Analysis of vaccine adverse events associated with rheumatoid arthritis: A pharmacovigilance study based on the VAERS database

Abstract

ABSTRACT Vaccination is a principal method of infectious disease prevention, but its association with rheumatoid arthritis (RA) remains controversial. This study assessed vaccine‑associated RA using the Vaccine Adverse Event Reporting System (VAERS). Data from 1990 to 2026 were extracted. Descriptive statistics, Weibull fitting, and disproportionality analysis using four methods, including the reporting odds ratio (ROR), along with subgroup analyses by age, sex, and pre‑/post‑COVID, were performed. Among 11,532,185 reports, 34,498 RA‑related adverse events (AEs) (0.03%) involved 5006 subjects. Females comprised 77.9% and 18–65 predominated. Serious outcomes occurred in 13.48%. Most AEs (47.49%) were musculoskeletal. 47.0% occurred within 7d (median 5.4), indicating early failure. The COVID‑19 vaccine had the most reports (n = 24,266) but a weak signal (ROR = 1.25); the Lyme disease vaccine (ROR = 27.81), the rubella vaccine (ROR = 5.69), and the anthrax vaccine (ROR = 3.90) exhibited the strongest signals. Subgroup signals: Lyme disease vaccine except 2021–2026; rubella vaccine only in females/≤17; anthrax vaccine in 18–64. RA‑related vaccine AEs are extremely rare, mainly musculoskeletal and within 1 week. High COVID‑19 volume did not align with its weak signal, while strong signals for the Lyme disease, rubella, and anthrax vaccines reflected specific populations. No strong disproportionality signal was found. However, VAERS is passive, cannot establish causality or confirm safety.