Risdiplam Impact in Treatment Naïve and Non-Naïve Pediatric and Adult Patients With Spinal Muscular Atrophy

Abstract

Background: Risdiplam, an oral disease-modifying therapy, has demonstrated safety and efficacy in clinical trials, but real-world data from Asia are limited. Methods: This prospective study followed 34 symptomatic SMA patients (24 adults, 10 children) over 36 months of risdiplam treatment. The cohort included 5 patients with SMA type 1, 25 with SMA type 2, and 4 with SMA type 3, with ages ranging from 6.9 to 50.9 years. Most (91%) were wheelchair users, and 74% had scoliosis managed by bracing or spinal surgery. Twenty-five patients (22 adults, 3 children) were treatment naïve, and 9 patients (2 adults, 7 children) switched from nusinersen. Motor function was assessed at baseline, 6, 12, 24, and 36 months using MFM-32, RULM, ATEND, and HFMSE. In pediatric patients, HRQOL was evaluated using PedsQL Neuromuscular Module and PedsQL Generic Core scale. HRQOL of their parents was assessed with PedsQL Family Impact Module. Results: After 36 months, MFM-32 score was significantly improved in those switching therapies [p = 0.042], while both MFM-32 and RULM scores were significantly improved in treatment-naïve group [p = 0.005 and p = 0.043]. Parents experienced HRQOL gains in their Physical domain (2 years: PedsQL Family Impact Module, p = 0.038). Pediatric patients showed improvement in the Communication domain (3 years: PedsQL Neuromuscular Module, p = 0.042). Risdiplam was generally well tolerated; however, two adults discontinued due to adverse effects. Moreover, two adult patients died during treatment. Conclusions: This study fills Asian real-world data gaps, stresses the importance in monitoring in severe SMA, and underscores the need for larger, long-term safety and efficacy studies.