The Moderna mRNA COVID-19 Vaccine May Be Safer in Older Adults than the Pfizer Shot, New Study Suggests

In a head-to-head safety comparison, older adults who received the COVID-19 vaccine manufactured by Moderna were slightly less likely to experience adverse events and had a 14% lower risk of diagnosed COVID-19 than those who received the Pfizer-BioNTech vaccine, according to new research published in JAMA Network Open . 

Investigators, led by Brown University scientists, examined data from more than 6 million adults with an average age >70 years, who received either the Moderna (mRNA-1273) or the Pfizer (BNT162b) shot as their first dose of COVID-19 vaccine between December 2020 and July 2021. The study population comprised solely community dwelling fee-for-service Medicare beneficiaries, a restriction that facilitated collection of relevant covariate data.

The researchers underscored the current lack of evidence specific to the older adult population regarding tolerability and efficacy of the SARS-CoV-2 immunizations noting that evidence in circulation “generalizes poorly” to this population.

They also note that no studies have yet compared the vaccines across these dimensions among subgroups with frailty or at greater risk for adverse events; moreover, older adults tend to be poorly represented in clinical trials which in the case of COVID-19 studies is unfortunate given that the elderly, and particularly those in congregate settings, are at higher risk for severe COVID-19.

To expand this evidence base, the team, led by Daniel Harris, PhD, a pharmacoepidemiologist and research scientist in the Center for Gerontology and Healthcare Research at the Brown University School of Public Health, used a retrospective cohort study design to compare the risk of potential adverse events shortly after administration of a first vaccine dose and to assess whether frailty and prior history of a predefined list of adverse events modified the comparative vaccine associations.

For their primary outcomes, Harris et al used a list of 12 serious adverse events identified by the US Food and Drug Administration that could potentially occur after mRNA vaccination (figure) and a composite of thromboembolic events. The secondary outcome of interest was 28-day risk of diagnosed COVID-19.

Investigators analyzed customer data from CVS and Walgreens linked to Medicare claims between December 2020 and July 2021. The final cohort numbered 6 388 196 adults who received the mRNA-1273 or BNT162b2 vaccine between the study dates and had 28 days of follow-up. Just more than half received BNT62b2. Average participant age was 76.3 years; 59.4% were women; and 86.5% were White. More than one-third of individuals were categorized as prefrail (38.1%) or frail (6.0%).

FINDINGS

Overall, the investigators wrote, older adults in both vaccine groups had a very low risk of adverse events, nor did the vaccines differ in risk for the majority of outcomes investigated. However, the Moderna vaccine (mRNA-1273 ) was associated with a lower risk of several of the potential events, including a 4% lower risk of pulmonary embolism and a 2% lower risk of thromboembolic events compared to the Pfizer vaccine, BNT162b2. Harris and colleagues point out that safety and efficacy are interrelated and that this finding may suggest greater protection by mRNA-1273 vs BNT162b2 against COVID-19.

The risk of being diagnosed with COVID-19 also was lower by 14% (RR 0.86; 95% CI, 0.83-0.87) among those vaccinated with mRNA-1273, a benefit the investigators found was attenuated by level of frailty (frail: RR, 0.94; 95% CI, 0.89-0.99).

“Because the risk of adverse events following natural infection exceeds that of either mRNA vaccine, vaccination with any available product should be prioritized,” the investigators wrote. “Nonetheless, mRNA-1273 was associated with a slightly lower risk of pulmonary embolism and other adverse events compared with BNT162b2. Because individuals who received mRNA-1273 also had a lower risk of diagnosed COVID-19, the reduced risk of adverse events in this vaccine group may represent the benefits of vaccination with a more effective product.

"Future research should seek to formally disentangle differences in vaccine safety and effectiveness and consider the role of frailty in assessments of COVID-19 vaccine performance.”

The study's investigators conducted the research as part of the IMPACT Collaboratory project. which allowed in-depth monitoring of the long-term safety and effectiveness of the vaccines for Medicare beneficiaries in collaboration with CVS and Walgreens.

Source: Daniel Harris et al, Comparative Risks of Potential Adverse Events Following COVID-19 mRNA Vaccination Among Older US Adults, JAMA Netw Open. 2023. Published online August 2, 2023. doi: 10.1001/jamanetworkopen.2023.26852