B R AIN COMMUNICATIONS https://doi.org/10.1093/braincomms/fcac269 BRAIN COMMUNICATIONS 2022: Page 1 of 12 | 1 Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study Féline E. V. Scheijmans, 1 Inge Cuppen, 1 Ruben P. A. van Eijk, 1,2 Camiel A. Wijngaarde, 1 Marja A. G. C. Schoenmakers, 3 Danny R. van der Woude, 3 Bart Bartels, 3 Esther S. Veldhoen, 4 Irene L. B. Oude Lansink, 5 Ewout J. N. Groen, 1 Fay-Lynn Asselman, 1 Renske I. Wadman 1,† and W. Ludo van der Pol 1† † These authors contributed equally to this work. Nusinersen (Spinraza®) improves survival of infants with hereditary proximal spinal muscular atrophy and motor function in chil- dren up to 12 years. Population-based assessments of treatment effcacy are limited and confned to select cohorts of patients. We per- formed 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 effcacy (P < 0.01). Sixteen children (23%) achieved new motor milestones. Bulbar and respiratory function did not improve signif- cantly during treatment. In 15 patients from whom treatment-naïve data were available, the pre-treatment trajectory of motor func- tion 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 ob- serve improvement of respiratory and bulbar functions. 1 Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands 2 Biostatistics and Research Support, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, 3584 CX, Utrecht, The Netherlands 3 Child Development and Exercise Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands 4 Pediatric Intensive Care Unit, Wilhelmina Children’s Hospital, 3584 EA, Utrecht, The Netherlands 5 Department of Rehabilitation, Physical Therapy Science and Sports, UMC Utrecht Brain Center, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands Correspondence to: W. Ludo van der Pol University Medical Centre Utrecht Heidelberglaan 100, 3584 CX, Utrecht Received January 27, 2022. Revised August 17, 2022. Accepted October 27, 2022. Advance access publication October 31, 2022 © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. 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. Downloaded from https://academic.oup.com/braincomms/article/4/6/fcac269/6783135 by guest on 19 January 2023