Safety Monitoring of Multiple Health Outcomes Following 2023-2024 COVID-19 Vaccination among Medicare Beneficiaries Aged 65 Years and Older in the United States

BackgroundCOVID-19 vaccines are well-established as safe. However, continued surveillance of COVID-19 vaccines is important to ensure the safety of newly formulated vaccines. This study evaluated the association between vaccination with 2023-2024 formula COVID-19 vaccines and multiple health outcomes among Medicare beneficiaries aged 65 years and older in the United States. MethodsThe study used health plan data from the Medicare Fee-for-Service (FFS) claims database and extended from September 2023 to April 2024. We monitored the uptake of 2023-2024 COVID-19 vaccines (Pfizer-BioNTech, Moderna, Novavax), and where case counts were available, we used a self-controlled case series design to assess the association between vaccination and prespecified health outcomes. We used conditional Poisson regression to estimate incidence rate ratios (IRRs), attributable risks (ARs) and corresponding 99% confidence intervals (CIs). Analyses were adjusted for outcome seasonality, event-dependent observation time for outcomes with high case fatality rates, and outcome misclassification where feasible. ResultsApproximately 7.6 million Medicare FFS beneficiaries received a 2023-2024 COVID-19 vaccination. There was an even distribution of people who received Pfizer-BioNTech (3,689,356; 48.80%) or Moderna (3,841,245; 50.80%) vaccinations and very few who received Novavax (30,171; 0.40%). There was a statistically significant elevation in anaphylaxis risk associated with 2023-2024 Pfizer-BioNTech vaccines in the seasonality-adjusted analysis (IRR: [99% CI: 1.07, 15.30]) that was no longer statistically significant after accounting for potential outcome misclassification (IRR: 3.90 [99% CI: 0.49, 30.90]). Anaphylaxis cases attributable to 2023-2024 Pfizer-BioNTech vaccination were rare (AR per 100,000 doses: 0.09 [99% CI: -0.08, 0.25]). No other statistically significant elevations in risk were observed. ConclusionThere were no new safety signals identified following 2023-2024 COVID-19 vaccinations among U.S. Medicare beneficiaries aged 65 years and older. A potential, but rare, elevation in anaphylaxis incidence rates following 2023-2024 Pfizer-BioNTech COVID-19 vaccination was observed. HIGHLIGHTSO_LIWe studied 7,560,772 Medicare enrollees [≥]65 years old who received 2023-2024 COVID-19 vaccines C_LIO_LINo new safety signals were identified in the Medicare population [≥]65 years old C_LIO_LIA potential-but rare-elevation in anaphylaxis risk was associated with vaccination C_LIO_LINo increased risk of any other prespecified health outcomes was found C_LI