INTRODUCTION Treatment of children with spinal muscular atrophy (SMA) now includes disease modifying drugs such as nusinersen. Real-world data can provide new insight on the efficacy and safety of nusinersen for treatment of children with SMA. AIM The aim of our study is to evaluate the effect of treatment of children and young adults with SMA type I, II and III at various stages of the disease after 14 months of treatment with nusinersen. METHODS In this prospective, two-center (in Slovenia and Czech Republic) study, data from all patients with a genetically confirmed diagnosis of SMA before 19 years of age who were treated with nusinersen were collected before initiation of treatment, and after 6 and 14 months of treatment. Various standardized motor scales and a questionnaire that focused on daily-life activities were used. RESULTS Form both centers, 61 patients from 2 months to 19 years of age were enrolled in the study. Sixteen had SMA type I (median age 5.2 years); 32 had SMA type II (median age 8.9 years); and 13 had SMA type III (median age 8.6 years). Patients had 2-4 copies of the SMN2 gene. One patient died in the study period and one discontinued treatment. After 14 months of treatment, SMA type I (p = 0.002) and type II (p = 0.002) patients had significantly better outcomes, while type III patients showed a trend towards improvement (p = 0.051) on motor scales. Younger age at the initiation of treatment and a higher number of SMN2 copies is related to a better outcome. Younger children also seem to improve faster compared to older children. No serious side effects were reported. CONCLUSION The results of our study which included patients of various SMA types and stages of the disease suggest that treatment with nusinersen benefits patients, regardless of SMA type. Earlier age at the initiation of treatment and a higher number of SMN2 copies were related to a better outcome, however even some patients of higher age and/or later stage of the disease benefited from the treatment. Our study also suggests that nusinersen is safe to use, as no major side effects, requiring discontinuation of treatment, were reported. There is an unmet need for novel standardized tests and biomarkers, which could help guide clinician's decisions on the selection of best treatment options and monitor treatment success.

中文翻译：

---

nusinersen 治疗脊髓性肌萎缩症的儿童和年轻人

介绍 脊髓性肌萎缩症 (SMA) 儿童的治疗现在包括改善疾病的药物，例如 nusinersen。真实世界的数据可以为 nusinersen 治疗儿童 SMA 的有效性和安全性提供新的见解。目的 我们研究的目的是评估在接受 nusinersen 治疗 14 个月后，对处于疾病不同阶段的 I、II 和 III 型 SMA 儿童和年轻人的治疗效果。方法 在这项前瞻性、两中心（在斯洛文尼亚和捷克共和国）的研究中，收集了所有在 19 岁之前接受 nusinersen 治疗的遗传学确诊 SMA 患者的数据，这些患者在治疗开始前以及治疗后 6 和 14几个月的治疗。使用了各种标准化的运动量表和关注日常生活活动的问卷。结果 来自两个中心的 61 名年龄在 2 个月至 19 岁之间的患者参加了这项研究。16 人患有 SMA I 型（中位年龄 5.2 岁）；32 人患有 SMA II 型（中位年龄 8.9 岁）；13 人患有 SMA III 型（中位年龄 8.6 岁）。患者有 2-4 个 SMN2 基因拷贝。一名患者在研究期间死亡，一名患者停止治疗。治疗 14 个月后，SMA I 型（p = 0.002）和 II 型（p = 0.002）患者的预后明显更好，而 III 型患者在运动量表上显示出改善的趋势（p = 0.051）。开始治疗时年龄越小，SMN2 拷贝数越多，结果越好。与年龄较大的孩子相比，年龄较小的孩子似乎也进步得更快。没有报告严重的副作用。结论我们的研究结果包括各种 SMA 类型和疾病阶段的患者，表明使用 nusinersen 治疗有益于患者，无论 SMA 类型如何。治疗开始时的较早年龄和较高的 SMN2 拷贝数与更好的结果有关，但即使是一些年龄较大和/或疾病晚期的患者也从治疗中受益。我们的研究还表明，nusinersen 可以安全使用，因为没有报告需要停止治疗的重大副作用。对新型标准化测试和生物标志物的需求尚未得到满足，这有助于指导临床医生选择最佳治疗方案并监测治疗成功率。治疗开始时的较早年龄和较高的 SMN2 拷贝数与更好的结果有关，但即使是一些年龄较大和/或疾病晚期的患者也从治疗中受益。我们的研究还表明，nusinersen 可以安全使用，因为没有报告需要停止治疗的重大副作用。对新型标准化测试和生物标志物的需求尚未得到满足，这有助于指导临床医生选择最佳治疗方案并监测治疗成功率。治疗开始时的较早年龄和较高的 SMN2 拷贝数与更好的结果有关，但即使是一些年龄较大和/或疾病晚期的患者也从治疗中受益。我们的研究还表明，nusinersen 可以安全使用，因为没有报告需要停止治疗的重大副作用。对新型标准化测试和生物标志物的需求尚未得到满足，这有助于指导临床医生选择最佳治疗方案并监测治疗成功率。需要停止治疗的报告。对新型标准化测试和生物标志物的需求尚未得到满足，这有助于指导临床医生选择最佳治疗方案并监测治疗成功率。需要停止治疗的报告。对新型标准化测试和生物标志物的需求尚未得到满足，这有助于指导临床医生选择最佳治疗方案并监测治疗成功率。