Effectiveness of Nusinersen in Adolescents and Adults with Spinal Muscular Atrophy: Systematic Review and Meta-analysis.

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-09-02 DOI:10.1007/s40120-024-00653-2

Tim Hagenacker, Lorenzo Maggi, Giorgia Coratti, Bora Youn, Stephanie Raynaud, Angela D Paradis, Eugenio Mercuri

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引用次数: 0

Abstract

Introduction: Nusinersen clinical trials have limited data on adolescents and adults with 5q-associated spinal muscular atrophy (SMA). We conducted a systematic literature review (SLR) and meta-analysis to assess effectiveness of nusinersen in adolescents and adults with SMA in clinical practice.

Methods: Our search included papers published 12/23/2016 through 07/01/2022 with ≥ 5 individuals ≥ 13 years of age and with ≥ 6 months' data on ≥ 1 selected motor function outcomes [Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), and Six-Minute Walk Test (6MWT)]. For meta-analysis, effect sizes were pooled using random-effects models. To understand treatment effects by disease severity, subgroup meta-analysis by SMA type and ambulatory status was conducted.

Results: Fourteen publications including 539 patients followed up to 24 months met inclusion criteria for the SLR. Patients were age 13-72 years and most (99%) had SMA Type II or III. Modest improvement or stability in motor function was consistently observed at the group level. Significant mean increases from baseline were observed in HFMSE [2.3 points (95% CI 1.3-3.3)] with 32.1% (21.7-44.6) of patients demonstrating a clinically meaningful increase (≥ 3 points) at 18 months. Significant increases in RULM were consistently found, with a mean increase of 1.1 points (0.7-1.4) and 38.3% (30.3-47.1) showing a clinically meaningful improvement (≥ 2 points) at 14 months. Among ambulatory patients, there was a significant increase in mean 6MWT distance of 25.0 m (8.9-41.2) with 50.9% (33.4-68.2) demonstrating a clinically meaningful improvement (≥ 30 m) at 14 months. The increases in HFMSE were greater for less severely affected patients, whereas more severely affected patients showed greater improvement in RULM.

Conclusions: Findings provide consolidated evidence that nusinersen is effective in improving or stabilizing motor function in many adolescents and adults with a broad spectrum of SMA.

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Nusinersen 对青少年和成人脊髓性肌肉萎缩症患者的疗效：系统回顾与元分析》。

简介：有关5q相关脊髓性肌萎缩症（SMA）青少年和成人患者的纽西奈森临床试验数据有限。我们进行了一项系统性文献综述（SLR）和荟萃分析，以评估纽西奈森在青少年和成人SMA患者临床实践中的有效性：我们的检索纳入了2016年12月23日至2022年1月7日发表的论文，其中≥5名患者年龄≥13岁，且≥6个月的数据中≥1项选定的运动功能结果[哈默史密斯功能运动量表-扩展版（HFMSE）、修订版上肢模块（RULM）和六分钟步行测试（6MWT）]。在进行荟萃分析时，使用随机效应模型对效应大小进行了汇总。为了解不同疾病严重程度的治疗效果，还按SMA类型和非卧床状态进行了分组荟萃分析：14篇文献（包括随访24个月的539名患者）符合SLR的纳入标准。患者年龄在 13-72 岁之间，大多数（99%）为 SMA II 型或 III 型。在组别水平上，运动功能持续得到适度改善或保持稳定。与基线相比，HFMSE 的平均值显著增加[2.3 分（95% CI 1.3-3.3）]，32.1%（21.7-44.6）的患者在 18 个月时表现出有临床意义的增加（≥ 3 分）。RULM持续显著增加，平均增加1.1分（0.7-1.4），38.3%（30.3-47.1）的患者在14个月时显示出有临床意义的改善（≥2分）。在非卧床患者中，6MWT 平均距离显著增加了 25.0 米（8.9-41.2），50.9%（33.4-68.2）的患者在 14 个月时表现出有临床意义的改善（≥ 30 米）。病情较轻的患者HFMSE的增加幅度更大，而病情较重的患者RULM的改善幅度更大：研究结果提供了确凿证据，证明纽西奈森能有效改善或稳定多种 SMA 青少年和成人患者的运动功能。

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

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication 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 neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. 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