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), on asemnogene abeparvovec, and risdiplam (RIS). There are no comparative studies for treatments to date. Aim: To present Queensland, Australia's experience with NUS and RIS. Methods: An observational study of all children changing from NUS to RIS when RIS became available in Australia (2021). Polysomnography (PSG)/Respiratory Function Tests (RFT) were performed: annually beginning prior to NUS commencement; and prior to and at 3, 12 months from RIS commencement. Results: Seven children changed from NUS to RIS (age range 3.1-18.9 years old [median 13.7y.o]). Reasons included: difficulties with NUS administration (lumbar puncture access, travel to hospital, psychosocial). Four children were excluded due to lack of lung function (RFT)/polysomnography (PSG) data. Patient 1: 7.8y.o boy with SMA type 2 diagnosed at 1.1years. NUS commenced at 3.5, changed to RIS at 7.8 years. Nocturnal NIV was commenced for sleep disordered breathing (SDB) at 1.1 years post-NUS, ceased 3.0 post NUS, but recommenced 1.0 years post RIS; 2 admissions for lower respiratory tract infections (LRTIs)Patient 2: 15.5yo female with type 2 diagnosed at 1.4 years. NUS commenced at 6.0, changed to RIS at 15.3 years. Nocturnal NIV commenced for SDB prior to NUS treatment and continues; 5 LRTIs admissions. Patient 3: 15.8y.o male diagnosed SMA type 3 at 1.8 years of age. NUS commenced at 12.7, changed to RIS at 15.8 years of age. He does not require nocturnal NIV; 1 LRTI admission. See figure 1 for PSG findings. 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/RFT findings of 3 children commenced on NUS, and changed to RIS. Two children had increases in AHI, with one 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 too late 3. Treatment effectiveness may vary between DMT in specific cohorts/overall. 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 available DMT.