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 (OR:0.55, 95%CI: 0.42–0.73). Specifically, antivirals significantly decreased bronchitis (OR:0.54, 95%CI: 0.38–0.75), sinusitis (OR:0.51, 95%CI: 0.33–0.78), acute otitis media (OR:0.48, 95%CI: 0.30–0.77), and antibiotic prescription (OR:0.62; 95%CI: 0.48–0.80). A positive trend favored antivirals administration to reduce pneumonia (OR:0.47, 95%CI: 0.16–1.33), or hospitalization rates (OR:0.65; 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 (OR:0.74, 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.

KEYWORDS:

• Baloxavir marboxil
• influenza
• neuraminidase inhibitors
• oseltamivir
• peramivir
• zanamivir

Acknowledgments

This study was part of the doctoral thesis from ST at Medicine Department, University of Barcelona, Spain.

Declaration of interest

J. Rello has declared serving as a consultant and received grant support from Genentech and ROCHE. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

J. Rello and S. Tejada did the study design. S. Tejada and Y. Peña-López did the literature search and collected the data. J. Rello and X. Corbella validated the data. S. Tejada and C.G. Forero analyzed the data and did the quality assessment. J. Rello, S. Tejada, and A. Tejo wrote the first draft of the manuscript. All authors interpreted the data, revised, and approved the manuscript submission.

Supplementary material

Supplemental data for this article can be accessed here.

Article Highlights

• 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 was non-inferior to NAIs.

Additional information

Funding

This work was funded by CIBERES, Instituto de Salud Carlos III, Madrid, Spain (Fondos FEDER) (CB06-06-036).