BACKGROUND: Comirnaty® received conditional marketing authorisation in December 2020 in the European Union and United Kingdom (UK). This non-interventional study is designated as a post-authorisation safety study (PASS) and is a commitment to the EMA. Objectives This PASS aims to determine whether an increased risk of 38 prespecified adverse events of special interest (AESI) exists following the administration of at least one dose of Comirnaty® in the general European population.
METHODS: Interim results from this retrospective cohort study includes Comirnaty® vaccinated and unvaccinated individuals matched 1:1 from four European countries and five electronic health record (EHR) data sources from the VAC4EU network: the Netherlands (PHARMO; general practitioner (GP) data), Italy (Pedianet; GP), Spain (EpiChron-IACS and SIDIAP; GP and inpatient), and Norway (NHR; GP and inpatient/outpatient specialist). Cumulative incidence rates of AESIs were calculated following the date of 1st dose vaccination or matched index dates in unvaccinated. Propensity score adjusted hazard ratios (HRs) were calculated within event-specific risk windows. Analyses were conducted using a common protocol, the ConcePTION common data model, and common analytical programs.
RESULTS: From vaccine launch in December 2020 until December 2022 (Pedianet, EpiChron-IACS, and SIDIAP), March 2023 (PHARMO), or December 2021 (NHR), 7,923,975 recipients of ≥1 dose of Comirnaty® were identified and matched with an unvaccinated individual (10,478 in Pedianet, 3,542,453 in NHR, 648,737 in PHARMO, 611,445 in EpiChron, and 3,110,862 in SIDIAP). No clear patterns of increased AESI risk after vaccination were identified, except for arrhythmia and hypermenorrhea in three data sources. The HRs for arrhythmia were 1.73 (95% CI: 0.79, 3.78) in Pedianet, 1.04 (95% CI: 1.00, 1.07) in NHR, 1.28 (95% CI: 1.19, 1.38) in PHARMO, 1.07 (95% CI: 0.98, 1.17) in EpiChron, and 1.02 (95% CI: 0.98, 1.06) in SIDIAP. The HRs for hypermenorrhea were 6.62 (95% CI: 0.80, 54.62) in PHARMO, 1.38 (95% CI: 1.21, 1.57) in EpiChron, and 1.09 (95% CI: 1.03, 1.16) in SIDIAP.
CONCLUSIONS: This PASS evaluated the safety of Comirnaty® through 38 prespecified AESIs, using EHR data in almost 8 million vaccinated individuals. The incidence rates of AESIs were comparable with available published background incidence rates in unvaccinated cohorts. There were small elevations in risk observed for arrhythmia in the PHARMO data source, and hypermenorrhea in the EpiChron and SIDIAP data sources. These associations are being further evaluated.
