Peer-reviewed article

Long-Term Comparative Efficacy and Safety of Risdiplam versus Nusinersen in Children with Type 1 Spinal Muscular Atrophy (SMA)

Neil Hawkins, Gautam Sajeev, Rachel Evans, Anadi Mahajan, David Alexander Scott et al. · 1 Nov 2023

Summary

Written by AI, not yet AICS's view · claude-haiku-4-5-20251001

This study compared two disease-modifying drugs for Type 1 spinal muscular atrophy (SMA) in children: risdiplam and nusinersen. Using statistical methods to adjust for differences between patient groups, researchers found that children treated with risdiplam had better survival rates, fewer serious complications, and greater improvements in motor function compared to those treated with nusinersen. The analysis followed children for up to 4.5 years. The findings suggest risdiplam may be more effective, though the study was not a direct head-to-head comparison.

Key points

Risdiplam reduced death rate by 78% compared with nusinersen in children with Type 1 SMA
Risdiplam reduced death or permanent ventilation by 81% compared with nusinersen
Risdiplam reduced serious adverse events by 57% compared with nusinersen
Children on risdiplam were 45% more likely to achieve motor milestones (HINE-2) and 189% more likely to achieve CHOP-INTEND responses
Median follow-up was 3 years with effective sample size of 40.6 for risdiplam group after statistical matching

Limitations

This was an indirect comparison using statistical adjustment rather than a randomized controlled trial, so unmeasured differences between the two treatment groups could have influenced results. The analysis adjusted only for known prognostic factors (age, disease duration, baseline motor score), and other unmeasured factors may still confound the findings.

Abstract

Background/Purpose: Risdiplam (EVRYSDI) and nusinersen (SPINRAZA) are approved disease-modifying therapies (DMTs) for SMA. There are no long-term data on relative efficacy and safety of these DMTs. In the absence of head-to-head trials, indirect treatment comparisons adjusted for cross-trial differences can inform treatment decision-making. This study compared long-term efficacy and safety of risdiplam versus nusinersen in children with Type 1 SMA. Methods: Patient-level risdiplam data from 58 children in FIREFISH (Parts 1 and 2; NCT02913482) and published nusinersen data from 81 children in SHINE (ENDEAR cohort; NCT02193074) were compared. Matching-adjusted indirect comparisons (MAICs) were conducted, adjusting for age at first dose, disease duration and baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score. Cox proportional-hazards models were used to compare survival and times to Hammersmith Infant Neurological Examination, Module 2 (HINE-2) and CHOP-INTEND responses, and time to first serious adverse event (SAE). Results: After matching, relevant baseline characteristics were identical across groups. Effective sample size for risdiplam was 40.6. Median follow-up was 3 years (range: 2.5–4.5). Compared with nusinersen, risdiplam led to reductions of 78% in the rate of death, 81% in the rate of death or permanent ventilation and 57% in the rate of SAEs, and increases of 45 and 189% in the rate of achieving HINE-2 and CHOP-INTEND responses, respectively. While adjustments were made for known prognostic factors, as with any non-randomized comparison, results may be confounded by unobserved baseline differences between groups. Conclusion: MAIC suggested that children with Type 1 SMA treated with risdiplam may experience greater improvements in survival, motor function, and time to first SAE compared with nusinersen. These analyses leveraged the longest follow-up available from FIREFISH and SHINE. Additional data sources should be consulted to expand on these findings. Publication History Article published online: 13 November 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Findings the Hub has extracted

Each claim below is labelled by its type of design and links back to this report.

SurvivalDevelopment

Problem

Type 1 spinal muscular atrophy in children, characterized by severe progressive muscle weakness, respiratory failure, and early mortality

Intervention: Treatment with risdiplam (EVRYSDI) versus nusinersen (SPINRAZA), both disease-modifying therapies for SMA
Population: 58 children treated with risdiplam in FIREFISH trial and 81 children treated with nusinersen in SHINE/ENDEAR cohort, all with Type 1 SMA

Key finding

Risdiplam reduced mortality rate by 78% compared with nusinersen (Cox model comparison)

Experimental