P1173 - Comparative Impact of Low-Dose Aspirin Alone vs Aspirin Plus Rifaximin on Colorectal Cancer Risk in Ulcerative Colitis With Dysplasia

Allen Luo, MD¹, Allen Seylani, MD², Yohannes Haile, MD², Assal Sadighian, BS², Sadaf Sadighian, BS²
1Keck School of Medicine of the University of Southern California, Moorpark, CA; 2University of California Riverside School of Medicine, Riverside, CA

Introduction: Ulcerative colitis (UC), an inflammatory bowel disease of the colon and rectum, affects about 5 million people worldwide. While the general population has a 10-year cumulative risk of colorectal carcinoma (CRC) of ~0.44%, patients with ulcerative colitis with dysplasia have up to a 39-fold increase in risk. Aspirin has been shown to have efficacy in the chemoprevention of CRC; rifaximin, an antibacterial agent previously used in refractory UC, also has anti-CRC properties. This study seeks to investigate potential synergistic efficacy of these two drugs against CRC risk in patients with UC with dysplasia.

Methods: We performed a retrospective cohort study using anonymized records from the TriNetX platform, comprising over 170 million patients across 145 healthcare organizations in 18 countries. We compared the 5-year CRC incidence in UC patients with dysplasia and refractory disease treated with 1) daily 81-mg aspirin alone or 2) daily 81-mg aspirin plus intermittent rifaximin (200–550 mg for 7–14 days, ≥3 cycles).

Results: In the daily aspirin alone cohort (N=1,869), 24 patients (1.28%) developed CRC, compared to 11 patients (0.54%) in the daily aspirin plus rifaximin cohort (N=1,855). This represents a significant increase in CRC incidence for the aspirin-only group (P=0.017). Patients taking aspirin alone had a 2.382-fold higher risk of CRC compared to those on combination therapy (95% CI, 1.14–4.97). Similarly, the odds of developing CRC were elevated in the aspirin-only group (OR, 2.4).

Discussion: This study demonstrates that adding rifaximin to low-dose aspirin therapy was associated with more than a 2-fold reduction in CRC risk. These findings suggest a synergistic effect between the two drugs. Aspirin acts through COX-2 inhibition, mitigating chronic inflammation and slowing dysplasia progression. Rifaximin significantly and concentration-dependently reduces cell proliferation and migration, downregulates VEGF secretion, nitric oxide release, and the expression of VEGFR-2, MMP-2, and MMP-9. Additionally, rifaximin inhibits phosphorylation of Akt, mTOR, and p38MAPK, and suppresses HIF-1α, p70S6K, and NF-κB signaling. It activates the pregnane X receptor (PXR), inhibiting pro-angiogenic pathways, and may help restore microbial homeostasis while suppressing pro-carcinogenic metabolites. Together, these complementary mechanisms may reduce inflammatory and microbial drivers of colitis-associated tumorigenesis, and therefore, warrant further exploration.

Disclosures:
Allen Luo indicated no relevant financial relationships.
Allen Seylani indicated no relevant financial relationships.
Yohannes Haile indicated no relevant financial relationships.
Assal Sadighian indicated no relevant financial relationships.
Sadaf Sadighian indicated no relevant financial relationships.

Allen Luo, MD¹, Allen Seylani, MD², Yohannes Haile, MD², Assal Sadighian, BS², Sadaf Sadighian, BS². P1173 - Comparative Impact of Low-Dose Aspirin Alone vs Aspirin Plus Rifaximin on Colorectal Cancer Risk in Ulcerative Colitis With Dysplasia, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.