Effect of Nusinersen on Respiratory Function in Paediatric Spinal Muscular Atrophy: 3 Year Follow-up

Abstract

Introduction/Aim: The first year of nusinersen treatment saw reduced lung function (LF) decline and improvement in Apnoea- Hypopnoea Indices (AHI). To determine if the respiratory muscle effects of nusinersen are maintained and describe the longerterm trajectory in LF and AHI in children with nusinersen treated Spinal Muscular Atrophy (SMA). Methods: A three-year prospective observational cohort study of paediatric SMA type 1-3 who began nusinersen in Queensland, Australia from June 2018 was conducted. During the study period clinical data was collected including respiratory deterioration events, and treatment with Non-Invasive Ventilation (NIV). Study protocol included clinical tests done prior to and during study: peripheral muscle strength testing, Spirometry, Forced Oscillation Technique, Sniff Nasal Inspiratory Pressure, Mean Inspiratory/Expiratory Pressure, Peak Cough Flow, Multiple Breath Washout, full diagnostic Polysomnography (PSG). LF and clinical data for two years prior to nusinersen commencement was collected retrospectively. Baseline and three-year LF and PSG parameters were compared. Results: Included 29/32 children commencing nusinersen (15 males; 0.4-17.3 years). For children with type 1 AHI improved. It remained stable in other types, as did the LF (see table 1). Peripheral muscle function testing remained stable. Two children with type 1 and one with type 3 had normalisation of PSG parameters, being able to wean from nocturnal NIV use. This differs from expected natural history, especially in type 1. Over course of study, four children with SMA type 1 and one child with SMA type 2 required respiratory related hospitalisations for either viral pneumonitis/presumed aspiration pneumonia. Conclusion: Over three years, children with SMA treated with nusinersen demonstrate stable LF and AHI in type 2 and 3 and improved AHI in type 1. Larger multicentre studies are required to further characterise changes. (Table Presented).