Children with spinal muscular atrophy treated with nusinersen/risdiplam

Abstract

Introduction: Respiratory morbidity and survival have improved in Spinal Muscular Atrophy (SMA) [especially type 1] with disease modifying treatments (DMTs): nusinersen (NUS), onasemnogene abeparvovec, and risdiplam (RIS). There are no comparative studies for treatments to date. Aim: To present Queensland's experience (Queensland Children's Hospital [QCH]) with NUS and RIS Methods: An observational study of all children changing from NUS to RIS when RIS became available in Australia on pharmaceutical benefits scheme (2021). Polysomnography (PSG) and Respiratory Function Tests (RFT) were performed: annually beginning prior to NUS commencement; and prior to and at 3 and 12 months from RIS commencement. Results: Seven children changed from NUS to RIS (age range 3.1-18.9 y.o [median 13.7 y.o]). Reasons included: difficulties with NUS administration (lumbar puncture access, travel to QCH, psychosocial). Four children were excluded from this report due to lack of lung function (RFT)/polysomnography (PSG) data. Characteristics of 3 children are presented in table 1. While patient 1's FVC declined 10% predicted, 2 and 3 remained stable. All three participants had declining PSG indices; Patient 1 had ceased nocturnal NIV post-NUS, however restarted once on RIS. Conclusion: This is the first report of real-world PSG and RFT findings of 3 patients commenced on NUS, later changed to RIS. Two of 3 patients had declining central apnoea indices on PSG, with one patient also demonstrating a clinically significant decline in FVC and restarted nocturnal ventilation with RIS treatment. Postulated reasons for decline include: 1. Mechanism of action of RIS is still debated; 2. Timing of RIS commencement may be too late 3. Treatment effectiveness may vary between DMT in specific cohorts/overall. The advantage of RIS is its oral administration. Further DMT comparative studies need to be undertaken to better understand efficacy of each treatment and which cohorts may receive the most benefit from each of the available DMT.