Neuropediatrics 2023; 54(S 01): S1-S32
DOI: 10.1055/s-0043-1777162
Neuromuskuläre Erkrankungen

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

Authors

  • N. Hawkins

    1   Visible Analytics, Oxford, Vereinigtes Königreich
    2   Institute of Health and Wellbeing, University of Glasgow, Glasgow, Vereinigtes Königreich

  • G. Sajeev

    3   Analysis Group, Inc., Boston, Vereinigte Staaten von Amerika

  • R. Evans

    1   Visible Analytics, Oxford, Vereinigtes Königreich

  • A. Mahajan

    4   Bridge Medical Consulting Ltd, London, Vereinigtes Königreich

  • D. A. Scott

    1   Visible Analytics, Oxford, Vereinigtes Königreich

  • J. Nam

    5   F. Hoffmann-La Roche Ltd, Global Access, Basel, Schweiz

  • C. S. Sutherland

    5   F. Hoffmann-La Roche Ltd, Global Access, Basel, Schweiz

  • C. Kokaliaris

    5   F. Hoffmann-La Roche Ltd, Global Access, Basel, Schweiz
Further Information
 
 

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.


No conflict of interest has been declared by the author(s).

Publication History

Article published online:
13 November 2023

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