(A-329) Safety Monitoring of Health Outcomes following Influenza Vaccination during the 2023–2024 Season among U.S. individuals aged 6 months through 64 years

Background: Influenza vaccination is widely recommended for individuals aged 6 months and older in the United States. Although the safety of annual influenza vaccines is well established, FDA conducts routine monitoring of the reformulated vaccines to evaluate their safety. This study assessed the safety of 2023–2024 influenza vaccines among vaccinees aged 6 months through 64 years.

Objectives: To evaluate the risk of select health outcomes following vaccination with the 2023–2024 seasonal influenza vaccines among individuals aged 6 months through 64 years.

Methods: In this self-controlled case series study of 2023–2024 influenza vaccine recipients aged 6 months – 64 years, the incidence rates of select health outcomes were compared during pre-specified risk and control intervals following vaccination. Nine health outcomes were monitored; anaphylaxis, encephalitis/encephalomyelitis with acute disseminated encephalomyelitis (ADEM), Guillain-Barré syndrome (GBS), transverse myelitis (TM), hemorrhagic stroke (HS), non-hemorrhagic stroke (NHS), transient ischemic attack (TIA), and NHS or TIA in all ages; and febrile seizure in children aged 6 months – 5 years. Data from three commercial data partners (CVS Health, Carelon Research, Optum) were included during the study period, August 1, 2023 through August 31, 2024. Influenza vaccines were classified as any quadrivalent, or Standard Dose-IIV4 (SD-IIV4) influenza vaccine. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) adjusted for event-dependent observation time for select outcomes and seasonality. A meta-analysis was performed to pool results from all three databases for higher precision and statistical power using both random- and fixed-effects models.

Results: Following 1.9 million (Optum), 2.5 million (CVS), and 3.7 million (Carelon Research) 2023–2024 influenza dose administrations, no statistically significant elevations of risk were observed for anaphylaxis, encephalitis/encephalomyelitis (with ADEM), GBS, HS, NHS, combined NHS/TIA, or TM. Small yet statistically significant elevations in risk were observed in both fixed and random-effect seasonality-adjusted meta-analyses for TIA in all ages (IRR: 1.29 [95% CI: 1.05, 1.59]) and febrile seizures among children 6 months – 5 years (IRR: 1.67 [95% CI: 1.16, 2.41]) after any influenza vaccine.

Conclusions: Results from this study indicate that the risks of seasonal influenza vaccines appear to be minimal. The small statistically significant increased risk of TIA and febrile seizures observed in the study may need to be carefully considered on an individual basis in light of the known benefits of influenza vaccination, with further research focusing on these outcomes.