(A-260) Safety of Moderna’s Omicron-Containing Bivalent and XBB1.5- containing Monovalent Vaccines: Results from a US Claims Database Cohort Study

Background: Moderna conducted active surveillance in administrative claims to evaluate adverse events of special interest (AESI) defined by the Brighton Collaboration following Spikevax bivalent (mRNA-1273.222) or monovalent (mRNA-1273.815) vaccination (referred to as Spikevax).

Objectives: To assess the risk of myocarditis, pericarditis and 39 other AESI following Spikevax vaccination to supplement routine safety surveillance.

Methods: This retrospective observational study used US healthcare claims data (HealthVerity) in adults ≥18 years to assess the risk of AESI following ≥1 dose of Spikevax between 9/1/2022 - 1/15/2024. In the first cohort, Spikevax recipients without concurrent influenza vaccination were compared to influenza vaccine recipients. Separately, a second cohort of Spikevax recipients with or without influenza vaccination were compared to individuals with medically-attended COVID-19.

Propensity score weighting estimated the probability of receiving Spikevax conditional on baseline demographics and comorbidities. The incidence rate (IR) of each AESI was estimated, and Cox proportional hazards (PH) regression assessed the relationship between Spikevax vs. influenza vaccination and each AESI. Restricted mean survival time (RMST) was used for Cox models not meeting the PH assumption. AESI with suggested increased risks were further assessed via self-controlled risk interval (SCRI) analyses. Comparisons to individuals with medically-attended COVID-19 were limited to weighted IR to descriptively assess risk of each AESI following infection compared to vaccination. Subgroup analyses (e.g., by age and sex) were conducted.

Results: Among 1,146,808 Spikevax and 13,082,338 influenza vaccinations, six and 33 cases of myocarditis were observed, respectively. The PH assumption was not met estimating the risk of myocarditis in the 1-7 day risk window, and RMST suggested no increased risk post vaccination (RMST ratio = 0.999999, 95% CI: 0.999997 - 1.000001). Two and 80 cases of pericarditis were observed following Spikevax and influenza vaccination, respectively, with no increased risk (weighted hazard ratio = 0.35, 95% CI: 0.08-1.55). SCRI analyses found no increased myocarditis or pericarditis risk within 1-7 days post-vaccination. No other AESI met the threshold for SCRI analyses.

Among 3,059,540 Spikevax vaccinations and 2,573,696 episodes of medically-attended COVID-19, the IR of myocarditis, pericarditis, and almost all other AESI was higher following medically-attended COVID-19 than after Spikevax.

Conclusions: This analysis supports the known safety profile of Spikevax, with no new safety signals identified. The IR of AESI were similar or lower following Spikevax than after medically-attended COVID-19.