Real-world 12-month outcomes of Risdiplam in spinal muscular atrophy types 2 and 3: A Brazilian cohort

INTRODUCTION: Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by progressive axial and proximal limb weakness, often leading to ventilatory insufficiency. Risdiplam, an oral SMN2 splicing modifier, has demonstrated efficacy across clinical trials involving both infantile and late-onset SMA. However, real-world data on its long-term safety and effectiveness remain limited. OBJECTIVE: To evaluate the safety and preliminary efficacy of Risdiplam after one year of treatment in patients with SMA types 2 and 3. METHODS: This retrospective, single-center study included patients with genetically confirmed SMA treated with Risdiplam at the Neuromuscular Clinic of the Hospital das Clínicas, University of São Paulo, Brazil. All participants were treatment-naïve before initiating Risdiplam and were followed for 12-months. Motor function (CHOP-INTEND, HFMS), pulmonary function (FVC, FEV₁), and necessity of G-tube were assessed at baseline, 6 m, and after one year of therapy. RESULTS: Sixteen patients were included (mean age 20-years, range 6-56). Eleven patients (69%) had SMA type 2, while 5 (31%) had SMA type 3. The mean untreated disease duration was 18-years (range 5-44). After 12-months, 13-patients (81%) showed apparent stabilization or improvement in motor function, while 3 (19%) exhibited motor decline. Pulmonary function improved or stabilized in 13 patients (81%) and declined in 3 (19%). Clinical decline was observed in patients with progressive scoliosis or overweight. All patients maintained exclusive oral feeding. CONCLUSION: Preliminary data from the one-year follow-up suggest that Risdiplam is safe and appears generally effective in preserving or enhancing motor, respiratory, and swallowing functions. Patients with severe skeletal deformities exhibited less favorable outcomes.