Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • University of Freiburg
  • Kaiser Franz Josef Hospital
  • University of Duisburg-Essen
  • German Society for Muscular Dystrophy (DGM)
  • Ludwig Maximilian University of Munich
  • Innsbruck Medical University
  • Ordensklinikum Linz
  • Technical University of Munich
  • Kepler University Hospital
  • Saarland University
  • Justus Liebig University Giessen
  • University of Tübingen
  • Friedrich Schiller University Jena
  • Hannover Medical School (MHH)
  • University of Hamburg
  • Ruhr University Bochum
  • University Hospital of Würzburg
  • German Red Cross
  • Landeskrankenhaus Bregenz
  • Klinikum Kassel GmbH
  • University of Münster
  • Klinikum Wels - Grieskirchen GmbH
  • Landesklinikum Mödling
  • Friedrich-Alexander University Erlangen-Nürnberg
  • Charité – Universitätsmedizin Berlin
  • Asklepios Clinic Hamburg Nord-Heidberg
  • Heidelberg University 
  • University of Ottawa
  • University of Bonn

Abstract

5q-associated spinal muscular atrophy is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by the European Medicines Agency and Food and Drug Administration for the treatment of spinal muscular atrophy patients, however, long-term experience is still scarce. In contrast to clinical trial data with restricted patient populations and short observation periods, we report here real-world evidence on a broad spectrum of patients with early-onset spinal muscular atrophy treated with nusinersen focusing on effects regarding motor milestones, and respiratory and bulbar insufficiency during the first years of treatment. Within the SMArtCARE registry, all patients under treatment with nusinersen who never had the ability to sit independently before the start of treatment were identified for data analysis. The primary outcome of this analysis was the change in motor function evaluated with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders and motor milestones considering World Health Organization criteria. Further, we evaluated data on the need for ventilator support and tube feeding, and mortality. In total, 143 patients with early-onset spinal muscular atrophy were included in the data analysis with a follow-up period of up to 38 months. We observed major improvements in motor function evaluated with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders. Improvements were greater in children >2 years of age at start of treatment than in older children. 24.5% of children gained the ability to sit independently. Major improvements were observed during the first 14 months of treatment. The need for intermittent ventilator support and tube feeding increased despite treatment with nusinersen. Our findings confirm the increasing real-world evidence that treatment with nusinersen has a dramatic influence on disease progression and survival in patients with early-onset spinal muscular atrophy. Major improvements in motor function are seen in children younger than 2 years at the start of treatment. Bulbar and respiratory function needs to be closely monitored, as these functions do not improve equivalent to motor function.

Details

Original languageEnglish
Pages (from-to)668-677
Number of pages10
JournalBrain
Volume146
Issue number2
Publication statusPublished - 13 Feb 2023
Peer-reviewedYes

External IDs

PubMed 35857854

Keywords

ASJC Scopus subject areas

Keywords

  • SMA, motor function, motor milestones, nusinersen, spinal muscular atrophy, Injections, Spinal, Humans, Infant, Muscular Atrophy, Spinal/drug therapy, Spinal Muscular Atrophies of Childhood/drug therapy, Oligonucleotides/therapeutic use, Child

Library keywords