INTRODUCTION Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a homozygous deletion of the survival motor neuron (SMN) 1 gene. Nusinersen is an antisense oligonucleotide enhancing the production of the SMN protein. It has received approval by the European Medicines Agency (EMA) in 2017, based on the clinical trials demonstrating the effectiveness of nusinersen in several types of SMA. In Hungary, the first patient received nusinersen treatment in April 2018. Our aim is to summarize our experience regarding the efficacy, safety and tolerability of nusinersen in our patients. METHODS Data were collected retrospectively in all types of SMA patients (type 1-3) starting treatment with nusinersen in Hungary between April 2018 and December 2019. Motor functions were evaluated at baseline, at the fourth and all following injections. RESULTS By 31st December 2019, nusinersen therapy was initiated in 54 patients at either of the two Hungarian treatment centres. Mean age of the patients at the start of the treatment was 6.3 years (±5,4 range 0.4-17.9). 13 patients are type 1 (mean 0.78 ± 0.27, range 0.4-1.5 yrs), 21 patients are type 2 (mean 4.5 ± 3.3, range 1.3-12 yrs), 23 patients are type 3 (mean 10.9 ± 5.2, range 2.9-17.9 yrs). Fourteen patients had severe scoliosis, four of them underwent spine stabilizing surgery. During the study period 340 injections were administered without any new safety concerns emerging. The data of 38 patients, who had completed the first six treatments, were included in the final statistical analysis. Motor function has improved in most of the children. By the 307th day visit, on average, a 14.9 (±5,1) point improvement was measured on the CHOP INTEND scale in type 1 patients (p = 0.016). All patients with type 1 SMA who performed the motor evaluation (7/10) have improved by more than four (7-21) points. Regarding type 2 patients, a 7.2 (range -2- 17) point increase from baseline (p < 0.001) on the Hammersmith Functional Motor Scale Expanded (HFMSE) and 4.3 (range: 2-9) point increase (p = 0.031) on the Revised Upper Limb Module (RULM) were found. The distance of the 6 min walk test also increased by 33.9 m on average (range -16 - 106), in type 3 patients. CONCLUSION According to our results nusinersen has the same safety and tolerability profile as in the clinical trials. In a heterogenic patient population of SMA type 1 and 2, nusinersen showed similar efficacy as seen in the pivotal studies. A clinically and statistically significant improvement of motor functions was also detectable in type 3 patients with heterogeneous age distribution.

中文翻译：

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nusinersen 对 1、2 和 3 型脊髓性肌萎缩症的疗效：来自匈牙利患者的真实世界数据

简介 脊髓性肌萎缩症 (SMA) 是一种常染色体隐性遗传病，由运动神经元存活 (SMN) 1 基因纯合缺失引起。Nusinersen 是一种反义寡核苷酸，可增强 SMN 蛋白的产生。基于临床试验证明 nusinersen 在几种类型的 SMA 中的有效性，它于 2017 年获得了欧洲药品管理局 (EMA) 的批准。在匈牙利，第一位患者于 2018 年 4 月接受了 nusinersen 治疗。我们的目的是总结我们在患者中使用 nusinersen 的有效性、安全性和耐受性方面的经验。方法 回顾性收集 2018 年 4 月至 2019 年 12 月在匈牙利开始接受 nusinersen 治疗的所有类型 SMA 患者（1-3 型）的数据。在基线时评估运动功能，在第四次和所有后续注射。结果 到 2019 年 12 月 31 日，在两个匈牙利治疗中心中的任何一个，对 54 名患者开始了 nusinersen 治疗。治疗开始时患者的平均年龄为 6.3 岁（±5.4 范围 0.4-17.9）。13 例患者为 1 型（平均 0.78 ± 0.27，范围 0.4-1.5 岁），21 例患者为 2 型（平均 4.5 ± 3.3，范围 1.3-12 岁），23 例患者为 3 型（平均 10.9 ± 5.2，范围 2.9- 17.9 岁）。14 名患者患有严重的脊柱侧弯，其中 4 名接受了脊柱稳定手术。在研究期间进行了 340 次注射，没有出现任何新的安全问题。完成前6次治疗的38例患者的数据纳入最终统计分析。大多数儿童的运动功能得到改善。到第 307 天访问时，平均为 14.9 (±5, 1) 在 1 型患者的 CHOP INTEND 量表上测量分数改善 (p = 0.016)。所有进行运动评估 (7/10) 的 1 型 SMA 患者的改善超过四 (7-21) 分。对于 2 型患者，Hammersmith 功能性运动量表扩展 (HFMSE) 比基线增加 7.2（范围 -2-17）点（p < 0.001），并且增加 4.3（范围：2-9）点（p = 0.031）（p = 0.031）发现了修订的上肢模块 (RULM)。在 3 型患者中，6 分钟步行测试的距离也平均增加了 33.9 m（范围 -16 - 106）。结论 根据我们的结果，nusinersen 具有与临床试验相同的安全性和耐受性特征。在 SMA 1 型和 2 型异源患者群体中，nusinersen 显示出与关键研究中所见相似的功效。