Abstract：
BACKGROUND: Spinal muscular atrophy (SMA) is a rare neuromuscular disorder leading to early death in the majority of affected individuals without treatment. Recently, targeted treatment approaches including Onasemnogene Abeparvovec (OA) were introduced. This study describes the first real-world experience with OA in Switzerland.
METHODS: Prospective observational case series study using data collected within the Swiss Registry for Neuromuscular Disorders from SMA patients treated with OA. Development of motor, bulbar and respiratory function, appearance of scoliosis, and safety data (platelet count, liver function, and cardiotoxicity) were analyzed.
RESULTS: Nine individuals were treated with OA and followed for 383 ± 126 days: six SMA type 1 (of which two with nusinersen pretreatment), one SMA type 2, and two pre-symptomatic individuals. In SMA type 1, CHOP Intend score increased by 28.1 from a mean score of 20.5 ± 7.6 at baseline. At end of follow-up, 50% of SMA type 1 patients required nutritional support and 17% night-time ventilation; 67% developed scoliosis. The SMA type 2 patient and two pre-symptomatically treated individuals reached maximum CHOP Intend scores. No patient required adaptation of the concomitant prednisolone treatment, although transient decrease of platelet count and increase of transaminases were observed in all patients. Troponin-T was elevated prior to OA treatment in 100% and showed fluctuations in 57% thereafter.
CONCLUSIONS: OA is a potent treatment for SMA leading to significant motor function improvements. However, the need for respiratory and especially nutritional support as well as the development of scoliosis must be thoroughly evaluated in SMA type 1 patients even in the short term after OA treatment.
METHODS: Prospective observational case series study using data collected within the Swiss Registry for Neuromuscular Disorders from SMA patients treated with OA. Development of motor, bulbar and respiratory function, appearance of scoliosis, and safety data (platelet count, liver function, and cardiotoxicity) were analyzed.
RESULTS: Nine individuals were treated with OA and followed for 383 ± 126 days: six SMA type 1 (of which two with nusinersen pretreatment), one SMA type 2, and two pre-symptomatic individuals. In SMA type 1, CHOP Intend score increased by 28.1 from a mean score of 20.5 ± 7.6 at baseline. At end of follow-up, 50% of SMA type 1 patients required nutritional support and 17% night-time ventilation; 67% developed scoliosis. The SMA type 2 patient and two pre-symptomatically treated individuals reached maximum CHOP Intend scores. No patient required adaptation of the concomitant prednisolone treatment, although transient decrease of platelet count and increase of transaminases were observed in all patients. Troponin-T was elevated prior to OA treatment in 100% and showed fluctuations in 57% thereafter.
CONCLUSIONS: OA is a potent treatment for SMA leading to significant motor function improvements. However, the need for respiratory and especially nutritional support as well as the development of scoliosis must be thoroughly evaluated in SMA type 1 patients even in the short term after OA treatment.
摘要：
背景：脊髓性肌萎缩症（SMA）是一种罕见的神经肌肉疾病，导致大多数未经治疗的受影响个体早期死亡。最近,介绍了包括OnasemnogeneAbeparvovec（OA）在内的靶向治疗方法。这项研究描述了在瑞士使用OA的第一个实际经验。
方法：前瞻性观察性病例系列研究，使用瑞士神经肌肉疾病注册中心收集的数据，来自接受OA治疗的SMA患者。电机的发展，球和呼吸功能，脊柱侧弯的外观，和安全性数据(血小板计数，肝功能,和心脏毒性）进行分析。
结果：9例接受OA治疗，随访383±126天：6例1型SMA（其中2例接受nusinersen预处理），1例2型SMA和2例症状前个体。在1型SMA中，CHOPIntend评分从基线时的平均评分20.5±7.6增加28.1。在后续行动结束时，50％的SMA1型患者需要营养支持和17％的夜间通气；67％发生脊柱侧弯。SMA2型患者和两个对症治疗前的个体达到最大CHOP意图得分。没有患者需要适应伴随的泼尼松龙治疗，尽管在所有患者中均观察到血小板计数一过性下降和转氨酶升高。肌钙蛋白-T在OA治疗前以100%升高,并且此后表现出57%的波动。
结论：OA是SMA的有效治疗方法，可显著改善运动功能。然而,对于SMA1型患者,即使在OA治疗后短期内,也必须全面评估其对呼吸,尤其是营养支持的需求以及脊柱侧弯的发展.
方法：前瞻性观察性病例系列研究，使用瑞士神经肌肉疾病注册中心收集的数据，来自接受OA治疗的SMA患者。
结果：9例接受OA治疗，随访383±126天：6例1型SMA（其中2例接受nusinersen预处理），
结论：OA是SMA的有效治疗方法，可显著改善运动功能。
