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

Area of Science:

• Neurology
• Genetics
• Pharmacology

Background:

• Spinal Muscular Atrophy (SMA) is a rare genetic neuromuscular disorder causing progressive muscle weakness and mobility loss.
• SMA impacts patients and caregivers significantly, requiring extensive medical and supportive care.
• SMA is categorized into Types 1-4, with potential for presymptomatic identification.

Purpose of the Study:

• To systematically review the safety and effectiveness of nusinersen and risdiplam in treating Spinal Muscular Atrophy (SMA).

Main Methods:

• A comprehensive search of research databases, websites, and existing systematic reviews was performed.
• Data screening, extraction, and quality assessment were conducted by two independent authors, with a third resolving discrepancies.
• A total of 131 studies across 148 sources were included in this review, registered with PROSPERO (CRD42024512226).

Main Results:

• Both nusinersen and risdiplam demonstrated improvements in motor function and achievement of developmental milestones, alongside high survival rates in most SMA types.
• While motor function gains were consistent, outcomes related to bulbar and respiratory function, and ventilation requirements, exhibited variability.
• Adverse events were frequently observed across all treatments and SMA types, with serious cases, including fatalities in Types 1 and 2, being reported.

Conclusions:

• Nusinersen and risdiplam exhibit clinical effectiveness and safety for all SMA types, but outcome variability and limited comparative data create uncertainty.
• The current evidence base highlights the need for more rigorous, high-quality randomized controlled trials to further solidify treatment efficacy and safety profiles for SMA.