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Original research
Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1–3
  1. Archana Chacko1,2,
  2. Peter D Sly1,
  3. Robert S Ware3,
  4. Nelufa Begum1,
  5. Sean Deegan2,
  6. Nicole Thomas4,
  7. Leanne M Gauld2
  1. 1Centre for Children's Research, The University of Queensland, South Brisbane, Queensland, Australia
  2. 2Respiratory and Sleep Medicine, Children's Health Queensland Hospital and Health Service, South Brisbane, Queensland, Australia
  3. 3Menzies Health Institute, Griffith University, Brisbane, Queensland, Australia
  4. 4Neuromuscular Physiotherapy Department, Queensland Children's Hospital, South Brisbane, Queensland, Australia
  1. Correspondence to Dr Archana Chacko, The University of Queensland Child Health Research Centre, Brisbane, QLD 4072, Australia; archana.bodapati{at}hotmail.com

Abstract

Introduction Nusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown.

Aim To assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment.

Methods A prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test.

Results Twenty-eight patients (15 male, aged 0.08–18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was −0.58 (95% CI −0.75 to −0.41), and post initiation was −0.25 (95% CI −0.46 to −0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea–Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1–10.1) at initiation to 2.7 events/hour (IQR 0.7–5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen.

Conclusion The first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.

  • paediatric physician
  • rare lung diseases
  • paediatric lung disaese
  • respiratory muscles
  • respiratory measurement

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Additional individual patient data are available in deidentified format on reasonable request.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Additional individual patient data are available in deidentified format on reasonable request.

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Footnotes

  • Contributors AC and LG planned the study. SD and NT performed lung function and peripheral muscle testing, respectively. AC, NB and RSW analysed the results. AC wrote the manuscript. LG and PDS contributed to writing the manuscript.

  • Funding This study was supported by Biogen Global as an investigator-initiated project.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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