Effectiveness and Safety of Nusinersen and Risdiplam in Spinal Muscular Atrophy: A Systematic Review

Abstract

Objective: Spinal Muscular Atrophy (SMA) is a rare genetic disorder marked by progressive muscle weakness and mobility loss. It has a profound physical, emotional and social impact on patients and caregivers, requiring comprehensive medical and supportive care. SMA is classified into Types 1–4, with some individuals identified presymptomatically. This systematic review examined the safety and effectiveness of nusinersen and risdiplam for treating SMA. Methods: We searched research databases, relevant websites and existing systematic reviews. Screening, data extraction and quality assessment were conducted independently by two authors, with discrepancies resolved by a third. Internal quality appraisal ensured methodological rigour. A total of 131 studies reported in 148 sources were included. The review is registered with PROSPERO (CRD42024512226). Results: Both treatments showed improvements in motor function and milestones, with high survival rates across most SMA types. Motor function improvements were consistent, but other outcomes—such as bulbar and respiratory function, and ventilation needs—were variable. Adverse events were common across all treatments and SMA types, with some serious cases reported, including deaths in Types 1 and 2. Interpretation: This comprehensive review highlights the clinical effectiveness and safety of nusinersen and risdiplam across all SMA types. However, variability in outcomes and limited comparative data introduce uncertainty. The findings underscore the need for more high-quality randomised controlled trials to strengthen the evidence base for SMA treatment.