Background: SMA1 is a rare genetic neuromuscular disease causing rapid deterioration of voluntary motor and bulbar function when untreated. Although several trials of SMA disease-modifying therapies have been conducted, limited evidence exists for associating post-treatment improvements in health outcomes to patient and/or caregiver health-related quality of life (HRQOL). This study assessed the health outcomes of symptomatic SMA1 infants treated with OA, a one-time gene replacement therapy.
Objective: We sought to assess health outcomes including pulmonary and nutritional interventions, swallow function, speaking ability, hospitalization rate, and motor function as indirect HRQOL-related measures for SMA1 patients treated with OA.
Methods: We conducted a pooled post-hoc analysis of symptomatic SMA1 infants (<6 months; two SMN2 copies) treated with OA in the START, STR1VE, and STR1VE-EU trials conducted between 12/2014 and 09/2020. Patients were followed for 18 to 24 months post-treatment. Results: This analysis included 65 patients. By study completion: 36 (55%) patients did not require noninvasive ventilation. 60/61 (98%) patients had stable or improved swallow function demonstrated by clinical swallowing assessment, and 49 (75%) fed exclusively by mouth; 26/27 (96%) patients were able to speak. Mean percentage of time hospitalized was 4.3%. Mean unadjusted annualized hospitalization rate was 1.6 (range=0–14), with a mean length of stay/hospitalization of 7.4 (range=2.0–20.5) days. 52 (80%) patients achieved full head control, 38 (58%) sat without assistance, and five (7.7%) patients walked independently. Conclusions: OA treatment of patients with symptomatic SMA1 preserves respiratory and bulbar function, reduces hospitalization and nutritional support requirements, and improves motor function. This contrasts with the natural history of progressive respiratory failure and early death. Reduction in respiratory interventions, hospital readmissions, preservation of bulbar function, and continued achievement of motor milestones might be associated with improved HRQOL. Reduced healthcare utilization and care requirements could potentially alleviate patient/caregiver burden, suggesting further HRQOL benefit.