Safety monitoring of health outcomes following influenza vaccination during the 2023-2024 season among US Medicare beneficiaries aged 65 years and older

Background: Influenza vaccination is widely recommended for individuals aged 6 months and older in the United States. While the safety of annual influenza vaccines is well established, FDA conducts routine monitoring and safety evaluations. This study assessed the safety of 2023-2024 influenza vaccines among elderly Medicare beneficiaries. Methods: A self-controlled case series (SCCS) analysis compared incidence rate ratios (IRR) of anaphylaxis, encephalitis/encephalomyelitis/acute disseminated encephalomyelitis, Guillain-Barre<acute accent> syndrome (GBS), transverse myelitis, hemorrhagic stroke, non-hemorrhagic stroke, transient ischemic attack (TIA), and non-hemorrhagic stroke/TIA, following 2023-2024 seasonal influenza vaccinations in risk and control intervals among Medicare beneficiaries aged 65 years and older. We used conditional Poisson regression to estimate IRRs and 95 % confidence intervals (CIs) adjusted for event-dependent observation time for certain outcomes, seasonality, and uncertainty from outcome misclassification where feasible. For health outcomes with statistically significant associations, we stratified results by concomitant vaccination status. Results: We observed 20,258,006 influenza vaccinees, and no statistically significant elevations of risk for anaphylaxis, encephalitis/encephalomyelitis (with ADEM), GBS, hemorrhagic stroke, or transverse myelitis. For the combined non-hemorrhagic stroke/TIA outcome (22-42-day risk window), we observed a small elevation in risk that was statistically significant in both the Fee-for-Service (IRR: 1.07; 95 % CI: 1.01, 1.14) and Medicare Advantage (IRR: 1.10; 95 % CI: 1.02, 1.17) populations that received a high-dose vaccine. This was also observed among Medicare Advantage beneficiaries that received any influenza vaccine (IRR: 1.11; 95 % CI: 1.01, 1.22). Additionally, we observed a small statistically significant risk for the individual TIA outcome (22-42-day risk window) among the Medicare Advantage population that received any influenza vaccine. Conclusion: The benefits of seasonal influenza vaccines established by past studies likely outweigh the risks found in this study. The small, elevated risk of stroke outcomes must be carefully considered in light of the known benefits of influenza vaccination.