Therapeutic Role of Nusinersen on Respiratory Progression in Pediatric Patients With Spinal Muscular Atrophy Type 2 and Nonambulant Type 3
Federica Trucco, Deborah Ridout, Harriet Weststrate, Mariacristina Scoto, Annemarie Rohwer, Giorgia Coratti, Marion Main, Anna Mayhew, Jacqueline Montes, Roberto De Sanctis, Marika Pane, Maria Carmela Pera, Valeria Sansone, Emilio Albamonte, Adele D’Amico, Claudio Bruno, Sonia S. Messina, Anne‐Marie Childs, Tracey Willis, Min Ong, Laurent Servais, Anirban Majumdar, Imelda Hughes, C. Marini-Bettolo, Deepak Parasuraman, Vasantha Gowda, Giovanni Baranello, Enrico Bertini, Darryl C. De Vivo, Basil T. Darras, John Day, Oscar H. Mayer, Zarazuela Zolkipli‐Cunningham, Richard S. Finkel, Eugenio Mercuri, Francesco Muntoni, for iSMAc
Abstract
Background and Objectives: Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020. Methods: This is a 5-year retrospective observational study of pediatric SMA type 2 and nonambulant type 3 (age ≤18 years) treated with nusinersen. The primary objective was to compare the slopes of decline in forced vital capacity % predicted (FVC% pred.), FVC, and age when FVC dropped below 60% between the treated patients and a control group from the natural history cohort. Data on peak cough flow and the use of noninvasive ventilation (NIV) and cough assist were collected. Results: = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up. Discussion: This study included the largest real-world cohort of pediatric patients with milder SMA types. The results suggest a positive role of nusinersen in delaying the respiratory decline in patients treated longer than 1 year when compared with natural history. Larger cohorts and longer observation are planned. Classification of Evidence: This study provided Class III evidence that nusinersen slows progression for patients with SMA types 2 and 3 compared with a natural history cohort.