A meta-analysis showed that baloxavir shortened duration of nonsevere flu by one day and oseltamivir reduced it by 0.75 days; drug resistance and adverse events also occurred.

The US Centers for Disease Control and Prevention recommends antivirals for managing influenza in patients with severe illness or those at excess risk for complications. In a meta-analysis of 73 randomised clinical trials, investigators examined use of antivirals for those with nonsevere influenza (median age, 35 years). The study considered illness duration, hospitalisation, mortality, adverse events and emergence of resistance.

In 65 of the trials, treatment was initiated within two days of symptom onset. Time to alleviation of symptoms was shortened by one day and 0.75 days for baloxavir and oseltamivir, respectively. Oseltamivir (but not baloxavir) was associated with an increase in treatment-related adverse events. Drug resistance emerged in about 10% of baloxavir recipients (data were inconclusive for oseltamivir). Antivirals had no apparent effects on mortality in all patients, and on hospitalisation in those at low risk for complications. In patients at high risk for complications, baloxavir was associated with greater reduction in hospitalisation than oseltamivir (16 per 1000 compared with four per 1000 fewer hospitalisations), but statistical significance was not reached. 

Comment: The trials underlying this meta-analysis enrolled mostly younger adults, in whom hospitalisation was uncommon; thus, even with data pooling, uncertainty persists around that outcome. Importantly, the findings point to emergence of drug resistance (baloxavir) and risk for adverse events (oseltamivir), which must be balanced against limited benefit for the average patient. Editorialists also note the issue of drug cost. Nevertheless, these treatments yielded numerical decreases in length of illness – so until a well-powered study shows otherwise, antiviral treatment should be given to patients with nonsevere influenza who are at risk for severe disease.

Hana M. El Sahly, MD, Professor of Molecular Virology and Microbiology and Infectious Diseases and Investigator at the Vaccine Research Center, Baylor College of Medicine, Houston, USA.

Gao Y, et al. Antiviral medications for treatment of nonsevere influenza: a systematic review and network meta-analysis. JAMA Intern Med 2025 Jan 13; e-pub (https://doi.org/10.1001/jamainternmed.2024.7193).

Baghdadi JD, et al. The limited role for antiviral therapy in influenza. JAMA Intern Med 2025 Jan 13; e-pub (https://doi.org/10.1001/jamainternmed.2024.7258).

This summary is taken from the following Journal Watch title: Infectious Diseases.