Weibel D, de Luise C, De Jong H, Cid Royo A, Ryan O, Manders E, Choi J, Mildiner Moraga S, Mohammadi S, Dehghan Tarazjani A, Hoxhaj V, Riera-Arnau J, Aguado J, Marsal J, Garcia de Albeniz X, Weinrib R, Pazos I, Pala E, Haugh M, Poblador-Plou B, Gimeno-Miguel A, Santos-Mejias A, Marconi E, Barbieri E, Stona L, Gaspersz J, Overbeek J, Roy D, Lane S, Fry C, Morris D, Hyeraci G, Lupattelli A, Desalegn A, Martinez FV, Bissacco CA, Rubino H, Sturkenboom M, Arana A. Results from the vaccine monitoring collaboration for Europe (VAC4EU) post-authorisation safety study for the Pfizer-BioNTech COVID-19 vaccine (Comirnaty®) in Europe. Presented at the ISPE 42nd Annual Meeting; September 1, 2026. Milan, Italy.

BACKGROUND: Comirnaty® received conditional marketing authorisation in the EU, UK and US in December 2020. We describe results from a post-authorisation safety study; a commitment to the EMA and postmarketing requirement to the FDA.

OBJECTIVES: Determine the risk of 37 adverse events of special interest (AESIs) and 11 pregnancy related and neonatal AESIs following ≥1 dose of Comirnaty in the general European population.

METHODS: This VAC4EU study follows a retrospective cohort design using data from 6 European electronic health record data sources in 5 countries: Italy (Pedianet, general practitioner (GP)); Netherlands (PHARMO Data Network, GP); Norway (NHR, inpatient and outpatient); Spain (EpiChron, GP and inpatient, SIDIAP, GP and inpatient/outpatient specialist); and United Kingdom (CPRD Aurum, GP). Comirnaty-vaccinated were matched 1:1 with unvaccinated on age, sex and other demographic and clinical factors. Propensity score-adjusted hazard ratios (HRs) were estimated for event-specific risk windows. Analyses were conducted using a common protocol (EUPAS41623), the ConcePTION common data model and common analytical programs.

RESULTS: From December 2020 to June 2023 (CPRD Aurum), December 2022 (Pedianet, NHR), June 2023 (PHARMO, SIDIAP) and July 2023 (EpiChron), 11,496,929 recipients of ≥1 dose of Comirnaty were matched. All estimates are expressed as pooled HR (95% CI). Prior AESIs in risk management plans were myocarditis (1.32; 0.74–2.34) and anaphylaxis (2.52; 0.27–23.28). AESIs identified as signals and discussed by PRAC were idiopathic thrombocytopenia (0.77; 0.50–1.17), thrombosis with thrombocytopenia syndrome (1.24; 0.44–3.46), myositis (1.05; 0.86–1.29), erythema multiforme (0.87; 0.35–2.14), glomerulonephritis (0.92; 0.62–1.38), hypermenorrhoea (1.24; 1.02–1.51), secondary amenorrhoea (1.14;0.90–1.44), and multisystem inflammatory syndrome (1.11; 0.42–2.96). Other events reported in the literature included acute cardiovascular injury (1.22; 1.04–1.42), arrhythmia (1.22; 1.05–1.42), heart failure(1.01; 0.73–1.38), stress cardiomyopathy (1.23; 0.77–1.96), coronary artery disease (1.14; 0.87–1.50), coagulation disorders (0.85; 0.76–0.95), cerebral venous sinus thrombosis (0.74; 0.06–8.83), single organ cutaneous vasculitis (0.82; 0.03–2.25), and subacute thyroiditis (1.89; 1.20–2.96).

CONCLUSIONS: There was no increased risk for most AESIs. Confidence intervals for hypermenorrhoea, acute cardiovascular injury, arrhythmia and subacute thyroiditis were compatible with harmful effects. Effect estimates on myocarditis and anaphylaxis were concordant with prior studies.