Gavriilaki Maria, Moschou Maria, Pagiantza Maria, Arnaoutoglou Marianthi, Kimiskidis Vasilios
1st Department of Neurology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, Greece.
School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Muscle Nerve. 2025 Mar;71(3):384-391. doi: 10.1002/mus.28327. Epub 2024 Dec 26.
INTRODUCTION/AIMS: Risdiplam was the first orally administered drug approved to treat spinal muscular atrophy (SMA). Efficacy in adults is based on short-term observational studies. This longitudinal study aimed to examine risdiplam's efficacy and safety in adults over a long period of follow-up.
All eligible SMA patients ≥ 16 years old, followed at the Muscular Dystrophy Association Hellas Neuromuscular Diseases Unit between April 2021 and December 2023, were included. We prospectively evaluated motor function, muscle strength, and pulmonary function before and after 6, 12, 18, 24, and 30 months of treatment. Laboratory assessments and patient-reported adverse events were recorded.
Overall, 14 patients (18-57 years, 93% treatment-naive) received risdiplam for a median period of 28.5 months (range 6-30). There were statistically significant improvements in the Hammersmith Functional Motor Scale-Expanded (mean difference [MD] 1.5 [95%CI 0.49-2.42]), Revised Upper Limb Module (MD 1.6 [95%CI 0.54-2.73]), Motor Function Measurement-32 (MD 2.7[95%CI 1.52-3.93]), Medical Research Council scores of the upper (MD 3 [95%CI 0.8-5.2]), and lower (MD 1.7 [95%CI 0.1-3.3]) limbs (all p ≤ 0.05). Eighty-two percent of patients achieved a clinically meaningful improvement (CMI) in at least one scale. Overall, CMI occurred earlier in type 3 patients. SMA functional rating scale and respiratory function tests remained stable over time. Fifty-seven percent of patients did not report any adverse events. None discontinued treatment.
Risdiplam treatment over 30 months resulted in overall CMI in most treated adult SMA type 2 or 3 patients. Outpatient drug administration and overall patient management proved feasible and safe. Larger studies are warranted.
引言/目的：利司扑兰是首个获批用于治疗脊髓性肌萎缩症（SMA）的口服药物。其在成人中的疗效基于短期观察性研究。这项纵向研究旨在长期随访中检验利司扑兰在成人中的疗效和安全性。
纳入2021年4月至2023年12月在希腊肌肉萎缩症协会神经肌肉疾病科接受随访的所有符合条件的16岁及以上SMA患者。我们前瞻性评估了治疗6、12、18、24和30个月前后的运动功能、肌肉力量和肺功能。记录实验室评估结果和患者报告的不良事件。
总体而言，14名患者（年龄18 - 57岁，93%为初治患者）接受利司扑兰治疗的中位时间为28.5个月（范围6 - 30个月）。在哈默史密斯功能运动量表扩展版（平均差值[MD] 1.5 [95%置信区间0.49 - 2.42]）、修订上肢模块（MD 1.6 [95%置信区间0.54 - 2.73]）、运动功能测量-32（MD 2.7[95%置信区间1.52 - 3.93]）、医学研究委员会上肢（MD 3 [95%置信区间0.8 - 5.2]）和下肢（MD 1.7 [95%置信区间0.1 - 3.3]）评分方面均有统计学显著改善（所有p≤0.05）。82%的患者在至少一个量表上实现了具有临床意义的改善（CMI）。总体而言，3型患者的CMI出现得更早。SMA功能评定量表和呼吸功能测试随时间保持稳定。57%的患者未报告任何不良事件。无人停止治疗。
30个月以上的利司扑兰治疗使大多数接受治疗的2型或3型成年SMA患者实现了总体CMI。门诊给药和总体患者管理证明是可行且安全的。有必要开展更大规模的研究。
