REGISTRE SMA FRANCE: A nationwide observational registry of patients with spinal muscular atrophy in France.

Abstract

BackgroundSpinal muscular atrophy (SMA) is a severe neurodegenerative disease affecting children. Three innovative disease-modifying therapies (DMTs)-nusinersen, risdiplam, and onasemnogene abeparvovec-are available for treatment.ObjectiveTo provide a descriptive overview of patients enrolled in the Registre SMA France until July 22, 2024.MethodsRegistre SMA France is a multicenter, national observational registry that includes patients with SMA-children and adults, treated or untreated. Data collection began retrospectively in 2016 and prospectively in 2020, with a 10-year follow-up plan. The coordinating center is the neuropediatric department of Garches Hospital (AP-HP), while methodological and, regulatory and operational management, are provided by the Clinical Research Unit of AP-HP Paris-Saclay. Financial support is provided through unrestricted grants from Biogen, Novartis, and Roche. Data on patient characteristics, medical and surgical follow-up, treatments, adverse events, and quality of life are recorded via structured forms, with additional modules developed as required (e.g., hematological monitoring post-gene therapy in 2021). Data quality is ensured through routine checks and periodic monitoring.ResultsBy July 22, 2024, 1299 patients from 59 centers were enrolled (299 SMA1, 502 SMA2, 469 SMA3, 19 SMA4, 10 presymptomatic). Of these, 76.2% received DMT (nusinersen: 46.1%, risdiplam: 23.2%, onasemnogene abeparvovec: 9.2%), with 21.5% undergoing sequential or combination therapy. Major complications included ventilatory support (SMA1: 69.9%, SMA2: 64.5%, SMA3: 18.1%), enteral feeding (SMA1: 56.2%SMA1), and spine surgery (SMA2: 24.5%). Survival was significantly higher in treated SMA1 and SMA2 cases.ConclusionThis registry serves as a key resource for understanding the clinical course and treatment outcomes of SMA in the real world, supporting future research and informing clinical and policy decisions in the era of DMTs.Trial registrationNCT04177134.