mRNA-1273 vaccine reduces risk of Covid-19-related outcomes compared to BNT162b2 in U.S. veterans

1. The mRNA-1273 vaccine was shown to reduce the absolute risk of Covid-19-related outcomes in U.S. veterans compared to BNT162b2 vaccine.

2. Both mRNA-1273 and BNT162b2 vaccines were shown to reduce the absolute risk of Covid-19-related outcomes in U.S. veterans.

Evidence Rating Level: 2 (Good)     

Study Rundown: To help combat the SARS-CoV-2 (Covid-19) pandemic, messenger RNA (mRNA) vaccines have been developed and are effective against the symptomatic disease. However, the relative effectiveness between these mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), is unknown across various populations. To explore this, an observational study was performed to emulate a target trial using the database of the Department of Veterans Affairs (VA). Study patients who received either the BNT162b2 or mRNA-1273 vaccine were stratified in a 1:1 ratio according to several risk factors. The primary outcome was the incidence of Covid-19-related outcomes from symptomatic Covid-19 infection, to hospitalization caused by Covid-19, to death caused by Covid-19. Two trials were emulated, the first for the B.1.1.7 (alpha) variant and the second for the B.1.617.2 (delta) variant. The study found that both vaccines had low numbers of Covid-19-related outcomes, but the BNT162b2 group had an excess number of every type of outcome compared with mRNA-1273. Overall, this study demonstrates that while both mRNA vaccines are effective, the mRNA-1273 shows a lower risk for Covid-19-outcomes compared to the BNT162b2. This study is limited by its study design as it is not truly randomized, the potential lack of generalizability between the veteran population to the general population, and its lack of analysis on vaccine safety. This study continues to support that either vaccine is highly recommended given its strong efficacy and safety.

Click to read the study in NEJM

Relevant Reading: Comparison of SARS-CoV-2 Antibody Response by Age Among Recipients of the BNT162b2 vs the mRNA-1273 Vaccine

In-Depth [retrospective cohort]: In this retrospective, emulated target trial study, the electronic health records of 367,113 U.S. veterans were reviewed. Veterans who received a dose of a messenger RNA (mRNA) vaccine against SARS-CoV-2 between January 4 and May 14, 2021, were matched in a 1:1 ratio between those receiving the BNT162b2 or mRNA-1273, stratified for risk factors such as date of vaccine, age, sex, race, urbanicity of residence, and geographic location. Those with prior Covid-19 vaccination or infection were excluded. Time to the first incidence of Covid-19-related-outcomes was recorded including: documented SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, hospitalization due to Covid-19, intensive care unit (ICU) admission due to Covid-19, or death due to Covid-19. Two trials were run to accommodate for the timelines of the B.1.1.7 (alpha) variant and the B.1.617.2 (delta) variant. Risk curves were generated using the Kaplan-Meier estimator, and risk ratios for each outcome across a 24-week period were calculated. The study found that between each group (n=219,842), veterans receiving the mRNA-1273 experienced 4.52 events per 1000 persons (95% confidence interval, [CI], 4.17-4.84), compared to 5.75 events per 1000 persons (95%CI, 5.39-6.23) by veterans receiving BNT162b2. The BNT162b2 group also experienced a higher risk ratio across most Covid-19-outcomes compared to mRNA-1273 including documented infection (risk ratio [RR],1.27; 95%CI, 1.15-1.42), hospitalization (RR, 1.7; 95%CI, 1.42-2.24), and ICU admission (RR, 1.38; 95%CI, 1.01-2.42). Death caused by Covid-19 was an exception to this trend (RR, 1.11; 95%CI, 0.69-1.91). Taken together, these data support that mRNA-1273 is more effective at reducing Covid-19-outcomes compared to BNT162b2; however, further studies are required in more generalizable populations and to analyze safety between the two vaccines.

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