Reference Center for Neuromuscular Disorders, AP-HP Henri Mondor University Hospital, 1 Rue Gustave Eiffel, Créteil, 94010, France.
University Paris Est Créteil, Inserm, U955, IMRB, Créteil, F-94010, France.
Orphanet J Rare Dis. 2024 Nov 20;19(1):430. doi: 10.1186/s13023-024-03442-0.
Risdiplam is a validated treatment for adult SMA patients, but clear guidelines concerning functional assessment at baseline and during the follow-up are still limited, especially in terms of sensible and validated outcome measures able to capture minimal changes in motor performances induced by therapy. The aim of this work is to describe the effect of Risdiplam on a cohort of 6 adult type 2 and type 3 SMA patients, using Motor Function Measure (MFM32) as a standardized scaleto quantify the motor improvements induced by therapy.
Risdiplam at the dose of 5 mg/daily was administered to a population of 6 (4 F;2 M) type 2 (N = 4) and type 3 (N = 2), adult SMA patients. Two patients were previously treated by Nusinersen, later suspended due to side effects. At baseline, all patients received a neuromuscular evaluation and a MFM32 assessment. After the beginning of treatment, we evaluated MFM32, patient reported outcomes (PROs), and adverse events over 7-27 months of follow-up. The MFM32 showed an increased score ranging from + 2.16% to + 7.29% in 4 patients. The improvement was maintained overtime, with two patients presenting the longest follow-up period of 24 and 27 months respectively. Subdomain D3 was ameliorated in 66.6% of patients. Two patients previously treated with Nusinersen maintained the pre-Risdiplam scores. The HFMSE was also performed and failed to show significant improvements after treatment. All patients reported subjective ameliorations. The commonest PROs were improvements in breath fatigue, voice's intelligibility, hand strength and dexterity. Adverse effects were mild and decreased over time.
Risdiplam is a well-tolerated treatment in our cohort of adult type 2 and type 3 SMA patients and resulted in improvement or stabilization in motor functions. MFM32 proved to be sensitive to detect changes induced by therapy. Subjective meaningful improvements were sustained overtime especially in bulbar functions, breath fatigue and distal motor abilities.
利司扑兰是一种已被验证可用于治疗成年 SMA 患者的药物，但在基线和随访期间进行功能评估的明确指南仍然有限，特别是在能够捕捉治疗引起的运动表现微小变化的敏感和经过验证的结果测量方面。本研究的目的是使用运动功能测量（MFM32）作为标准化量表，描述利司扑兰对 6 例成年 2 型和 3 型 SMA 患者的疗效，以量化治疗引起的运动改善。
6 名（4 名女性，2 名男性）2 型（4 例）和 3 型（2 例）成年 SMA 患者接受了每日 5 毫克利司扑兰治疗。其中 2 名患者先前接受过 nusinersen 治疗，因副作用而停药。在基线时，所有患者均接受了神经肌肉评估和 MFM32 评估。治疗开始后，我们在 7-27 个月的随访期间评估了 MFM32、患者报告的结果（PROs）和不良事件。MFM32 在 4 名患者中显示出+2.16%至+7.29%的评分增加。改善在随访期间保持稳定，其中 2 名患者的随访时间最长分别为 24 个月和 27 个月。66.6%的患者的 D3 亚域得到改善。2 名先前接受过 nusinersen 治疗的患者保持了 risdiplam 治疗前的评分。还进行了 HFMSE，但治疗后未显示出显著改善。所有患者均报告主观改善。最常见的 PROs 是呼吸疲劳、语音清晰度、手部力量和灵巧度的改善。不良事件较轻且随时间减少。
利司扑兰在我们的成年 2 型和 3 型 SMA 患者队列中是一种耐受良好的治疗方法，可导致运动功能的改善或稳定。MFM32 证明对检测治疗引起的变化具有敏感性。尤其是在延髓功能、呼吸疲劳和远端运动能力方面，患者的主观改善能够持续保持。
