by Justin Jackson , Medical Xpress

Credit: Pixabay/CC0 Public Domain

A systematic review and meta-analysis led by Shandong University in China has evaluated the comparative efficacy and safety of antiviral medications for treating nonsevere influenza. Findings indicate that baloxavir may reduce hospital admission risks for high-risk patients and shorten symptom duration without increasing adverse events. One factor in distinguishing baloxavir from other antivirals in the study was the quality of the data reviewed.

Influenza is a viral respiratory disease that affects millions annually, with severe complications that can be fatal. Antiviral medications such as neuraminidase inhibitors, like oseltamivir (Tamiflu) and zanamivir (Relenza), and endonuclease inhibitors, such as baloxavir (Xofluza), are used to alleviate symptoms and reduce complications by targeting specific mechanisms of the influenza virus. Neuraminidase inhibitors block the virus’s ability to spread between cells, while endonuclease inhibitors prevent the virus from replicating its genetic material.

Finding the optimal treatment strategy for nonsevere influenza remains elusive due to mixed results from previous studies. To sift through the noise, many of those past studies were analyzed together.

In the meta-study, “Antiviral Medications for Treatment of Nonsevere Influenza: A Systematic Review and Network Meta-Analysis,” published in JAMA Internal Medicine, the team analyzed 73 randomized clinical trials involving 34,332 participants comparing direct-acting antiviral drugs, including baloxavir, oseltamivir, zanamivir, and others, against placebo or standard care.

Data sources included MEDLINE, Embase, CENTRAL, CINAHL, Global Health, Epistemonikos, and ClinicalTrials.gov. Data extraction and synthesis were performed independently by paired reviewers. A total of 73 trials met inclusion criteria, encompassing studies conducted between 1971 and 2023. Researchers assessed outcomes such as mortality, hospitalization, symptom alleviation, and adverse events.

The certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. This systematic method assesses the quality of evidence based on factors such as the risk of bias, consistency of results, directness of evidence, and precision of estimates. This framework helps determine the strength of the findings and their reliability for clinical decision-making.

Results showed that baloxavir likely reduces symptom duration by 1.02 days (moderate certainty) and may lower hospital admission risks for high-risk patients (low certainty). High-certainty evidence indicated that baloxavir has little or no effect on mortality for low-risk and high-risk patients.

Adverse events associated with baloxavir were lower than those associated with placebo (high certainty). However, baloxavir was linked to approximately 10% risk of resistance emergence (low certainty).

Oseltamivir showed little or no effect on mortality (high certainty) and hospital admission (high certainty) for both risk groups. The mean reduction in symptom duration was 0.75 days (moderate certainty). Moderate-certainty evidence suggests oseltamivir likely increases adverse events.

Other antivirals, including zanamivir, laninamivir, and umifenovir, demonstrated inconsistent or uncertain effects on key outcomes, with evidence quality varying from moderate to very low. Hospitalization data for peramivir and amantadine were unavailable.

Baloxavir emerged as a promising option for high-risk patients with nonsevere influenza, offering potential benefits in reducing hospitalization risk (low certainty) and symptom duration (moderate certainty) without increasing treatment-related adverse events (versus placebo). Findings also reinforce the limited effectiveness of oseltamivir in symptom alleviation and its association with adverse events (moderate certainty).

Researchers identified significant evidence gaps in the review data, leading to low certainty in many of the comparative findings, particularly regarding ICU admission, duration of hospitalization, and antiviral resistance, suggesting the need for future studies with more specific patient outcomes.

More information: Jonathan D. Baghdadi et al, The Limited Role for Antiviral Therapy in Influenza, JAMA Internal Medicine (2025). DOI: 10.1001/jamainternmed.2024.7258

Ya Gao et al, Antiviral Medications for Treatment of Nonsevere Influenza, JAMA Internal Medicine (2025). DOI: 10.1001/jamainternmed.2024.7193

Journal information:JAMA Internal Medicine

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