Adherence, Persistence, and Safety of Risdiplam in Spinal Muscular Atrophy: A Population-Based Cohort Study.

Abstract

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder caused by biallelic SMN1 variants, partially modulated by SMN2 copy number. Risdiplam, an oral SMN2 splicing modifier, has demonstrated efficacy in SMA. However, long-term adherence and persistence are key to sustaining benefit. We evaluated real-world adherence, persistence, and safety of risdiplam in a population-based cohort. This was a retrospective observational study including all genetically confirmed SMA type 1-3 patients treated with risdiplam in Spain between January 2020 and October 2025. Adherence was assessed using the proportion of days covered (PDC) from pharmacy dispensing records and the Morisky-Green questionnaire. Persistence was defined as time to permanent discontinuation or switch. Adverse events (AEs) were extracted from clinical records, and Kaplan-Meier analysis was used to estimate persistence probabilities. Fifty-three patients were included (38 adults, 15 pediatric patients); 5.7% had SMA type 1, 52.8% type 2, and 41.5% type 3. One pediatric patient with SMA type 1 was presymptomatic at treatment initiation. Median age at risdiplam initiation was 29 years (interquartile range [IQR] 17-42), and 35.8% had prior nusinersen exposure. Adherence was high: median PDC was 100% (IQR 100-100) at 12 months and throughout follow-up; all patients assessed with the Morisky-Green questionnaire (35/53, 66%) were adherent. At 12 months, 92.5% (49/53) remained on treatment (Kaplan-Meier estimate 94.3%; 95% CI 88.3-100.0). Persistence at 24 and 36 months was 87.8% and 80.1%, respectively; later estimates should be interpreted cautiously because of the limited number of patients at risk. Median treatment duration was 28.1 months. Nine patients (17.0%) discontinued treatment. Treatment-related AEs occurred in 4/53 patients (7.5%), including one pediatric case of leukocytoclastic vasculitis requiring permanent discontinuation. In this real-world population-based cohort, risdiplam showed very high adherence, favorable short- to mid-term persistence, and a favorable safety profile, supporting the feasibility of oral therapy in both pediatric and adult patients with SMA. Spinal muscular atrophy is a rare disease that leads to progressive muscle weakness and affects both children and adults. Risdiplam is an oral treatment that can be taken at home, which may be more convenient than other options that require repeated hospital visits or invasive procedures. In this study, we examined how well patients followed this treatment and how long they continued taking it in everyday clinical practice at a specialized center. We included a broad group of patients and followed them over time to better understand how the treatment performs outside clinical trials. We found that most patients took the medication consistently and continued treatment for prolonged periods. Only a small number stopped treatment, mainly due to side effects, lack of perceived benefit, or personal decisions. Overall, the treatment was well tolerated, with most side effects being mild, although one patient experienced a serious skin reaction that required discontinuation of treatment. These findings suggest that risdiplam is a practical long-term option in real-life settings, particularly because it can be taken at home. They also highlight that continuing treatment over time may reflect how patients and clinicians perceive its benefits and risks in daily practice.