Does aspirin worsen Crohn’s disease outcomes? A multicenter propensity-matched cohort study

Background: Aspirin is widely used for cardiovascular prevention, but its safety in Crohn's disease (CD) is unclear. Because CD involves chronic epithelial disruption and impaired mucosal repair, patients may be especially susceptible to aspirin-related injury. This study evaluated the association between aspirin use and major clinical outcomes in a large CD cohort. Methods: Using the TriNetX Network, we identified adults with CD and matched aspirin users 1:1 with nonusers using propensity scores incorporating demographics, comorbidities, and CD severity indicators. The primary outcome was all-cause mortality. Secondary outcomes included CD exacerbations, bowel obstruction, fistula, intestinal abscess, toxic megacolon, colorectal cancer, and colectomy. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Results: Among 376,833 adults with CD, 41,752 aspirin users were matched to 41,752 nonusers. Aspirin use was associated with higher all-cause mortality (RR 1.23) and increased CD exacerbations (RR 1.93). Rates of intestinal abscess (RR 1.32) and toxic megacolon (RR 1.87) were also elevated. No significant differences were observed for colorectal cancer or colectomy. Conclusion: Aspirin use in CD was associated with increased mortality and intestinal morbidity, underscoring the need for individualized prescribing.