DOP130Angiotensin receptor blockers are associated with reduced risk of fibrostenotic complications of Crohn’s disease in a large propensity score-matched study

Background Fibrostenotic complications represent a significant unmet therapeutic need in Crohn’s disease (CD), affecting up to 50% of patients and often necessitating surgery due to the current lack of antifibrotic medications.1Experimental evidence implicates the renin-angiotensin-aldosterone system (RAAS) in intestinal fibrosis, and studies demonstrate that RAAS inhibitors, such as angiotensin II receptor blockers (ARBs), improve outcomes in animal models of CD.2 However, these findings lack consistent clinical validation. We aimed to evaluate whether ARBs or angiotensin-converting enzyme inhibitors (ACEis) are associated with a reduced risk of fibrostenotic complications in patients with CD. Methods We performed a retrospective study using the multi-institutional database TriNetX comparing rates of endoscopic balloon dilation, stricturoplasty, and ileal/ileocolic resection–proxies for fibrotic complications–in CD patients taking ARBs or ACEis to those not taking them. One-to-one propensity score matching (PSM) was performed to balance cohorts by age, sex, race, smoking status, and comorbidities, including hypertension and type 2 diabetes. Medication exposure required ≥5 prescriptions, including a second prescription within 1 and 6 months of the first. Risks were expressed as hazard ratios (HR) and Kaplan-Meier curves. Results We identified 232,349 adults with CD. Demographics and clinical characteristics are reported in Table 1. After PSM, 8,656 CD patients taking ARBs (mean age 60.7±13 years; 53% female; 75% White) were compared to an equal number not taking ARBs. ARB use was associated with a 24% lower risk of intervention (HR: 0.76, 95% CI: 0.68-0.84, P<0.01). In contrast, ACEis did not reduce fibrostenotic complications (N=9,272, HR: 1.02, 95% CI: 0.93-1.12, P=0.65) (Figures A, B, E). These results are consistent with the selective blockade of AT1R by ARBs, which reduces pro-fibrotic and inflammatory signaling while preserving AT2R-mediated protective pathways. In contrast, ACEis suppress both AT1R and AT2R signaling and increase renin and bradykinin, which may offset their anti-fibrotic potential. Secondary analyses showed that CD patients taking losartan had a 26% lower risk of intervention (N=6,104, HR: 0.74, 95% CI: 0.65-0.84, P<0.01), with higher doses (≥50 mg) conferring an even greater benefit (N=1,748, HR: 0.61, 95% CI: 0.48-0.79, P<0.01) (Figures C-E). Conclusion ARB use is associated with reduced endoscopic or surgical interventions for CD-associated fibrosis, with evidence of dose dependence. These findings support a potential antifibrotic mechanism for ARBs and warrant further prospective clinical evaluation of their repurposing for the prevention of fibrostenotic complications in CD. References: 1.Rieder F, Mukherjee PK, Massey WJ, et al. Fibrosis in IBD: from pathogenesis to therapeutic targets. Gut 2024 2.Artone S, Ray S, Williams JJ, et al. The angiotensin receptor blocker, losartan, reduces inflammation and fibrosis, and prevents relapse of fibrosis after steroid-induced remission, in mice prone to Crohn’s disease-like ileitis. J Crohns Colitis 2025;19:jjaf083. Conflict of interest: Srivastava, Anusha: I have no conflict of interest to disclose. Parigi, Tommaso Lorenzo: No conflict of interest Perez, Jaime: None Pizarro, Theresa: No conflict of interest