Effectiveness and safety of neuraminidase inhibitors in reducing influenza complications: a meta-analysis of randomized controlled trials

Background: Several studies suggest that neuraminidase inhibitors (NIs) can reduce the duration of influenza symptoms. However, data regarding their effectiveness in reducing influenza complications are scarce. Methods: We evaluated the effectiveness of NIs in reducing influenza complications and mortality of patients with seasonal influenza, by performing a meta-analysis of randomized controlled trials (RCTs), retrieved from PubMed, Cochrane Central Register of Controlled Trials and Scopus databases, comparing NIs with placebo. Results: Eleven RCTs (10 double-blind) were included; 8 involved adults/adolescents. In total, 5315 patients were included; 3491 (65.7%) with confirmed infection. Total influenza-related complications were significantly less likely in otherwise healthy patients with confirmed influenza infection that were treated with NIs versus placebo [7 RCTs, 2621 patients, risk ratio (RR)=0.74, 95% confidence interval (CI)=0.58-0.95] This finding was more pronounced in high-risk patients [4 RCTs, 475 patients, RR=0.37, 95% CI=0.24-0.59]; P<0.01 for the chi(2) test for subgroup differences. In the comparisons regarding individual complications, a trend in favour of NIs was observed. Acute otitis media was significantly less likely in patients with confirmed influenza infection treated with NIs versus placebo (3 RCTs, 1124 patients, RR=0.50, 95% CI=0.30-0.85). No differences were found in the comparisons regarding the safety outcomes. No deaths were observed in trials that reported on mortality. Conclusions: NIs seem to be effective in reducing total influenza-related complications in otherwise healthy and high-risk patients, and have an acceptable safety profile. However, RCTs providing separate data for mild to serious complications and detailed reporting of adverse events and mortality are needed.