Abstract
Evidence for nusinersen administration in adult 5q spinal muscular atrophy (5q-SMA) patients is scarce and based on real-world observational data. The present systematic review and meta-analysis aimed to explore the efficacy and safety of nusinersen in patients older than 12 years of age with 5q-SMA. We searched MEDLINE, EMBASE, the Cochrane Library, and grey literature through April 2021. Cross-sectional studies, case reports, review articles, and studies with follow-up less than 6 months were excluded. We included 12 records (seven case-series, five cohorts) representing 11 population cohorts and enrolling 428 SMA patients. We observed statistically significant improvements on motor function Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores at the longest follow-up assessments [SMD = 0.17(95% CI 0.01-0.33), SMD = 0.22(95% CI 0.06-0.38), respectively]. HFMSE and RULM significant improvements were also detected at the subgroup analysis during 10 and 14 months. HFMSE and RULM amelioration occurred earlier in patients with SMA type 3 or 4 during short-term analysis (≤ 6 months). 6-min walk tests (6MWT) and pulmonary function tests did not change. Minimal clinically important differences in HFMSE and RULM were observed in 43.3% (95% CI 34.5-52.3) and 38.9% (95% CI 27.7-50.7), respectively. Severe adverse events were reported in 2% (95% CI 0-5.8). Treatment withdrawal rate was 3% (95% CI 0.5-6.6). Despite the low quality of evidence and the unmet need for randomized data to establish the safety and efficacy of nusinersen in adults, our meta-analysis confirms that nusinersen is a valuable treatment option for older patients with longer-disease duration.Trial registration: PROSPERO database CRD42020223109.