(081) Active surveillance and evaluation of anosmia/ageusia following mRNA-1273 administration: Learnings from a US administrative claims database study

Publication Number: 1076

Background: Moderna, Inc. is conducting active surveillance in an administrative claims database to evaluate potential risks of adverse events of special interest (AESI) after mRNA-1273 vaccine administration, including anosmia/ageusia, a loss of smell and taste. Challenges arise when considering a potential safety outcome that is a symptom of COVID-19.

Objectives: To illustrate challenges in estimating the risk of anosmia/ageusia following mRNA-1273 vaccination among US adults using administrative claims data.

Methods: In an ongoing surveillance study of pre-specified AESI using medical and pharmacy claims data from HealthVerity, incidence rates (IR) following mRNA-1273 vaccination were estimated per 100,000 person-years (PY) and compared to background rates from 2 historical time periods (pre-COVID and COVID era prior to authorization of vaccines). Where signal criteria were met, self-controlled risk interval (SCRI) analyses were conducted. For anosmia/ageusia, SCRI event rate ratios (ERR) and 95% CI comparing rates in a 28-day risk window after vaccination to a 42-day control window were calculated. In primary analyses, patients were censored on a COVID-19 diagnosis. A sensitivity analysis was implemented without censoring on COVID-19. All analyses were stratified by age, gender, dose, heterologous vaccination, and immunocompromised status.

Results: The incidence of anosmia/ageusia was 49.04 cases per 100,000 person-years (95% CI 48.12-49.97) in the pre-COVID-19 era and 151.26 (95%CI 149.55-152.97) in the COVID-19 era prior to authorization of vaccines. Among 23,614,853 adult mRNA-1273 vaccinees through 31 Jul 22, 18,721 (0.08%) had an anosmia event following vaccination (IR 134.48, 95% CI 132.55-136.41). Comparison of post-vaccination incidence vs the pre-COVID rate met criteria for additional evaluation. Primary dose-agnostic SCRI analysis showed an ERR of 1.09 (95% CI 1.04–1.15) which ranged from 0.56 (0.29–1.10) to 2.53 (0.74–8.65) across subgroup analyses considered. Without censoring on COVID-19, the dose-agnostic SCRI analysis included 818 additional cases and ERRs of greater magnitude with an overall 19.9% increase in risk window events (n = 4,036) and a 5.0% increase in control period events (n = 3,066, ERR 1.31, 95% CI 1.25-1.38).

Conclusions: Self-controlled analyses to evaluate the risk of anosmia/ageusia following administration of COVID-19 vaccines such as mRNA-1273 may be impacted occurrence of COVID-19 infection, which is more likely to occur during the post-vaccination risk window when vaccines have not yet taken effect. When evaluating potential safety signals of AESI known to be associated with the target indication, appropriate censoring criteria should be considered.