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Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Spinal muscular atrophy (SMA), a rare neurodegenerative disorder with an estimated incidence of 1 in 6,000 to 10,000 live births, is the leading genetic cause of mortality in infants and children. Since the approval of new disease modifying treatments (DMTs; Spinraza in 2017, Zolgensma in 2020, and Evrysdi in 2021), studies have reported modified disease trajectories compared to the known SMA natural history. To describe the natural history of SMA and its progression during the use of DMTs in real-world settings, a retrospective cohort study was designed. Feasibility assessment identified six appropriate SMA registries to take part, comprising data from nine European countries (3 clinician-based registries: Belgium, Czech Republic & Slovakia, Sweden and 3 patient-based registries: Germany & Austria, Spain, UK & Ireland) between April 2008 and May 2023 federated in the TREAT-NMD network. Among 2,188 SMA patients with genetically confirmed 5q SMA, more patients had SMA type 2 (41.8%) than type 3 (35.6%) and type 1 (19.7%); 1,321 (60.3% overall) were treated with Spinraza (75,9%), Evrysdi (30.5%) or Zolgensma (7.6%), and 847 (38.7%) never received treatment. Functional status and motor milestones were rarely reported in never treated patients. Among treated patients, best functional status for SMA types 1, 2, and 3 was "sitter" for 36.6%, 60.9%, and 5.3%, and "walker" for 12.0%, 24.6%, and 87.8% respectively. Best motor milestone for types 1 and 2 was "sit without support" for 27.2% and 38.0%, and "roll onto side" for 18.5% and 2.0% respectively. For type 3, 63.4% reported "climb stairs" and 19.3% reported "walk 10 meters without assistance". Functional status and motor milestones were well captured after treatment but rarely reported before, limiting evaluation of treatment related changes. Areas of improvement for registry data quality have been identified to reduce data missingness, increase standardization, and enhance their utility to inform regulatory decision making. Disclaimer: "This study was funded by the European Medicines Agency and registered in EU PAS (EUPAS50476). The views expressed in this abstract are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agency/agencies or organizations with which the authors are employed/affiliated." [ABSTRACT FROM AUTHOR]

Risdiplam (EVRYSDI®) is a disease-modifying therapy approved for the treatment of spinal muscular atrophy (SMA). The efficacy of risdiplam has been demonstrated in clinical trials that included adult patients, but the real-world effectiveness of risdiplam in adults has not yet been extensively investigated. Natural history studies have shown a slow, progressive decline in motor function in adult patients with SMA. It remains unclear how treatment with risdiplam may influence this trajectory in a real-world clinical setting. As such, this study aims to describe adult patients with SMA treated with risdiplam in terms of their demographic and clinical characteristics, treatment patterns and motor function outcomes, and explore, if possible, the comparison of these outcomes with untreated patients. This non-interventional, retrospective cohort study will use data from six registries (clinician and patient reported) from within the TREAT-NMD network (Australia, Belgium, Canada, Czech Republic & Slovakia, Germany & Austria, and the UK & Ireland) to identify adult patients with SMA treated with risdiplam and where feasible, compare with an untreated patient population. Appropriate adjustment methods will be explored to account for potential confounders where possible, and appropriate statistical models will be used to perform comparisons with untreated patients. As of the submission of this abstract, the analysis is ongoing. Available data will be presented with descriptive statistics. In sum, this study will add to the growing real-world evidence for risdiplam in adults. This study will help to contextualise the effect of risdiplam in this patient population and that of untreated patients. [ABSTRACT FROM AUTHOR]