Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study
Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study
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DOI：
10.1016/s1474-4422(20)30037-5
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发表时间：
2020-04-01
期刊：
影响因子：
48
通讯作者：
Kleinschnitz, Christoph
中科院分区：
文献类型：
--
作者：
Hagenacker, Tim;Wurster, Claudia D.;Kleinschnitz, Christoph
背景
诺西那生钠被批准用于治疗所有年龄患者的所有类型和阶段的5q脊髓性肌萎缩症。尽管临床试验已表明该药物治疗的婴幼儿运动功能有所改善，但成人的数据却很缺乏。我们旨在评估诺西那生钠在5q脊髓性肌萎缩症成人患者中的安全性和有效性。
方法
我们在德国的10个学术临床站点进行了一项观察性队列研究。基因确诊为5q脊髓性肌萎缩症（年龄16 - 65岁）且外显子7、8纯合缺失或两者皆缺失，或具有复合杂合突变的患者符合纳入标准，并按照说明书接受诺西那生钠治疗，最短治疗时间为6个月，随访最长达14个月。主要结局是在第6、10和14个月时评估的扩展版哈默史密斯功能性运动量表（HFMSE）总分的变化，并基于前后比较。本研究在德国临床试验注册中心注册（注册号DRKS00015702）。
结果
在2017年7月13日至2019年5月1日期间，对173名患者进行了筛选，其中139名（80%）符合数据分析条件。其中，124名（89%）被纳入6个月分析，92名（66%）被纳入10个月分析，57名（41%）被纳入14个月分析；缺失基线HFMSE评分的患者被排除在这些分析之外。与基线相比，6个月时平均HFMSE评分显著提高（平均差值1.73 [95%置信区间1.05 - 2.41]，p
Background Nusinersen is approved for the treatment of 5q spinal muscular atrophy of all types and stages in patients of all ages. Although clinical trials have shown improvements in motor function in infants and children treated with the drug, data for adults are scarce. We aimed to assess the safety and efficacy of nusinersen in adults with 5q spinal muscular atrophy.Methods We did an observational cohort study at ten academic clinical sites in Germany. Patients with genetically confirmed 5q spinal muscular atrophy (age 16-65 years) with a homozygous deletion of exons 7, 8, or both, or with compound heterozygous mutations were eligible for inclusion and received nusinersen treatment in accordance with the label for a minimum treatment time of 6 months to a follow-up of up to 14 months. The primary outcome was the change in the total Hammersmith Functional Motor Scale Expanded (HFMSE) score, assessed at months 6, 10, and 14, and based on pre-post comparisons. This study is registered with the German Clinical Trials Register (number DRKS00015702).Findings Between July 13, 2017, and May 1, 2019, 173 patients were screened, of whom 139 (80%) were eligible for data analysis. Of these, 124 (89%) were induded in the 6-month analysis, 92 (66%) in the 10-month analysis, and 57 (41%) in the 14-month analysis; patients with missing baseline HFMSE scores were excluded from these analyses. Mean HFMSE scores were significantly increased compared with baseline at 6 months (mean difference 1.73 [95% CI 1.05-2.411, p