Remaining Burden of Spinal Muscular Atrophy Among Treated Patients: A Survey of Patients and Caregivers.

Objective: Spinal muscular atrophy (SMA) significantly impacts motor function. This study aimed to assess the persistent burden and unmet needs among currently treated patients with SMA and their caregivers.

Methods: Two complementary web-based surveys were distributed in August 2024 among patients with SMA and their caregivers. Non-ambulant patients with SMA currently receiving risdiplam or nusinersen, and/or their primary, informal caregivers were eligible to participate. Survey modules captured clinical, humanistic, productivity, and caregiver-related burden of disease. The PROMIS Fatigue and EQ-5D-5L were used to assess fatigue and quality of life.

Results: 40 pediatric (mean age 8.3 years; represented by caregiver proxies) and 68 adult patients (mean age 37.5 years) were included, of which the majority were on SMN-targeted treatment for ≥ 2 years (82.5% and 94.1%, respectively), and nearly half were on treatment for ≥ 4 years. Despite continued treatment, muscle weakness was reported in 95% of pediatric and 100% of adult patients, with 63% of pediatric and 68% of adult patients reporting "severe" or "very severe" muscle weakness that substantially impacted motor function and performance of activities of daily living. Increased fatigue and muscle weakness were associated with worse overall health. Findings also demonstrated impacts of SMA on patient quality of life and well-being. Most participants reported mobility limitations and muscle weakness as being least improved by current treatment.

Interpretation: Despite the use of current treatments, there remains a significant burden of SMA on patients and their caregivers. Muscle weakness and mobility limitations remain key areas of unmet need.