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

backgroundRisdiplam, an oral disease-modifying therapy, has demonstrated safety and efficacy in clinical trials, but real-world data from Asia are limited.

methodsThis 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.

resultsAfter 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.

conclusionsThis 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.