Abstract：
OBJECTIVE: This systematic review provides an update on outcomes for patients with spinal muscular atrophy (SMA) type 1 to 4 treated with approved therapeutics, including the most recent, risdiplam, for an observation period of up to 48 months.
METHODS: A systematic literature search was conducted in July 2023 in four databases. Selected publications were assessed for internal validity and risk of bias by two authors and relevant data were extracted into standardised tables. Results were summarised narratively as substantial heterogeneity of studies prevents meaningful quantitative analysis.
RESULTS: Twenty observational studies and one RCT were included in the analysis, fifteen studies on nusinersen, one on onasemnogene abeparvovec and two on risdiplam. Evidence supports the effectiveness of the therapies in motor function improvement for up to 48 months of follow-up in the SMA types specified in their respective indications. Better results were observed with earlier treatment initiation and higher baseline function. Whilst motor improvement was consistently observed, regardless of SMA type or treatment used, we noted no significant improvements in respiratory and nutritional outcomes. Quality of life endpoints were rarely investigated. Adverse events were common but seldom classified as treatment-related except for post-lumbar puncture syndrome, which was frequently reported across nusinersen studies.
CONCLUSIONS: The treatment of SMA with the new therapies changes the disease phenotype with changes in motor function far exceeding any improvement in respiratory and nutritional function. Questions persist on long-term efficacy, potential regressions, impact on quality of life and social functioning, therapy duration, and discontinuation indicators.
METHODS: A systematic literature search was conducted in July 2023 in four databases. Selected publications were assessed for internal validity and risk of bias by two authors and relevant data were extracted into standardised tables. Results were summarised narratively as substantial heterogeneity of studies prevents meaningful quantitative analysis.
RESULTS: Twenty observational studies and one RCT were included in the analysis, fifteen studies on nusinersen, one on onasemnogene abeparvovec and two on risdiplam. Evidence supports the effectiveness of the therapies in motor function improvement for up to 48 months of follow-up in the SMA types specified in their respective indications. Better results were observed with earlier treatment initiation and higher baseline function. Whilst motor improvement was consistently observed, regardless of SMA type or treatment used, we noted no significant improvements in respiratory and nutritional outcomes. Quality of life endpoints were rarely investigated. Adverse events were common but seldom classified as treatment-related except for post-lumbar puncture syndrome, which was frequently reported across nusinersen studies.
CONCLUSIONS: The treatment of SMA with the new therapies changes the disease phenotype with changes in motor function far exceeding any improvement in respiratory and nutritional function. Questions persist on long-term efficacy, potential regressions, impact on quality of life and social functioning, therapy duration, and discontinuation indicators.
摘要：
目的：本系统综述提供了使用已批准的治疗方法治疗的1至4型脊髓性肌萎缩症（SMA）患者的最新结果，包括最近的,risdiplam,长达48个月的观察期。
方法：于2023年7月在四个数据库中进行了系统的文献检索。由两位作者评估了选定出版物的内部有效性和偏倚风险，并将相关数据提取到标准化表格中。结果被叙述性地总结为研究的实质性异质性阻止了有意义的定量分析。
结果：分析包括20项观察性研究和1项RCT，15项关于Nusinersen的研究,一个在onasemnogeneabeparvovec上，两个在risdiplam上。证据支持在各自适应症中指定的SMA类型的长达48个月的随访中，治疗在运动功能改善中的有效性。较早的治疗开始和较高的基线功能观察到更好的结果。虽然一直观察到运动改善，无论使用的SMA类型或治疗方法，我们注意到呼吸和营养结局无显著改善.很少研究生活质量终点。不良事件很常见，但很少被归类为治疗相关，除了腰椎穿刺后综合征。这在nusinersen研究中经常报道。
结论：用新疗法治疗SMA改变疾病表型，运动功能的改变远远超过呼吸和营养功能的任何改善。长期疗效问题仍然存在，潜在的回归，对生活质量和社会功能的影响，治疗持续时间,和停止指标。
方法：于2023年7月在四个数据库中进行了系统的文献检索。由两位作者评估了选定出版物的内部有效性和偏倚风险，并将相关数据提取到标准化表格中。结果被叙述性地总结为研究的实质性异质性阻止了有意义的定量分析。
结果：分析包括20项观察性研究和1项RCT，15项关于Nusinersen的研究,一个在onasemnogeneabeparvovec上，两个在risdiplam上。证据支持在各自适应症中指定的SMA类型的长达48个月的随访中，治疗在运动功能改善中的有效性。较早的治疗开始和较高的基线功能观察到更好的结果。虽然一直观察到运动改善，无论使用的SMA类型或治疗方法，我们注意到呼吸和营养结局无显著改善.很少研究生活质量终点。不良事件很常见，但很少被归类为治疗相关，除了腰椎穿刺后综合征。这在nusinersen研究中经常报道。
结论：用新疗法治疗SMA改变疾病表型，运动功能的改变远远超过呼吸和营养功能的任何改善。长期疗效问题仍然存在，潜在的回归，对生活质量和社会功能的影响，治疗持续时间,和停止指标。
