Global burden of vaccine-associated rheumatic diseases and their related vaccines, 1967-2023: A comprehensive analysis of the international pharmacovigilance database

Abstract

Vaccine-associated rheumatic diseases are rare but one of the most feared adverse drug reactions (ADRs). However, this topic has been investigated less with large-scale data in the literature. With the rapid progress in the development and approval of vaccines during the pandemic, public concerns regarding their safety have been raised. To assess the global and regional burden, long-term trends, and potential risk factors of vaccines-associated six types of rheumatic diseases (ankylosing spondylitis [AS], polymyalgia rheumatica [PMR], rheumatoid arthritis [RA], Sjögren's syndrome, Systemic lupus erythematosus [SLE], Systemic scleroderma), this study conducted disproportionality analysis based on the reports from the World Health Organization International Pharmacovigilance Database documented between 1967 and 2023 (n for total reports = 131 255 418) across 156 countries and territories. We estimated the reporting odds ratio (ROR) and information component (IC) to determine the disproportionality signal for rheumatic diseases. Of 198 046 reports of all-cause rheumatic diseases, 14 703 reports of vaccine-associated rheumatic diseases were identified. While the reporting counts have gradually increased over time globally, we observed a dramatic increase in reporting counts after 2020, potentially due to a large portion of reports of COVID-19 mRNA vaccine-associated rheumatic diseases. The disproportionality signal for rheumatic diseases was most pronounced in HBV vaccines (ROR, 4.11; IC₀₂₅, 1.90), followed by COVID-19 mRNA (ROR, 2.79; IC₀₂₅, 1.25), anthrax (ROR, 2.52; IC₀₂₅, 0.76), papillomavirus (ROR, 2.16; IC₀₂₅, 0.95), encephalitis (ROR, 2.01; IC₀₂₅, 0.58), typhoid (ROR, 1.91; IC₀₂₅, 0.44), influenza (ROR, 1.49; IC₀₂₅, 0.46), and HAV vaccines (ROR, 1.41; IC₀₂₅, 0.20). From age- and sex-specific perspective, young females and old males are likely to have vaccine-associated rheumatic disease reports. Furthermore, overall vaccines showed a disproportionality signal for PMR (IC₀₂₅, 3.13) and Sjögren's syndrome (IC₀₂₅, 0.70), systemic scleroderma (IC₀₂₅, 0.64), specifically while the COVID-19 mRNA vaccines are associated with all six types of diseases. Although multiple vaccines are associated with rheumatic disease reports, healthcare providers should be aware of the potential of autoimmune manifestations following vaccination, particularly the COVID-19 mRNA and HBV vaccines, and take into account for risk factors associated with these ADRs. Most ADRs exhibited an average time to onset of 11 days, underscoring the significance of monitoring and timely management by clinicians.

Keywords: Vigibase; autoimmune; rheumatic disease; vaccine.