(332) Associations Between the Latest Received Dose of mRNA COVID-19 Vaccine Product and Chronic or Other Types of Urticaria: Nationwide Registry-Based Cohort Study in Denmark

Background: The Danish Medicines Agency, as a regulatory authority, is committed to monitoring the safety of COVID-19 vaccines. The present study was conducted following a safety signal suggesting a potential association between mRNA COVID-19 vaccine products (Comirnaty, Pfizer–BioNTech [BNT]; Spikevax, Moderna [MOD]) and urticaria.

Objectives: To compute the indirectly standardized incidence ratios (SIR) separately for chronic and other types of urticaria following the last administered mRNA COVID-19 vaccine product dose using the pre-pandemic general population as a comparator cohort.

Methods: This was a registry-based cohort study. The vaccinated cohort comprised all Danish residents aged 5+ years who received at least one dose of the mRNA COVID-19 vaccine product and whose latest vaccination was in December 2020-July 2023. Exclusion criteria were any vaccination with an adenoviral vector vaccine and preexisting chronic or other types of urticaria. The cohort was followed until the earliest of the outcome, COVID-19 infection, the end of the outcome risk window at 90 or 180 days since the latest vaccination date, death, emigration, or data end in October 2023.
The pre-pandemic general population aged 5+ years (2017-19) was the comparator cohort.
We computed SIR with the corresponding 95% CIs overall and across vaccine sequence-, sex-, and age-specific strata.

Results: There were 4,700,301 vaccinated; the median age was 48 years; 50% were women. Of vaccinated, 87%, 10%, and 3% adhered to BNT, MOD, and BNT-MOD mRNA COVID-19 vaccine sequence, respectively. There were 5,480,146 individuals in the comparator cohort; median age was 41 years; 50% were women.
Following all vaccine product sequences for 90 days, SIR (95% CI) for chronic urticaria was 0.83 (0.71-0.96). For BNT-MOD and BNT vaccines sequence adherers, SIRs (95% CIs) were 0.46 (0.12-1.20) and 0.61 (0.50-0.73), respectively. In MOD vaccine sequence adherers, there were 55 observed vs 18 expected events (SIR, 95% CI: 3.00, 2.27-3.88); similar results remained for the 180-day follow-up (2.86, 2.31-3.48). The subgroup analyses showed higher SIR for men vs women and for the age category 18-39 vs 40+ years.
Following all vaccine product sequences for 90 days, SIR (95% CI) for other types of urticaria was 1.14 (1.03-1.25). For BNT-MOD and BNT vaccine sequence adherers, SIRs were below or close to the null value. In the MOD vaccine sequence adherers, there were 130 observed vs 36 expected events (SIR, 95% CI: 3.65, 3.06-4.31); SIR>1 persisted in strata-specific analyses.

Conclusions: Following the most recent dose, there were larger than expected numbers of chronic and other types of urticaria in MOD but not BNT or BNT-MOD mRNA COVID-19 vaccination sequence adherers; however, the observed numbers of events were low.