Neuraminidase inhibitors and single dose baloxavir are effective and safe in uncomplicated influenza: a meta-analysis of randomized controlled trials.

ABSTRACT

BACKGROUND: Scarce evidence verifying the clinical impact of baloxavir on influenza complications is found. METHODS: PubMed, Cochrane Library, and Web of Science databases were searched through December 2020. Randomized-controlled trials (RCT) that enrolled patients with laboratory-confirmed influenza receiving neuraminidase inhibitors (NAI) or baloxavir comparing to placebo were assessed. PROSPERO Registration-number CRD42021226854. RESULTS: Twenty-one RCTs (11,697 patients) were included. Antiviral administration significantly reduced time to clinical resolution (mean difference -21.3 hours) and total influenza-related complications (OR0.55, 95%CI 0.42-0.73). Specifically, antivirals significantly decreased bronchitis (OR0.54, 95%CI 0.38-0.75), sinusitis (OR0.51, 95%CI 0.33-0.78), acute otitis media (OR0.48, 95%CI 0.30-0.77), and antibiotic prescription (OR0.62; 95%CI 0.48-0.80). A positive trend favored antivirals administration to reduce pneumonia (OR0.47, 95%CI 0.16-1.33), or hospitalization rates (OR0.65; 95%CI 0.34-1.24) compared to placebo, but did not reach statistical significance. Adverse events (AE) were reported in 11%, 8.9%, and 5.1% of NAIs, placebo and baloxavir recipients, respectively. Compared with NAIs, administration of baloxavir showed non-significantly reduced AEs (OR0.74, 95%CI 0.53-1.04). CONCLUSIONS: Single-dose baloxavir and NAIs were superior to placebo to reduce complications in uncomplicated influenza, with 40% significant reduction in antibiotic prescription. Safety and efficacy of single-dose baloxavir were non-inferior to NAIs.