Lung Function and Respiratory Muscle Strength in Symptomatic Children and Adults With Spinal Muscular Atrophy Treated With Nusinersen

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) causes progressive muscle weakness. Respiratory muscle weakness results in progressive lung function decline, scoliosis, and chest wall deformities that predispose to respiratory failure. The efficacy of survival motor neuron protein-augmenting therapies on motor function in patients with SMA has been reported extensively, but how respiratory function changes under treatment remains underexplored. The aim of this study was to evaluate longitudinal changes in lung function and respiratory muscle strength during nusinersen treatment.

METHODS: We conducted a national retrospective observational cohort study at the University Medical Center Utrecht. We included children and adults with SMA types 1, 2, and 3a, who symptomatically started treatment with nusinersen between May 2017 and July 2025 as part of the Dutch reimbursement arrangements. We retrieved all available data on lung function and respiratory muscle strength collected during routine care. We analyzed the differences in the annual rates of change of lung function and respiratory muscle strength before and after nusinersen treatment initiation, using linear mixed-effects models.

RESULTS: We included 120 patients (60 female individuals, 50%), of whom 78 were children (median age 7.3 years, range 0.7, 17.7) and 42 adults (median age 34.4 years, range 18.1, 76.1) at nusinersen initiation. In children, we observed a slower decline in lung function and a higher expiratory muscle strength after starting nusinersen. The absolute mean slope differences were 4.1% (95% CI 2.2-6.0) for forced vital capacity, 3.8% (95% CI 1.4-6.2) for forced expiratory volume in 1 second (FEV 1), 4.2% (95% CI 0.3-8.0) for peak expiratory flow, and 5.1% (95% CI 0.7-7.6) for maximal expiratory pressure after initiation of nusinersen. In adults, we only observed a change in FEV 1 after starting nusinersen. At treatment initiation, 30 patients required ventilatory support. None were able to discontinue ventilation, and 6 patients started noninvasive ventilation during treatment.

DISCUSSION: This large retrospective cohort study found slower deterioration of lung function in symptomatic children during nusinersen treatment and improvements in respiratory muscle strength. In adult patients treated with nusinersen, we only observed a change in FEV 1.

CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that nusinersen slows deterioration of lung function and improves respiratory muscle strength in symptomatic children with SMA.