From the Institute I-motion (K.A.-G., A.M.S., E.G., M.A., T.G., L.S.), Pediatric Intensive Care Unit (J. Rambaud), and Department of Pediatric Pneumology (J.T.), Armand Trousseau Hospital, Paris, France; Neuromuscular Reference Centre (A.D., L.S.), Citadelle Hospital, Liege, Belgium; Department of Pediatric Physical Medicine and Rehabilitation (C.V.), University Hospital of Lyon; Department of Child Neurology (C.C.), University Hospital of Toulouse; Department of Child Neurology (J. Ropars), University Hospital of Brest; Department of Pediatrics (M.C.), University Hospital of Dijon, France; Department of Neurology & Neurosurgery (I.C.), Brain Center Rudolf Magnus, UMC Utrecht, the Netherlands; Royal Manchester Children's Hospital (I.H.), Manchester; Department of Paediatric Neurology (M.I.) University Hospital Southampton; John Walton Muscular Dystrophy Research Centre (C.M.-B.), Institute of Genetic Medicine, Newcastle University; and Dubowitz Neuromuscular Centre (M.S.), UCL Great Ormond Street Institute of Child Health, London, UK.
Neurology. 2018 Oct 2;91(14):e1312-e1318. doi: 10.1212/WNL.0000000000006281. Epub 2018 Aug 29.
To evaluate the safety and clinical efficacy of nusinersen in patients older than 7 months with spinal muscular atrophy type 1 (SMA1).
Patients with SMA1 were treated with nusinersen by intrathecal injections as a part of the Expanded Access Program (EAP; NCT02865109). We evaluated patients before treatment initiation (M0) and at 2 months (M2) and 6 months (M6) after treatment initiation. Survival, respiratory, and nutritional data were collected. Motor function was assessed with the modified Hammersmith Infant Neurologic Examination Part 2 (HINE-2) and physiotherapist scales adjusted to patient age (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders and the Motor Function Measure 20 or 32).
We treated 33 children ranging in age from 8.3 to 113.1 months between December 2016 and May 2017. All patients were alive and were continuing treatment at M6. Median progress on the modified HINE-2 score was 1.5 points after 6 months of treatment ( < 0.001). The need for respiratory support significantly increased over time. There were no statistically significant differences between patients presenting with 2 and those presenting with 3 copies of the survival motor neuron 2 () gene.
Our results are in line with the phase 3 study for nusinersen in patients with SMA1 treated before 7 months of age and indicate that patients benefit from nusinersen even at a later stage of the disease.
NCT02865109.
This study provides Class IV evidence that for patients with SMA1 who are older than 7 months, nusinersen is beneficial.
评估诺西那生钠在 7 个月以上脊髓性肌萎缩症 1 型（SMA1）患者中的安全性和临床疗效。
SMA1 患者通过鞘内注射接受诺西那生钠治疗，这是扩展准入计划（EAP；NCT02865109）的一部分。我们在治疗开始前（M0）以及治疗开始后 2 个月（M2）和 6 个月（M6）评估患者。收集生存、呼吸和营养数据。运动功能采用改良的哈默史密斯婴儿神经病学检查第 2 部分（HINE-2）和根据患者年龄调整的物理治疗师量表（费城儿童医院婴儿神经肌肉疾病测试和运动功能测量 20 或 32）进行评估。
我们在 2016 年 12 月至 2017 年 5 月期间治疗了 33 名年龄在 8.3 至 113.1 个月的儿童。所有患者均存活，且在 M6 时继续接受治疗。治疗 6 个月后，改良 HINE-2 评分中位数提高了 1.5 分（<0.001）。随着时间的推移，对呼吸支持的需求显著增加。携带 2 份和 3 份生存运动神经元 2 （SMN2）基因的患者之间没有统计学上的显著差异。
我们的结果与在 7 个月龄之前接受治疗的 SMA1 患者的诺西那生钠 3 期研究一致，表明即使在疾病的晚期，患者也能从诺西那生钠中获益。
临床试验.gov 标识符：NCT02865109。
本研究提供了 IV 级证据，表明对于 7 个月以上的 SMA1 患者，诺西那生钠是有益的。
