The Incidence Of Adverse Reactions In Patients With Spinal Muscular Atrophy Treated With Nusinersen: A Meta-analysis

Objective:According to meta-analysis to understand the occurrence of adverse effects and the factors affecting them in patients with spinal muscular atrophy treated with Nusinersen.Methods:Nusinersen/Nusinersen sodium and safety,side effects,adverse reactions,adverse events,side effects were retrieved in the databases of China Knowledge Network(CNKI),Wanfang Database,Vipers Database(VIP),China Biomedical Literature Database(CBM),Pub Med,Embase,Cochrane Library,and the last search was conducted in February 2023.After screening the literature according to the established inclusion and exclusion criteria,the full text was read in detail and valid data were extracted,Stata 17 software was applied to weight and combine the adverse reactions of the literature that met the inclusion criteria.Results:18 articles were ultimately included in this study,and a total of 993 study subjects had information about the total incidence of adverse reactions,of which 531 had adverse reactions.The included literature was generally well designed with complete reporting of results.Meta-analysis showed an overall adverse reaction rate of 75%(95%CI:57%-90%)for Nusinersen,and the 10 most frequent adverse reactions were fever(50%,95% CI:24%-75%),cough(48%,95% CI:23%-74%),nasal congestion(35%,95% CI:24%-48%),upper respiratory infection(33%,95%CI:15%-54%)headache(32%,95%CI : 18%-48%),pneumonia(29%,95%CI : 10%-52%),nasopharyngitis(27%,95%CI:4%-59%),vomiting(25%,95%CI:11%-42%),diarrhea(25%,95%CI:18%-33%),and constipation(17%,95% CI : 3%-38%).The incidence of adverse reactions in randomized and clinical trials in the subgroup analysis was high at 96%(95% CI: 93%-98%),while the incidence of adverse reactions in cohort studies was relatively low at 63%(95% CI: 43%-81%).Among the different clinical types,the incidence of adverse reactions in patients with infantile-onset spinal muscular atrophy was 88%(95% CI: 41%-100%),and the highest incidence was fever at 57%(95% CI:16%-92%),followed by constipation at 34%(95% CI: 26%-43%);The incidence of adverse reactions in patients with later-onset spinal muscular atrophy was 82%(95% CI:56%-98%),with the highest incidence of headache at 41%(95% CI:23%-61%).The incidence of adverse reactions was 98%(95% CI: 95%-100%)in SMA patients ≤2 years old,88%(95% CI: 64%-100%)in SMA patients 2-16 years old,and66%(95% CI: 33%-93%)in SMA patients ≥16 years old.Comparing adverse reactions in SMA patients aged ≤2 years and 2-16 years,the incidence of fever(75%vs.28%),pneumonia(29% vs.13%),vomiting(30% vs.22%),and upper respiratory tract infection(42% vs.29%)was found to decrease with age,while no change was observed in the incidence of cough(30% vs.30%).Comparing adverse effects in SMA patients aged 2-16 years and≥16 years,the incidence of headache(33% vs.57%)was found to increase with age,and the incidence of low back pain(25% vs.21%)was similar.The incidence of adverse reactions was 78%(95% CI: 37%-100%)in SMA patients with study duration ≤ 1 year,79%(95% CI: 52%-97%)in SMA patients with study duration 1-2 years,and 69%(95% CI: 24%-99%)in SMA patients with study duration ≥ 2 years.Comparing adverse effects in SMA patients with study duration ≤1 year and 1-2 years,the incidence of headache(55% vs.32%),low back pain(28%vs.17%),nausea(25% vs.6%),and upper respiratory tract infection(39% vs.19%)was found to decrease with increasing study duration.Conclusion:High incidence of adverse reactions in patients with spinal muscular atrophy treated with Nusinersen,infantile-onset spinal muscular atrophy patients are commonly affected by respiratory(upper respiratory tract infection,cough,pneumonia)adverse reactions,which are considered to be related to the progression of spinal muscular atrophy disease,and patients with later-onset spinal muscular atrophy had a higher incidence of adverse events with headache,low back pain,and vomiting,which may be associated with complications of lumbar puncture considering the intrathecal administration of Nusinersen.Age and length of study(cumulative dose)were negatively associated with the incidence of adverse reactions.