Neuraminidase inhibitors are effective and safe in reducing influenza complications: meta-analysis of randomized controlled trials

Background: There is scarce evidence verifying the impact of neuraminidase inhibitors (NAIs) in reducing influenza complications. The aim was to evaluate the available evidence from randomized-controlled trials (RCT) regarding the efficacy and safety of NAIs in reducing influenza complications. Methods: A systematic search of the literature was performed in the Cochrane Library, PubMed and Web of Science databases (2006-2019). Eligibility criteria were RCT that enrolled patients of any age or clinical severity with seasonal influenza (H1N1, H3N2, or B) or influenza-like syndrome and receiving NAIs comparing to placebo therapy. Results: Eighteen RCTs (9004 patients) were included: nine focused on oral oseltamivir, six on inhaled zanamivir, and three on intravenous peramivir. Administration of NAIs therapy significantly decreased the time to clinical resolution (median difference:-17.7 hours; and total influenza-related complications (OR: 0.64, 95%CI: 0.51-0.82). In addition, NAIs significantly decreased acute otitis media complication (OR: 0.50, 95%CI: 0.31-0.82) and need for antibiotic treatment (OR: 0.64, 95%CI: 0.46-0.90); and showed a trend towards a reduced occurrence of pneumonia (OR: 0.44, 95%CI: 0.10-2.00), bronchitis (OR: 0.80, 95%CI: 0.43-1.48), sinusitis (OR: 0.73, 95%CI: 0.40-1.32), asthma exacerbations (OR: 0.57, 95%CI: 0.28-1.16), and hospitalizations (OR: 0.57, 95%CI: 0.24-1.38). The overall proportion of AEs tend to increase with NAIs treatment (OR: 1.16, 95%CI: 0.92-1.47). Use of NAIs was associated with a significant increase of nausea and vomiting (OR: 1.61, 95%CI: 1.04-2.50) and a decrease on diarrhea (OR: 0.81, 95%CI: 0.65-1.00). Conclusions: NAIs are effective in reducing time to clinical resolution, total influenza-related complications, otitis media, and need of antibiotic administration. Reductions on mortality, pneumonia, asthma exacerbations or hospitalization rates only did demonstrate a trend benefit in favor of NAIs. The only significant AE is the increased occurrence of nausea and vomiting.