Motor Function and Safety of Nusinersen and Risdiplam in Asian Patients with Types 2–4 Spinal Muscular Atrophy (SMA): A Systematic Review and Meta-Analysis

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-02-17 DOI:10.1007/s12325-024-03101-7

Xinran Zhao, Yihan Liao, Jingyu Zhao, Lin Zhu, Jun Liu, Min Zhang, Wei Li

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Abstract

Introduction

The aim of this study was to systematically appraise and synthesize real-world data of motor function and safety in Asian patients with spinal muscular atrophy (SMA) treated with nusinersen or risdiplam.

Methods

This study systematically searched PubMed, Cochrane, Embase, CNKI, and Wanfang databases for real-world studies (RWS) published from January 2017 to January 2024. Based on the prespecified study selection and eligibility criteria, RWS evaluating motor function and/or safety outcomes in patients with types 2–4 SMA treated with nusinersen or risdiplam were included, while studies without Asian populations were excluded. The Newcastle–Ottawa Scale (NOS) was used to assess the risk of bias, and a meta-analysis was conducted for each motor function endpoint based on the extracted data.

Results

A total of 26 RWS were included in this review, of which 17 reporting main motor function outcomes were included in the meta-analyses. Intervention in all 17 studies was nusinersen; none included risdiplam. Statistically significant improvement was observed in Revised Upper Limb Module (RULM) [Mean difference (MD) = 2.27 (0.84, 3.71)], Hammersmith Functional Motor Scale Expanded (HFMSE) [MD = 2.62 (1.79, 3.45)] and six-minute walk test (6MWT) [MD = 18.29 (9.12, 27.45)] when treated with nusinersen ≤ 6 months and > 6 months (HFMSE [MD = 4.34 (3.54, 5.14)]; 6MWT [MD = 45.59 (12.92, 78.27)]). Clinically meaningful responses of motor milestones were also observed when treating nusinersen over 6 months: 54.4% (0.305, 0.772) for RULM, 53.0% (0.273, 0.779) for HFMSE and 97.1% (0.819, 1.000) for 6MWT. A total of 19 studies addressed safety outcomes. Reported adverse events were consistent with the expected safety profile for nusinersen.

Conclusion

Our study suggests that nusinersen is associated with a statistically significant and clinically meaningful motor function improvement in Asian patients with types 2–4 SMA in the real-world setting. No unexpected safety concern was observed for nusinersen. Motor function and safety outcomes after risdiplam could not be evaluated in this patient population under real-world settings due to limited studies.

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Nusinersen和Risdiplam治疗亚洲2-4型脊髓性肌萎缩症（SMA）患者的运动功能和安全性：一项系统综述和荟萃分析。

本研究的目的是系统地评价和综合亚洲脊髓性肌萎缩症（SMA）患者接受nusinersen或risdiplam治疗后的运动功能和安全性的真实数据。方法：本研究系统检索PubMed、Cochrane、Embase、CNKI和万方数据库，检索2017年1月至2024年1月发表的真实世界研究（RWS）。基于预先指定的研究选择和资格标准，纳入了评估nusinersen或risdiplam治疗的2-4型SMA患者运动功能和/或安全性结果的RWS，而排除了没有亚洲人群的研究。采用纽卡斯尔-渥太华量表（NOS）评估偏倚风险，并根据提取的数据对各运动功能终点进行meta分析。结果：本综述共纳入26例RWS，其中17例报告主要运动功能结果被纳入meta分析。所有17项研究的干预均为阴性；没有一个包括瑞斯迪普兰。nusinersen≤6个月和>≤6个月(HFMSE [MD = 4.34(3.54, 5.14)]治疗后，修正上肢模块（RULM）[平均差值(MD) = 2.27(0.84, 3.71)]、Hammersmith功能运动量表扩展（HFMSE） [MD = 2.62(1.79, 3.45)]和6分钟步行测试（6MWT） [MD = 18.29(9.12, 27.45)]均有统计学意义的改善；[md = 45.59(12.92, 78.27)])。在治疗nusinersen超过6个月时，也观察到有临床意义的运动里程碑反应：RULM组为54.4% (0.305,0.772)，HFMSE组为53.0% (0.273,0.779)，6MWT组为97.1%（0.819,1.000）。共有19项研究涉及安全性结果。报告的不良事件与患者预期的安全性相符。结论：我们的研究表明，nusinersen与现实世界中亚洲2-4型SMA患者的运动功能改善有统计学意义和临床意义。没有发现意外的安全隐患。由于研究有限，无法在现实环境下对该患者群体使用瑞斯迪普兰后的运动功能和安全性结果进行评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.