A large retrospective cohort analysis of over 75,000 U.S. electronic health records found that baloxavir (Xofluza) was more effective than oseltamivir (Tamiflu) in reducing influenza-related hospitalizations and emergency department visits. Published in the International Journal of Infectious Diseases, the study provides important real-world evidence supporting baloxavir’s superior effectiveness in routine clinical practice. The study was conducted by Chien-Hsien and colleagues.
The current retrospective observational study analyzed data from the TriNetX US Collaborative Network, which includes 69 healthcare organizations. Patients diagnosed with influenza between January 1, 2016, and December 31, 2023, were included. The study compared 73,899 patients treated with oseltamivir to 1,592 patients treated with baloxavir. To minimize confounding factors, 1:1 propensity score matching (PSM) was performed to make sure that baseline characteristics were balanced between the two groups. The patients were divided into two groups, according to antiviral therapy: oseltamivir versus baloxavir. Main outcomes included all-cause hospitalization, ED visits, and all-cause mortality at 1, 3, and 6 months after the index treatment.
Key Findings
Hospitalization rates:
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1-month: oseltamivir 1.6% vs baloxavir 0.6%
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3-month: 3.7% vs 0.6%
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6-month: 5.3% vs 0.8% (HR 6.49; 95% CI, 3.55–11.90)
Emergency department visits:
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1-month: oseltamivir 1.8% vs baloxavir 1.5%
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3-month: 4.4% vs 3.5%
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6-month: 7.2% vs 5.0% (HR 1.34; 95% CI, 1.01–1.78)
All-cause mortality: 0.6% for both groups (HR 0.96; 95% CI, 0.14–6.78), showing no significant difference.
In this large real-world analysis, influenza outpatients treated with baloxavir had significantly lower rates of hospitalizations and ED visits compared to those treated with oseltamivir, whereas mortality rates were similar. These findings support the use of baloxavir as an effective outpatient antiviral therapy that may reduce healthcare utilization without compromising survival.
Reference:
Huang, C. H., Chen, M. T., & Tsai, M. H. (2025). Comparison of clinical outcomes of oseltamivir versus baloxavir in outpatients with influenza: a retrospective cohort analysis. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 108277. Advance online publication. https://doi.org/10.1016/j.ijid.2025.108277