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

Katherine E Mues, Brenna Kirk, Deesha A Patel, Alice Gelman, L Scott Chavers, Carla A Talarico, Daina B Esposito, David Martin, James Mansi, Xing Chen, Nicolle M Gatto, Nicolas Van de Velde, Katherine E Mues, Brenna Kirk, Deesha A Patel, Alice Gelman, L Scott Chavers, Carla A Talarico, Daina B Esposito, David Martin, James Mansi, Xing Chen, Nicolle M Gatto, Nicolas Van de Velde

Abstract

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.

Keywords: COVID-19; Immunocompromised; SARS-CoV-2; Vaccine effectiveness; mRNA-1273.

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LSC, DBE, DM, JM, CV, XC, and NV are employees of Moderna, Inc. and hold stock/stock options in the company. CAT was an employee of and a shareholder in Moderna, Inc. at the time of these analyses; CAT is currently an employee of AstraZeneca. KEM, BK, DAP, AG, and NMG are employees of Aetion, Inc., which has been contracted by Moderna, Inc., for the conduct of the present study. KEM is a stock option holder of Aetion, Inc. NMG is a stock option holder of Aetion, Inc and owns stock in Pfizer, Inc. .

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Study design schema. Immunocompromised adults who had completed a 2-dose homologous vaccine regimen were identified via central procedural terminology (CPT) and nation drug codes (NDC) from December 11, 2020, through January 10, 2022.
Fig. 2
Fig. 2
Participant attrition diagram. Participant attrition flow diagram using claims from the HealthVerity database. Numbers represent the patient size before inverse probability of treatment weighting.
Fig. 3
Fig. 3
Comparative VE over time. Kaplan–Meier plots with 95% confidence intervals and Schoenfeld residuals over time. A) Medically-attended COVID-19; B) COVID-19 hospitalization.
Fig. 4
Fig. 4
Sensitivity analyses for medically-attended COVID-19. Forest plot of hazard ratios of mRNA-1273 versus BNT-1626b in primary and sensitivity analyses of medically-attended COVID-19 data.
Fig. 5
Fig. 5
Sensitivity analyses for COVID-19 hospitalization. Forest plot of hazard ratios of mRNA-1273 versus BNT-1626b in primary and sensitivity analyses of COVID-19 hospitalization data.

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Source: PubMed

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