Impact of nusinersen on respiratory progression in paediatric patients with spinal muscular atrophy type 2 and non-ambulant type 3

Nusinersen treatment provides significant functional motor benefit in the chronic forms of spinal muscular atrophy (SMA). Less is known on respiratory outcomes in nusinersen treated patients. Only short-term results on forced vital capacity (FVC) have been reported in heterogeneous treated SMA cohorts. Aim of this study is to evaluate the impact of nusinersen on respiratory function across the iSMAC international cohort of paediatric SMA2 and non-ambulant SMA3 patients (Italian SMA network, US PNCR, UK SMA REACH) when compared to the natural history data (NH) recently published by the consortium. Five-year retrospective study of SMA2 and non-ambulant SMA3 children (age 5-16years) treated with nusinersen within iSMAc centres. We collected lung function expressed as Forced vital capacity absolute and %predicted (FVC %pred), use of non-invasive ventilation (NIV) and cough device. Data was available for 100 patients 81 SMA2, 19 SMA3. Mean (SD) age at first injection was 8(3.3) and 9.4(3.8) years in SMA2 and 3 respectively. Mean disease duration prior to treatment was 7.1(3.3) and 7.3(3.9) years. At first injection 34/65(52%) SMA2 and 2/19 SMA3(11%) were on NIV; 49/65 (75%) SMA2 and 6/20(30%) SMA3 used cough devices. Mean FVC%pred (SD) at first treatment was 53.9(25.8) and 80.6(12.0) respectively. Up to age 13 years, when the respiratory decline is steeper, in treated SMA2 FVC% declined by 2.2%/year vs 4.2% NH, in treated SMA3 FVC% declined by 1.4% vs 6.3%. In the few patients older than 13 years (13 SMA2, 7 SMA3), a clear treatment effect was not detected. One year post treatment 4/36 patients were weaned off NIV, whilst 7, who were self-ventilating at baseline, were established on NIV. This study on the largest cohort of chronic SMA reported so far, confirms the positive role of nusinersen in delaying the respiratory decline in paediatric patients with SMA2 and non-ambulant SMA3 younger than 13 years when compared to natural history. Larger cohorts and longer observation are required to evaluate the role of nusinersen on older patients. F. Trucco, H. Weststrate, D. Ridout, M. Scoto, A. Rohwer, G. Coratti, M. Main, M. Pane, S. Messina, A. D'Amico, C. Bruno, D. De Vivo, B. Darras, J. Day, G. Baranello, V. Sansona, E. Bertini, R. Finkel, E. Mercuri, F. Muntoni, P.112 Impact of nusinersen on respiratory progression in paediatric patients with spinal muscular atrophy type 2 and non-ambulant type 3, Neuromuscular Disorders,Volume 32, Supplement 1,2022,Page S89,ISSN 0960-8966, https://doi.org/10.1016/j.nmd.2022.07.197. (https://www.sciencedirect.com/science/article/pii/S0960896622003996)