Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study
Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study
复制标题
DOI：
10.1016/j.nmd.2019.09.007
复制
发表时间：
2019-11-01
影响因子：
2.8
通讯作者：
Farwell, Wildon
中科院分区：
文献类型：
--
作者：
De Vivo, Darryl C.;Bertini, Enrico;Farwell, Wildon
脊髓性肌萎缩症（SMA）是一种神经退行性疾病，与四肢和躯干的严重肌肉萎缩和无力有关。截至2019年3月29日，我们报告了25名遗传诊断为SMA的儿童的中期疗效和安全性结果，这些儿童在婴儿期症状前首次接受nusinersen，这是正在进行的多地点、开放标签、单臂NURTURE试验。15个孩子有2个SMN2副本，10个孩子有3个SMN2副本。最后一次访问时，儿童年龄中位数（范围）为34.8[25.7-45.4]个月，超过了SMA I型或II型症状发作的预期年龄；所有人都活着，没有人需要气管切开术或永久通气。4名（16%）患有2个SMN2拷贝的参与者在急性可逆疾病期间开始使用连续7天的>= 6小时/天的呼吸支持。所有25名参与者都能在没有支持的情况下坐着，23/25（92%）的人能在辅助下行走，22/25（88%）的人能独立行走。研究人员认为，8名婴儿出现了可能与nusinsen有关的不良事件。这些结果（平均随访2.9年）强调了在确定症状前婴儿SMA的遗传诊断和新生儿筛查工作后立即用nusinersen进行积极治疗的重要性。(C) 2019作者。Elsevier B.V.出版
Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety outcomes as of March 29, 2019 in 25 children with genetically diagnosed SMA who first received nusinersen in infancy while presymptomatic in the ongoing Phase 2, multisite, open-label, single-arm NURTURE trial. Fifteen children have two SMN2 copies and 10 have three SMN2 copies. At last visit, children were median (range) 34.8 [25.7-45.4] months of age and past the expected age of symptom onset for SMA Types I or II; all were alive and none required tracheostomy or permanent ventilation. Four (16%) participants with two SMN2 copies utilized respiratory support for >= 6 h/day for >= 7 consecutive days that was initiated during acute, reversible illnesses. All 25 participants achieved the ability to sit without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) achieved walking independently. Eight infants had adverse events considered possibly related to nusinersen by the study investigators. These results, representing a median 2.9 years of follow up, emphasize the importance of proactive treatment with nusinersen immediately after establishing the genetic diagnosis of SMA in presymptomatic infants and emerging newborn screening efforts. (C) 2019 The Authors. Published by Elsevier B.V.