A contemporary analysis of the Australian clinical and genetic landscape of spinal muscular atrophy: a registry based study

Abstract

Background: New paradigms of diagnosis and treatment have changed the neurodegenerative trajectory for individuals with spinal muscular atrophy (SMA). Registries are a critical tool to provide real-world data on treatment patterns, their effects and health care provision within this evolving paradigm of care. This study aimed to evaluate the phenotypic and genotypic landscape, treatment patterns and health impact of SMA in Australia through the national registry.; Methods: This cross-sectional study investigated demographic, clinical and genetic information, sequelae of weakness, treatment patterns and patient-reported outcomes amongst individuals with SMA enrolled in the Australian Neuromuscular Disease Registry (ANMDR) from 1st January 2020 to 30th April 2023. Descriptive statistics were used for analysis and Chi-Squared or Fisher's exact tests for associations.; Findings: 195 individuals with SMA enrolled into the ANMDR. 5/195 (2.6%) were deceased by censor date. Of (n = 190) individuals living with SMA, 104/190 (54.7%) were children. Minimum Australian prevalence was 0.73/100,000. SMN2 copies were inversely associated with phenotype in those with homozygous SMN1 deletions ( p < 0.0001 )). Treatment was utilised in 154/190 (81%) of the population, with 65/137 (47.6%) of individuals perceiving improvements with therapeutic intervention on Patient/Parent Global Impression of Improvement scale ( p < 0.0001 ). Engagement with multidisciplinary care practitioners was significantly higher among children with SMA than adults (93% versus 12%, p < 0.0001 ).; Interpretation: Despite diagnostic and therapeutic advances, mortality and the multi-systemic health impact of SMA continue to be experienced within the Australian population. Healthcare provision must align with patient-centred outcomes, adapting to meeting their changing but ongoing care requirements. The study identified the considerable unmet need for multidisciplinary care, not only for adults with SMA but also for the emerging cohort of treated children, emphasising the imperative for comprehensive healthcare provision to address their evolving needs.; Funding: No funding was received for this study.; Competing Interests: RF has received speaker honoraria from Biogen and travel support from Novartis, PTC Therapeutics and Pfizer. AJK is the site principal or sub-investigator for Novartis Clinical Trials, and has received honoraria for advisory board participation from Sanofi and Novartis. LS has received speaker fees for lectures and development of educational material from Biogen, Pfizer, AbbVie and travel support from Abbott. CL has received honoraria from Biogen for speaker engagements and from Biogen and Roche for advisory board participation. KJJ has received honoraria for lectures, presentations, and speaker bureau engagements from Novartis Global gene Therapy Network Steering Committee. COG has received speaker fees from Biogen. IW has received honoraria for work performed including educational activities and attendance at advisory board meetings from Biogen, Novartis, Roche. EMY is the principal investigator of the Australian Neuromuscular Diseases Registry (ANMDR) at the Murdoch Children's Research Institute. EMY is a site principal or sub-investigator for Biogen and Novartis clinical trials in spinal muscular atrophy, and the institution has received funds for contract research related to the conduct of these trials. EMY has received honoraria for advisory board participation from Biogen and Roche, including honoraria paid to their institution from Biogen for advisory board participation. MAF is the recipient of NHMRC investigator grant (APP1194940). MAF is a site principal investigator for Biogen, Roche and Novartis Gene Therapies, Inc., clinical trials, and their institution has received funds for contract research related to the conduct of these trials. MAF has received honoraria for educational events from Biogen, Novartis Gene Therapies, and Roche. MAF has received honoraria for contributions to scientific advisory boards for Biogen, Roche and Novartis Gene Therapies, Inc., MAF is a medical director of Muscular Dystrophy New South Wales (not for profit, unpaid). DK has received the NHMRC Investigator grant 2024 (2026317), and has received honoraria from Biogen, Roche and Novartis for presentations, for participation on Advisory Board from Biogen, and travel support from Biogen. The ANMDR is supported by research grants from TREAT-NMD, MD-NSW, The Daniel Ferguson Foundation, Save our Sons Duchenne Foundation, the Western Australian government, Biogen, Roche, PTC therapeutics, and Pfizer. (© 2024 The Authors.)