Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework

Abstract

IntroductionDespite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response after vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) vs BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework.MethodsThe systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were symptomatic, laboratory-confirmed SARS-CoV-2 infection, SARS-CoV-2 infection, severe SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. Evidence was evaluated using the GRADE framework.ResultsOverall, 17 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.75–0.97]; P=0.0151; I2 = 67.7%), severe SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.77–0.93]; P=0.0009; I2 = 0%), COVID-19–associated hospitalization (RR, 0.88 [95% CI, 0.79–0.97]; P<0.0001; I2 = 0%), and COVID-19–associated mortality (RR, 0.63 [95% CI, 0.44–0.90]; P=0.0119; I2 = 0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials. Based on nonrandomized studies, evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies.ConclusionThis GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.

Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany

“…The safety and efficacy of both mRNA-1273 and BNT162b2 in reducing the risk of SARS-CoV-2 infection in the general population and in adolescents have been demonstrated in numerous phase 3 clinical trials [14][15][16]. Subsequent observational studies have provided evidence of the protection offered by two doses of both mRNA vaccines against SARS-CoV-2 infection and against COVID-19 hospitalisation and hospital death [17][18][19][20][21][22], despite the emergence of variants [23][24][25], although several observational studies have demonstrated that the differences in formulation impact vaccine effectiveness [17][18][19][20][21][22].…”

Substantial reduction in the clinical and economic burden of disease following variant-adapted mRNA COVID-19 vaccines in immunocompromised patients in France

“…Although both mRNA-1273 and BNT162b2 (Pfizer-BioNTech Comirnaty) COVID-19 vaccines and their subsequent variant-adapted vaccines are based on mRNA technology, the formulations of mRNA-1273 version, including their dosages and nanoparticle mRNA delivery systems, differ [11–14]. Studies have found VE differences between previous versions of the mRNA-1273 vaccine and the corresponding BNT162b2 vaccine in both the general [15–19] and IC populations [20], with mRNA-1273 formulations resulting in greater levels of protection. Wang et al, (2023) conducted a systematic literature review and meta-analysis based on 17 studies in the IC population [20].…”

“…Studies have found VE differences between previous versions of the mRNA-1273 vaccine and the corresponding BNT162b2 vaccine in both the general [15–19] and IC populations [20], with mRNA-1273 formulations resulting in greater levels of protection. Wang et al, (2023) conducted a systematic literature review and meta-analysis based on 17 studies in the IC population [20]. The mRNA-1273 vaccine was found to be associated with a significantly lower risk of COVID-19 infection (relative risk [RR] for infection = 0.85 [95% CI 0.75-0.97]), hospitalizations (RR = 0.88 [95% CI 0.79-0.97]), and deaths (RR = 0.63 [95% CI 0.44-0.90]), compared to the BNT162b2 vaccine.…”

The potential economic impact of the updated COVID-19 mRNA fall 2023 vaccines in Japan

“…Studies on previous versions of the mRNA vaccines have found higher VE values for different versions of the Moderna mRNA-1273 vaccine compared to the Pfizer-BioNTech BNT162b2 versions, including high-risk populations. [15][16][17][18][19][20][21] Given the new Fall 2023 vaccine campaign, with updated Fall 2023 vaccines from both Moderna and Pfizer-BioNTech it is important to determine the economic and clinical consequences of vaccination during the Fall 2023, and understand the impact of newly emerging variants, to assist in the decision-making process and inform currently ongoing NIP discussions. Additionally, as the Japanese government has previously recommended and funded a Spring season vaccination campaign for select high-risk populations, the economic and clinical consequences of continuing to fund this population needs to be explored, as it likely will be a discussion subject for the NIP in 2024.…”

“…Therefore, the objective of this analysis is to estimate the economic and clinical impact of a NIP vaccination campaign from April 2024 onwards using the Fall 2023 updated mRNA COVID- 19 Moderna vaccine compared to the Fall 2023 updated mRNA COVID-19 Pfizer-BioNTech vaccine for adults 18 years of age and older, using a previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model. 22 The impact of a Spring 2024 vaccination campaign in select, high-risk individuals (60-64 high-risk and 65+ general population; 65+ general population only) is also explored.…”