Adverse events in the treatment of spinal muscular atrophy in children and adolescents with nusinersen: A systematic review and meta-analysis

Abstract

ObjectivesTo systematically analyze adverse events (AEs) in treatment of spinal muscular atrophy (SMA) with Nusinersen in children and adolescents.MethodsThe study is registered on PROSPERO (CRD42022345589). Databases were searched and literature relating to Nusinersen in the treatment of spinal muscular atrophy in children from the start of database establishment to December 1, 2022, was retrospectively analyzed. R.3.6.3 statistical software was used, and random effects meta-analysis was performed to calculate weighted mean prevalence and 95% confidence intervals (CI).ResultsIn total, 15 eligible studies were included, with a total of 967 children. Rate of definite Nusinersen-related AEs was 0.57% (95% CI: 0%–3.97%), and probable Nusinersen-related AEs 7.76% (95% CI: 1.85%–17.22%). Overall rate of AEs was 83.51% (95% CI: 73.55%–93.46%), and serious AEs 33.04% (95% CI: 18.15%–49.91%). For main specific AEs, fever was most common, 40.07% (95% CI: 25.14%–56.02%), followed by upper respiratory tract infection 39.94% (95% CI: 29.43%–50.94%), and pneumonia 26.62% (95% CI: 17.99%–36.25%).The difference in overall AE rates between the two groups (Nusinersen group and placebo group) was significant (OR = 0.27,95% CI: 0.08–0.95, P = 0.042). Moreover, incidence of serious adverse events, and fatal adverse events were both significantly lower than in the placebo group (OR = 0.47, 95%CI: 0.32–0.69, P < 0.01), and (OR = 0.37, 95%CI: 0.23–0.59, P < 0.01), respectively.ConclusionNusinersen direct adverse events are rare, and it can effectively reduces common, serious, and fatal adverse events in children and adolescents with spinal muscular atrophy.

Spinal Muscular Atrophy: An Evolving Scenario through New Perspectives in Diagnosis and Advances in Therapies

“…Nusinersen has been associated with several adverse events, with the majority being pyrexia, upper respiratory tract infections, nasopharyngitis, vomiting, headache, and constipation. Serious adverse events were also reported, which were in line with the typical nature and frequency of events observed in the context of SMA or during lumbar puncture procedures [22,68]. In the past, a variety of side effects have been identified for different antisense oligonucleotides (ASOs).…”

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

“… 64 65 66 A systematic review and meta-analysis of adverse events in treating SMA with nusinersen was published recently. 67 Data from 969 children and adolescents was analyzed. The overall rate of adverse events was 83.51%, and serious adverse events were 33.04%.…”

“…The incidence of severe and fatal adverse events was significantly lower than in the placebo group. 67 …”

“…The incidence of severe and fatal adverse events was significantly lower than in the placebo group. 67 A higher dose of nusinersen is being tested in patients with early and late-onset SMA (DEVOTE study). 68 In Part A, all six enrolled participants aged 6.1 to 12.6 years have completed the study.…”