Switching disease-modifying therapies in patients with spinal muscular atrophy: A systematic review on effectiveness outcomes

Abstract

With multiple disease-modifying therapies now available, treatment switching has become an important clinical consideration in the management of spinal muscular atrophy (SMA). While some switches are prompted by suboptimal clinical response, more commonly they are driven by treatment burden, convenience, or adverse events. This systematic literature review aimed to synthesize existing evidence on therapy switching in SMA, focusing on clinical effectiveness and practical implications to support evidence-informed decision-making in a rapidly evolving therapeutic landscape. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42024600221). A systematic search of PubMed/MEDLINE, Global Health and Embase was conducted between 11 and 14 October 2024. Eligible studies included clinical trials and real-world evidence (RWE) reports describing patients with genetically confirmed SMA who received nusinersen or risdiplam and subsequently switched to nusinersen, risdiplam or onasemnogene abeparvovec. Four studies met the inclusion criteria-three RWE studies and one clinical trial. The variability in measures of central tendency and variability among studies precluded the calculation of pooled summary values. Nonetheless, switching treatments was generally associated with stable motor function, with some improvements reported in selected outcome measures; ventilatory and nutritional support requirements remained largely unchanged. However, long-term outcomes and standardized data were limited. Future research should prioritize robust RWE and post-marketing surveillance to evaluate long-term safety and effectiveness, incorporate standardized switching protocols, and account for SMA genotype-phenotype variation.

Keywords: effectiveness; nusinersen; onasemnogene abeparvovec; real‐world data; risdiplam; spinal muscular atrophy; therapy switch.