's Hospital of Fudan University,GRADE Center,Shanghai 201102,China;Hospital Management Office of Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属儿科医院神经科,上海201102 [2]复旦大学附属儿科医院复旦大学GRADE中心,上海201102 [3]复旦大学医院管理处,上海200032

出　　处：《中国循证儿科杂志》2022年第6期420-425,共6页Chinese Journal of Evidence Based Pediatrics

摘　　要：背景脊髓性肌萎缩症(SMA)主要表现为进行性运动功能倒退,近年来随着基因修复、基因替代治疗药物的应用,设计为RCT的临床试验有悖伦理,因此SMA的自然病史作为治疗对照显得尤为重要。目的系统评价SMA自然病史的生存率和运动功能变化,为SMA的干预作参考。设计系统评价/Meta分析。方法以“脊髓性肌萎缩症”和“自然史”构建中文数据库检索式,以“Spinal Muscular Atrophies(SMA)”和“Natural History”构建英文数据库检索式,分别检索PubMed、Embase、Cochrane、中国知网、中国生物医学文献服务系统和万方数据库,检索时间从建库至2022年9月27日。纳入基因诊断明确为5q SMA,没有给予Nusinersen、Zolgensma和Risdiplam单药或联合治疗的病例,Nusinersen治疗SMA的RCT中的假鞘内给药的病例也被纳入。RCT采用Cochrane RoB 2.0行偏倚风险评价,病例系列报告不进行偏倚风险评价。主要结局指标SMA自然病史状态下总生存率、无事件生存率,基于量表评估的运动功能。结果17篇(1905例)病例系列报告和2篇(83例)Nusinersen治疗SMA的RCT中的假鞘内给药的病例进入本文分析。1型SMA自然病史病例系列报告Meta分析显示,≥6月龄(4篇)、≥12月龄(5篇)和≥18月龄(4篇)总生存率分别为86%(95%CI:74%~98%)、52%(95%CI:38%~66%)和32%(95%CI:22%~43%)。1型SMA自然病史病例系列报告Meta分析显示,≥6月龄(3篇)、≥12月龄(4篇)和≥18月龄(3篇)无事件生存率分别为78%(95%CI:58%~97%)、39%(95%CI:15%~64%)和21%(95%CI:0%~44%)。2篇1型SMA自然病史的病例系列报告数据,随访12月龄时美国费城儿童医院婴儿神经肌病测试(CHOP-INTEND)和Hammersmith婴儿神经病学检查第2部分(HINE-2)应答率均为0,1篇以Nusinersen治疗RCT假操作对照组随访12个月时CHOP-INTEND应答率为2.7%(1/37)。2篇1型SMA自然病史的病例系列报告,WHO运动里程碑12月龄(9例)、18月龄(5例)和24月龄(24例)独坐率均为0。1篇以NBackground Spinal muscular atrophy(SMA)presents with progressive motor function deterioration. Natural history studies of SMA as controls remain crucial considering the advanced treatment strategies of gene repair and gene replacement therapy which make it impossible to perform randomized controlled trials for ethical issues. Objective To systematically analyze the survival rate and trajectory of motor function in the natural history of SMA patients so as to provide benchmark data for the intervention of SMA. Design Systematic review and meta-analysis. Methods PubMed, Embase, Cochrane, CNKI, CBM and Wanfang database were searched by using the keywords of spinal muscular atrophy and natural history, from the inception to November 27th 2022. Treatment-naive patients with genetic diagnosis of 5qSMA as well as sham control cohorts from RCTs of Nusinersen were enrolled. Cochrane RoB 2.0 was used for risk assessment of bias in RCTs, while case series reports were not assessed for risk of bias. Main outcome measures Overall survival rate, event-free survival rate, and motor function based on scale assessment under natural history. Results A total of 17 case series reports(n=1905) and 2 sham controls of Nusinersen in RCTs(n=83) for SMA were included in the analysis. Meta-analysis of case series reports for type 1 SMA under natural history showed that the survival rates at the age of 6 months(4 studies), 12 months(5 studies) and 18 months(4 studies) were 86%(95%CI: 0.74-0.98), 52%(95%CI: 0.38-0.66) and 32%(95%CI: 0.22-0.43), respectively. The meta-analysis of event-free survival rates from natural history case series reports of type 1 SMA showed that it was 78%(95%CI: 58%-97%), 39%(95%CI: 15%-64%) and 21%(95%CI: 0%-44%) at the age of 6 months(3 studies), 12 months(4 studies) and 18 months(3 studies) respectively. In 2 case series reports of type 1 SMA, the response rate of CHOP-INTEND and HINE-2 at 12 months was both 0. In 1 sham control group of RCT with Nusinersen, the response rate of CHOP-INTEND at 12 months was 2.7%(

关 键 词：脊髓性肌萎缩症 自然病史 生存率 运动功能 

分 类 号：R746.4[医药卫生—神经病学与精神病学]