Hagenacker Tim, Maggi Lorenzo, Coratti Giorgia, Youn Bora, Raynaud Stephanie, Paradis Angela D, Mercuri Eugenio
Department of Neurology Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Essen, Germany.
Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Neurol Ther. 2024 Oct;13(5):1483-1504. doi: 10.1007/s40120-024-00653-2. Epub 2024 Sep 2.
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.
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.
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.
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.
关于5q相关脊髓性肌萎缩症（SMA）青少年和成人患者，诺西那生的临床试验数据有限。我们进行了一项系统文献综述（SLR）和荟萃分析，以评估诺西那生在临床实践中对SMA青少年和成人患者的有效性。
我们的检索纳入了2016年12月23日至2022年7月1日发表的论文，这些论文纳入了≥5名年龄≥13岁的个体，并包含≥1项选定运动功能结局（哈默史密斯功能运动量表扩展版（HFMSE）、修订上肢模块（RULM）和六分钟步行试验（6MWT））的≥6个月数据。对于荟萃分析，使用随机效应模型汇总效应量。为了解疾病严重程度对治疗效果的影响，按SMA类型和步行状态进行亚组荟萃分析。
14篇出版物纳入了539例患者，随访时间长达24个月，符合SLR的纳入标准。患者年龄为13 - 72岁，大多数（99%）为II型或III型SMA。在组水平上始终观察到运动功能有适度改善或稳定。HFMSE从基线有显著平均增加[2.3分（95%CI 1.3 - 3.3）]，32.1%（21.7 - 44.6）的患者在18个月时表现出具有临床意义的增加（≥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个月时表现出具有临床意义的改善（≥2分）。在能行走的患者中，6MWT平均距离显著增加25.0米（8.9 - 41.2），50.9%（33.4 - 68.2）的患者在14个月时表现出具有临床意义的改善（≥30米）。受影响较轻的患者HFMSE增加更大，而受影响较重的患者RULM改善更大。
研究结果提供了确凿证据，表明诺西那生对许多患有广泛类型SMA的青少年和成人患者在改善或稳定运动功能方面是有效的。
