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Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study
Nusinersen (Spinraza®) improves survival of infants with hereditary proximal spinal muscular atrophy and motor function in children up to 12 years. Population-based assessments of treatment efficacy are limited and confined to select cohorts of patients. We performed a nationwide, population-based,...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9651026/ https://www.ncbi.nlm.nih.gov/pubmed/36382221 http://dx.doi.org/10.1093/braincomms/fcac269 |
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author | Scheijmans, Féline E V Cuppen, Inge van Eijk, Ruben P A Wijngaarde, Camiel A Schoenmakers, Marja A G C van der Woude, Danny R Bartels, Bart Veldhoen, Esther S Oude Lansink, Irene L B Groen, Ewout J N Asselman, Fay-Lynn Wadman, Renske I van der Pol, W Ludo |
author_facet | Scheijmans, Féline E V Cuppen, Inge van Eijk, Ruben P A Wijngaarde, Camiel A Schoenmakers, Marja A G C van der Woude, Danny R Bartels, Bart Veldhoen, Esther S Oude Lansink, Irene L B Groen, Ewout J N Asselman, Fay-Lynn Wadman, Renske I van der Pol, W Ludo |
author_sort | Scheijmans, Féline E V |
collection | PubMed |
description | Nusinersen (Spinraza®) improves survival of infants with hereditary proximal spinal muscular atrophy and motor function in children up to 12 years. Population-based assessments of treatment efficacy are limited and confined to select cohorts of patients. We performed a nationwide, population-based, single-centre cohort study in children with spinal muscular atrophy younger than 9.5 years at start of treatment in line with reimbursement criteria in the Netherlands. We assessed age-relevant motor function scores, the need for tube feeding, hours of ventilatory support and documented adverse events. We used linear mixed modelling to assess treatment effects. We compared motor function during treatment with natural history data and to individual trajectories of muscle strength and motor function before the start of treatment. We included 71 out of 72 Dutch children who were treated (median age 54 months; range 0–117) and followed them for a median of 38 months (range 5–52). We observed improvement of motor function in 72% and stabilization in another 18% of the symptomatic children, which differed from the natural disease course in a matched cohort of which we had previously collected natural history data. Longitudinal analysis showed that motor function improved up to a median of 24 months (range 12–30) of treatment after which it stabilized. Shorter disease duration at start of treatment resulted in better treatment efficacy (P < 0.01). Sixteen children (23%) achieved new motor milestones. Bulbar and respiratory function did not improve significantly during treatment. In 15 patients from whom treatment-naïve data were available, the pre-treatment trajectory of motor function decline changed to stabilization or improvement after the start of treatment. We documented 82 adverse events after 934 injections (9%) in 45 patients. None of the adverse events led to treatment discontinuation. Intrathecal nusinersen treatment is safe and improves or stabilizes motor function in 90% of young children with spinal muscular atrophy types 1c–3a. We did not observe improvement of respiratory and bulbar functions. |
format | Online Article Text |
id | pubmed-9651026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-96510262022-11-14 Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study Scheijmans, Féline E V Cuppen, Inge van Eijk, Ruben P A Wijngaarde, Camiel A Schoenmakers, Marja A G C van der Woude, Danny R Bartels, Bart Veldhoen, Esther S Oude Lansink, Irene L B Groen, Ewout J N Asselman, Fay-Lynn Wadman, Renske I van der Pol, W Ludo Brain Commun Original Article Nusinersen (Spinraza®) improves survival of infants with hereditary proximal spinal muscular atrophy and motor function in children up to 12 years. Population-based assessments of treatment efficacy are limited and confined to select cohorts of patients. We performed a nationwide, population-based, single-centre cohort study in children with spinal muscular atrophy younger than 9.5 years at start of treatment in line with reimbursement criteria in the Netherlands. We assessed age-relevant motor function scores, the need for tube feeding, hours of ventilatory support and documented adverse events. We used linear mixed modelling to assess treatment effects. We compared motor function during treatment with natural history data and to individual trajectories of muscle strength and motor function before the start of treatment. We included 71 out of 72 Dutch children who were treated (median age 54 months; range 0–117) and followed them for a median of 38 months (range 5–52). We observed improvement of motor function in 72% and stabilization in another 18% of the symptomatic children, which differed from the natural disease course in a matched cohort of which we had previously collected natural history data. Longitudinal analysis showed that motor function improved up to a median of 24 months (range 12–30) of treatment after which it stabilized. Shorter disease duration at start of treatment resulted in better treatment efficacy (P < 0.01). Sixteen children (23%) achieved new motor milestones. Bulbar and respiratory function did not improve significantly during treatment. In 15 patients from whom treatment-naïve data were available, the pre-treatment trajectory of motor function decline changed to stabilization or improvement after the start of treatment. We documented 82 adverse events after 934 injections (9%) in 45 patients. None of the adverse events led to treatment discontinuation. Intrathecal nusinersen treatment is safe and improves or stabilizes motor function in 90% of young children with spinal muscular atrophy types 1c–3a. We did not observe improvement of respiratory and bulbar functions. Oxford University Press 2022-10-31 /pmc/articles/PMC9651026/ /pubmed/36382221 http://dx.doi.org/10.1093/braincomms/fcac269 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Scheijmans, Féline E V Cuppen, Inge van Eijk, Ruben P A Wijngaarde, Camiel A Schoenmakers, Marja A G C van der Woude, Danny R Bartels, Bart Veldhoen, Esther S Oude Lansink, Irene L B Groen, Ewout J N Asselman, Fay-Lynn Wadman, Renske I van der Pol, W Ludo Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study |
title | Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study |
title_full | Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study |
title_fullStr | Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study |
title_full_unstemmed | Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study |
title_short | Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study |
title_sort | population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9651026/ https://www.ncbi.nlm.nih.gov/pubmed/36382221 http://dx.doi.org/10.1093/braincomms/fcac269 |
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