Effectiveness of Nusinersen in Adolescents and Adults with Spinal Muscular Atrophy: Systematic Review and Meta-analysis.

Abstract

Nusinersen clinical trials have limited data on adolescents and adults with 5q-associated spinal muscular atrophy (SMA). We conducted a systematic literature review (SLR) and meta-analysis to assess effectiveness of nusinersen in adolescents and adults with SMA in clinical practice. Our search included papers published 12/23/2016 through 07/01/2022 with≥5 individuals≥13years of age and with≥6months' data on≥1 selected motor function outcomes [Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), and Six-Minute Walk Test (6MWT)]. For meta-analysis, effect sizes were pooled using random-effects models. To understand treatment effects by disease severity, subgroup meta-analysis by SMA type and ambulatory status was conducted. Fourteen publications including 539 patients followed up to 24months met inclusion criteria for the SLR. Patients were age 13-72years and most (99%) had SMA Type II or III. Modest improvement or stability in motor function was consistently observed at the group level. Significant mean increases from baseline were observed in HFMSE [2.3 points (95% CI 1.3-3.3)] with 32.1% (21.7-44.6) of patients demonstrating a clinically meaningful increase (≥3 points) at 18months. Significant increases in RULM were consistently found, with a mean increase of 1.1 points (0.7-1.4) and 38.3% (30.3-47.1) showing a clinically meaningful improvement (≥2 points) at 14months. Among ambulatory patients, there was a significant increase in mean 6MWT distance of 25.0m (8.9-41.2) with 50.9% (33.4-68.2) demonstrating a clinically meaningful improvement (≥30m) at 14months. The increases in HFMSE were greater for less severely affected patients, whereas more severely affected patients showed greater improvement in RULM. Findings provide consolidated evidence that nusinersen is effective in improving or stabilizing motor function in many adolescents and adults with a broad spectrum of SMA.