Real-world comparative effectiveness of mRNA-1273 and BNT162b2 vaccines among immunocompromised adults identified in administrative claims data in the United States

INTRODUCTION: Head-to-head studies comparing COVID-19 mRNA vaccine effectiveness in immunocompromised individuals, who are vulnerable to severe disease are lacking, as large sample sizes are required to make meaningful inferences. METHODS: This observational comparative effectiveness study was conducted in closed administrative claims data from the US HealthVerity database (December 11, 2020-January 10, 2022, before omicron). A 2-dose mRNA-1273 versus BNT162b2 regimen was assessed for preventing medically-attended breakthrough COVID-19 diagnosis and hospitalizations among immunocompromised adults. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) using weighted Cox proportional hazards models were calculated. RESULTS: Overall, 57,898 and 66,981 individuals received a 2-dose regimen of mRNA-1273 or BNT161b2, respectively. Among the weighted population, mean age was 51 years, 53 % were female, and baseline immunodeficiencies included prior blood transplant (8%–9%), prior organ transplant (7%), active cancer (12%–13%), primary immunodeficiency (5–6%), HIV (20%–21%), and immunosuppressive therapy use (60%–61%). Rates per 1,000 person-years (PYs; 95% confidence intervals [CI]s) of breakthrough medically-attended COVID-19 were 25.82 (23.83–27.97) with mRNA-1273 and 30.98 (28.93, 33.18) with BNT162b2 (HR, 0.83; 95% CI, 0.75–0.93). When requiring evidence of an antigen or polymerase chain reaction test before COVID-19 diagnosis, the HR for medically-attended COVID-19 was 0.78 (0.67–0.92). Breakthrough COVID-19 hospitalization rates per 1,000 PYs (95% CI) were 3.66 (2.96–4.51) for mRNA-1273 and 4.68 (3.91–5.59) for BNT162b2 (HR, 0.78; 0.59–1.03). Utilizing open and closed claims for outcome capture only, or both cohort entry/outcome capture, produced HRs (95% CIs) for COVID-19 hospitalization of 0.72 (0.57–0.92) and 0.66 (0.58–0.76), respectively. CONCLUSIONS: Among immunocompromised adults, a 2-dose mRNA-1273 regimen was more effective in preventing medically-attended COVID-19 in any setting (inpatient and outpatient) than 2-dose BNT162b2. Results were similar for COVID-19 hospitalization, although statistical power was limited when using closed claims only. STUDY REGISTRATION: NCT05366322.