诺西那生钠对改善儿童脊髓性肌萎缩症患者呼吸支持和营养支持及安全性的Meta分析

A Meta-analysis of Nusinersen in improving respiratory and nutritional support and safety in children with spinal muscular atrophy

关键词:  脊髓性肌萎缩症  诺西那生钠  有效性  安全性  儿童  Meta分析

Key words:  spinal muscular atrophy  nusinersen  efficacy  safety  children  Meta-analysis

摘要:

摘要： 目的 采用Meta分析方法评估诺西那生钠改善儿童脊髓性肌萎缩症（SMA）患者的呼吸支持、营养支持及其治疗的安全性，为临床治疗SMA提供循证依据。方法 通过检索Cochrane Library、Embase、PubMed、Web of science、ClinicalTrial.gov、CBM、CNKI、万方和维普数据库，检索时限为建库至2022年12月31日，提取资料并评价文献质量，采用软件 RevMan 5.4进行Meta分析。结果 共纳入11篇队列研究，1153例年龄＜18岁SMA患者，Meta分析结果显示，诺西那生钠治疗期间，儿童SMA患者运动功能指标有较大改善，WHO运动里程碑改善率为0.26[95%CI(0.20，0.32)，P＜0.00001]，但对SMA患儿的呼吸支持、营养支持需求没有积极的影响；总的不良反应发生率（发生人数/总人数）为0.31 [95%CI (0.19，0.41)，P＜0.00001]，死亡率为0.03[95%CI (0.01，0.06)，P＝0.04]，停药率0.04[95%CI (0.03，0.06)，P＝0.03]，其中在发生的不良反应中严重不良反应占比（发生例次/总例次）为0.65[95%CI (0.44，0.86)，P＜0.00001]。主要不良反应的表现为呼吸道感染、腰椎穿刺综合征、腹部症状、发热、急性呼吸衰竭、其他感染、其他不良反应如骨折、癫痫发作、脑脊液漏、虚弱等。结论 在运动功能改善的同时，我们没有观察到诺西那生钠对儿童SMA 1、2、3型患者的呼吸机支持、营养支持需求有积极影响，在儿童中的不良反应较高。但目前研究的样本量较小，均为观察性研究，证据级别低，上述结论尚待更多高质量研究予以验证。

Abstract:

ABSTRACT: OBJECTIVE Meta-analysis was used to evaluate respiratory support, nutritional support and safety in children with spinal muscular atrophy (SMA) treated with nusinersen, to provide evidence-based evidence for clinical treatment of SMA. METHODS Cochrane Library, Embase, PubMed, Web of science, ClinicalTrial.gov, CBM, CNKI, Wanfang and VIP databases were searched from inception to december 31, 2022. After extracting data and evaluating literature quality, RevMan 5.4 software was used for Meta-analysis. RESULTS A total of 11 cohort studies were included, and involving 1153 SMA patients (＜18 years), during nusinersen treatment, motor function indicators showed significant improvements in Children with SMA, WHO motor milestone improvement rate is 0.26[95%CI(0.20, 0.32)，P＜0.00001], but respiratory support and nutritional support were not positively affected, and the overall incidence of adverse events (occurrence numbers/total number of persons)was 0.31[95%CI (0.19, 0.41), P < 0.00001], death rate was 0.03 [95%CI (0.01, 0.06), P＝0.04], treatment withdrawal rate was 0.04[95%CI (0.03, 0.06), P＝0.03]; among the adverse reactions, the proportion of severe adverse reactions (occurrence cases/total cases) was 0.65[95%CI (0.44, 0.86), P＜0.00001]. The main adverse events were respiratory tract infection, lumbar puncture syndrome, abdominal symptoms, fever, acute respiratory failure, other infections, other adverse events such as fractures, seizures, cerebrospinal fluid leakage, weakness. CONCLUSION While improvements in motor function, we could not observe a positive efect of nusinersen treatment on the need for ventilator support or nutritional support in children with SMA type 1, 2 and 3, and has higher adverse reactions in children. However, the sample size of the current studies is small, all observational studies, and the evidence is low-quality, More high-quality studies were still necessary to confirm the result.