(342) Final Results from Post-Emergency Use Authorization (EUA) Active Safety Surveillance Study among Individuals in the Veterans Affairs Health System Receiving Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) Vaccine

Background: On 01/29/2021, Pfizer, in collaboration with the US Veterans Health Administration (VHA) and Analysis Group, initiated an EUA active surveillance study (C4591012) among VHA enrollees.

Objectives: To assess whether the VHA population experience increased risk of safety events of interest after receiving Pfizer-BioNTech COVID-19 vaccine.

Methods: Electronic medical record data from US VHA were used to conduct rapid-cycle, longitudinal, cohort study analyses. The study period began on 12/11/2020 (US FDA EUA approval date) and data collection concluded on 06/30/2023. In this final analysis, different methods of analyses for signal detection and evaluation were conducted for 48 pre-specified safety events of interest and a prioritized analysis of myocarditis/pericarditis following Pfizer-BioNTech COVID-19 vaccine monovalent doses 1-4 and bivalent dose 1.

Results: A total of 1,652,514 VHA enrollees with mean age of 64.0 years received ≥ 1 dose of the Pfizer-BioNTech COVID-19 vaccine.

Using self-controlled risk interval design and active comparator design with historical seasonal influenza vaccinees, cerebrovascular non-hemorrhagic stroke, other acute demyelinating disease, acute myocardial infarction, anaphylaxis, arrhythmia, coronary artery disease, myocarditis, chilblain-like lesions, pulmonary embolism, optic neuritis, heart failure and cardiogenic shock, acute kidney injury, stress cardiomyopathy, deep vein thrombosis, Guillain-Barré Syndrome, microangiopathy, hemorrhagic disease, and severe COVID-19 disease were initially detected as potential signals. No signal remained after signal evaluation analyses including multivariate Poisson regression and self-controlled case series design with pre-specified signal definition of effect estimate >3 and p-value < 0.01. Results were generally consistent among the subgroup enrolled in the VHA with dual Medicare coverage.

For myocarditis/pericarditis, there were 52 cases within the 21-day risk interval after any dose of the Pfizer-BioNTech COVID-19 vaccine, and rates were not significantly different between the risk vs. comparison interval among vaccinees for aggregated doses (adjusted incidence rate ratio [95% CI]: 0.96 [0.66, 1.40]). Of the 52 cases, 36 were confirmed through chart review, which included 34 (94.4%) individuals with pericarditis, 6 (16.7%) with myocarditis. The majority of cases recovered by the end of follow-up (mean of 6.0 months).

Conclusions: None of the safety events of interest were found to be associated with Pfizer-BioNTech COVID-19 vaccine based on the signal detection and evaluation analyses. No signals were detected for myocarditis/pericarditis, although the small sample size of young men in the VHA population provided limited statistical power.