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》。

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

摘要

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。

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

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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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

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