Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework

Abstract

BackgroundThe mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against SARS-CoV-2 infection in phase 3 clinical trials, including among older adults. To inform COVID-19 vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults.MethodsWe systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022 and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19‒related hospitalization, and COVID-19‒related death following ≥2 vaccine doses. Random-effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-squared testing. Evidence certainty was assessed per GRADE framework.Results24 non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), COVID-19‒related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) and COVID-19‒related death (RR 0.80 [95% CI 0.64‒0.99]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I2>75%) except death (I2=0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized-controlled trial data.ConclusionMeta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections; hospitalizations; and deaths with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥50 years.SUMMARY POINTSThe COVID-19 pandemic has disproportionately affected older adults, as this population is generally more susceptible to infection and severe outcomes due to immune senescence and underlying comorbidities.The 2 available mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against SARS-CoV-2 infection in phase 3 clinical trials, including among older adults.To inform COVID-19 vaccine selection, this systematic literature review and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 among older adults in real-world settings.Vaccination with homologous primary or booster mRNA-1273 was associated with significantly lower risk of infection (including asymptomatic, symptomatic, and severe infections), hospitalization, and death due to COVID-19 than vaccination with BNT162b2 in older adults aged ≥50 years.