Supplementary Material for: Inflammatory Bowel Disease is Associated with Pericarditis: A Cross-Sectional Study in an NIH-Sponsored, Nationwide Database

Introduction
Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting approximately 2.39 million individuals in the United States. IBD is associated with extraintestinal manifestations (EIMs), among which pericarditis is prominent, comprising 70% of cardiac EIMs. The onset of pericarditis in these patients is primarily attributed to IBD medication-related adverse effects and is predominantly documented through case reports. This highlights the need for an epidemiological study in a large, propensity-matched cohort, given the significant morbidity and mortality of pericarditis.

Methods
Using the National Institutes of Health’s (NIH) All of Us Research Program, we conducted a cross-sectional study and propensity-matched 5,178 IBD cases to 15,534 controls (1:3). We compared demographics, clinical characteristics, prevalence of autoimmune diseases, and rates of pericarditis. Logistic regressions assessed the association between IBD and pericarditis, adjusting for confounders (p < 0.15), and a sensitivity analysis confirmed the association (p < 0.001). A Kaplan-Meier analysis compared the incidence of pericarditis in various IBD severity cohorts, including mild (n=620) and moderate/severe (n=1,908), stratified by IBD medication exposure.

Results
Pericarditis was significantly more prevalent in IBD cases (1.3% vs. 0.6%; absolute risk difference (ARD) 0.7%, 95% confidence interval (CI) 0.37%–1.03%), with significant associations in univariable (odds ratio (OR) 2.2, 95% CI 1.6–3.0, p < 0.001) and multivariable analyses (OR 1.9, 95% CI 1.3–2.6, p < 0.001). IBD preceded pericarditis in 65% of cases. There was no difference in pericarditis-free survival between mild and moderate/severe cohorts (p = 0.90).

Conclusion
This study uniquely provides evidence of a significant association between IBD and pericarditis, establishing pericarditis as a clinically significant EIM in a large, diverse U.S. cohort, independent of disease severity. This highlights the need for heightened screening to enhance pericarditis management and patient outcomes.