The Effect of Disease-Modifying Therapies on Lung Function and Respiratory Muscle Strength in Spinal Muscular Atrophy: Systematic Review and Meta-Analysis

Abstract

Background: Spinal muscular atrophy (SMA) is often complicated by respiratory problems. The disease-modifying therapies (DMTs) (nusinersen, onasemnogene abeparvovec, and risdiplam) have improved survival, motor function, and functional muscle strength in patients with SMA, but their effects on lung function and respiratory muscle strength need further clarification. Therefore, we performed a systematic review of studies that documented the effects of DMTs on lung function and respiratory muscle strength in patients with SMA types I, II, III, and IV. Methods: We searched the electronic databases PubMed/MEDLINE, CINAHL, Embase, and Web of Science up to December 2023. We included pre-post studies that determined the effect of DMTs for SMA on lung function or respiratory muscle strength in patients with SMA. Where possible, we performed a meta-analysis using a random-effects model with generic inverse variance weighing. Results: We included 19 studies of 376 identified records (16 longitudinal cohort studies and 3 case series) with 384 participants. Seventeen studies investigated the effect of nusinersen, and two studies investigated the effect of risdiplam. Seventeen studies had a moderate and two had a high risk of bias. Most of these studies did not report statistically significant improvement in lung function or respiratory muscle strength after treatment with nusinersen or risdiplam. A meta-analysis of 13 studies showed no statistically significant improvement in FVC after 2, 6, 10, and > 12 months of treatment with nusinersen. Conclusions: The findings of this review indicate that there is moderate evidence that nusinersen does not improve FVC, FEV₁, peak expiratory flow, or maximum inspiratory pressure in subjects with SMA types I, II, III, or IV. There was no statistically significant decline in lung function and respiratory muscle strength after treatment. This may suggest that nusinersen may have stabilized lung function and respiratory muscle strength.

Keywords: disease-modifying therapies; lung function; meta-analysis; nusinersen; respiratory muscle strength; risdiplam; spinal muscular atrophy; systematic review.