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Comparative Safety of BNT162b2 and mRNA-1273 Vaccines in a Nationwide Cohort of US Veterans

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  How do risks of adverse events compare after vaccination with BNT162b2 (Pfizer-BioNTech) vs mRNA-1273 (Moderna Inc) vaccines?

Findings  In this cohort study of 433 672 US veterans during 38 weeks of follow-up, recipients of the BNT162b2 vaccine, compared with recipients of the mRNA-1273 vaccine, had an excess per 10 000 persons of 10.9 ischemic stroke events, 14.8 myocardial infarction events, 11.3 other thromboembolic events, and 17.1 kidney injury events. Small-magnitude differences between the 2 vaccines were seen within 42 days of the first dose, and few differences were seen within 14 days of the first dose.

Meaning  This study’s findings suggest that there were few differences in risk of adverse events within 14 days of the first dose of either the BNT162b2 or the mRNA-1273 vaccine and small-magnitude differences within 42 days and 38 weeks of the first dose.

Abstract

Importance  The risk of adverse events has been found to be low for participants receiving the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna Inc) vaccines in randomized trials. However, a head-to-head comparison of their safety for a broader range of potential adverse events over longer follow-up and in larger and more diverse populations is lacking, to our knowledge.

Objective  To compare the head-to-head safety in terms of risk of adverse events of the BNT162b2 and mRNA-1273 vaccines in the national health care databases of the US Department of Veterans Affairs, the largest integrated health care system in the US.

Design, Setting, and Participants  In this cohort study, the electronic health records of US veterans who received a first dose of the BNT162b2 or mRNA-1273 vaccine between January 4 and September 20, 2021, were used. Recipients of each vaccine were matched in a 1:1 ratio according to their risk factors.

Exposures  Vaccination with either the BNT162b2 vaccine, with a second dose scheduled 21 days later, or the mRNA-1273 vaccine, with a second dose scheduled 28 days later.

Main Outcomes and Measures  A large panel of potential adverse events was evaluated; the panel included neurologic events, hematologic events, hemorrhagic stroke, ischemic stroke, myocardial infarction, other thromboembolic events, myocarditis or pericarditis, arrhythmia, kidney injury, appendicitis, autoimmune events, herpes zoster or simplex, arthritis or arthropathy, and pneumonia. Risks over 38 weeks were estimated using the Kaplan-Meier estimator.

Results  Among 433 672 persons included in the matched vaccine groups, the median age was 69 years (IQR, 60-74 years), 93% of individuals were male, and 20% were Black. Estimated 38-week risks of adverse events were generally low after administration of either the BNT162b2 or the mRNA-1273 vaccine. Compared with the mRNA-1273 group, the BNT162b2 group had an excess per 10 000 persons of 10.9 events (95% CI, 1.9-17.4 events) of ischemic stroke, 14.8 events (95% CI, 7.9-21.8 events) of myocardial infarction, 11.3 events (95% CI, 3.4-17.7 events) of other thromboembolic events, and 17.1 events (95% CI, 8.8-30.2 events) of kidney injury. Estimates were largely similar among subgroups defined by age (<40, 40-69, and ≥70 years) and race (Black, White), but there were higher magnitudes of risk differences of ischemic stroke among older persons and White persons, kidney injury among older persons, and other thromboembolic events among Black persons. Small-magnitude differences between the 2 vaccines were seen within 42 days of the first dose, and few differences were seen within 14 days of the first dose.

Conclusions and Relevance  The findings of this cohort study suggest that there were few differences in risk of adverse events within 14 days of the first dose of either the BNT162b2 or the mRNA-1273 vaccine and small-magnitude differences within 42 days of the first dose. The 38-week risks of adverse events were low in both vaccine groups, although risks were lower for recipients of the mRNA-1273 vaccine than for recipients of the BNT162b2 vaccine. Although the primary analysis was designed to detect safety events unrelated to SARS-CoV-2 infection, the possibility that these differences may partially be explained by a lower effectiveness of the BNT162b2 vaccine in preventing the sequelae of SARS-CoV-2 infection compared with the mRNA-1273 vaccine could not be ruled out. These findings may help inform decision-making in future vaccination campaigns.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: April 21, 2022.

Published Online: June 13, 2022. doi:10.1001/jamainternmed.2022.2109

Corresponding Author: Arin L. Madenci, MD, PhD, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115 (arin_madenci@g.harvard.edu).

Author Contributions: Drs Dickerman and Madenci contributed equally to this work, had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Dickerman, Madenci, Gagnon, Cho, Casas, Hernán.

Acquisition, analysis, or interpretation of data: Dickerman, Madenci, Gerlovin, Kurgansky, Wise, Figueroa Muñiz, Ferolito, Gagnon, Gaziano, Cho, Hernán.

Drafting of the manuscript: Dickerman, Madenci, Cho, Casas, Hernán.

Critical revision of the manuscript for important intellectual content: Dickerman, Madenci, Gerlovin, Kurgansky, Wise, Figueroa Muñiz, Ferolito, Gagnon, Gaziano, Cho, Hernán.

Statistical analysis: Dickerman, Madenci, Gagnon, Hernán.

Obtained funding: Gaziano, Cho, Casas, Hernán.

Administrative, technical, or material support: Gaziano, Cho.

Supervision: Gaziano, Cho, Hernán.

Conflict of Interest Disclosures: Mr Ferolito reported completing a 6-month paid internship with Moderna Therapeutics to help develop bioinformatic next-generation sequencing pipelines and owning 5 shares of Moderna Therapeutics stock purchased in February 2020 outside the submitted work. Dr Hernán reported receiving grants from the US Department of Veterans Affairs (VA) during the conduct of the study and personal fees from Cytel and ProPublica outside the submitted work. No other disclosures were reported.

Funding/Support: This research was supported in part by the VA Office of Research and Development Cooperative Studies Program (CSP) Epidemiology Center at the VA Boston Healthcare System through CSP 2032, by resources and the use of facilities at the VA Boston Healthcare System and VA Informatics and Computing Infrastructure (VINCI) (VA HSR RES 13-457), and by the use of data from the VA COVID-19 Shared Data Resource. Dr Dickerman is supported by grant K99 CA248335 from the National Institutes of Health. Dr Gerlovin and Mr Ferolito are supported by grant MVP000 from the VA Million Veteran Program. Mr Figueroa Muñiz is supported by grant T32 GM140972 from the National Institute of General Medical Sciences Interdisciplinary Training Program for Biostatisticians.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The contents of this article do not represent the views of the VA or the US government. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of Health and Human Services and its agencies, including Biomedical Advanced Research and Development Authority and the Food and Drug Administration, as well as any other agency of the US government. Assumptions made within and interpretations from the analysis do not necessarily reflect the position of any US government entity.

Additional Contributions: We thank Daniel C. Posner, PhD, and Yuk-Lam (Anne) Ho, MPH (both Massachusetts Veterans Epidemiology Research and Information Center [MAVERIC]), for insights on COVID-19 data extraction and phenotype definitions and Constance A. Hoag, BA (MAVERIC), for management of the administrative and regulatory aspects of the project. We also thank the VA COVID-19 Shared Data Resource team for their contributions and support and the VA health care providers, employees, and volunteers for their dedication to caring for our veterans throughout this pandemic. These individuals were not paid for their contributions.

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