Reduced risk of colorectal cancer with non-sulfasalazine 5-ASAs in ulcerative colitis and Crohn’s disease and anti-TNF therapy in ulcerative colitis: a systematic review and meta-analysis

Journal article

Objective: The incidence of colorectal cancer (CRC) remains elevated in the inflammatory bowel disease (IBD) population. We aimed to examine the association of biologics, 5-aminosalicylates (5-ASAs) and immunomodulators with the risk of CRC and/or dysplasia (CRC/Dys) in different IBD phenotypes. Methods: We searched Web of Science, PubMed, MEDLINE and EMBASE from inception to 15 March 2025 for all studies assessing the association of biologics, 5-ASAs and immunomodulators on the occurrence of CRC/Dys in adults (≥16 years) with IBD. No randomised controlled trials were identified. Data were pooled using a random effects model generating relative risk (RR) estimates. Results: Fifty observational studies containing 29 325 cases of CRC/Dys in 1 434 939 patients with IBD were included. Biologic therapies (RR 0.74; 95% CI 0.64 to 0.85, I2=56.8%) and 5-ASAs (RR 0.78; 95% CI 0.70 to 0.86, I2=52.1%) were associated with a reduced risk of CRC/Dys in patients with IBD. Immunomodulators were not associated with a reduced risk (RR 0.92; 95% CI 0.82 to 1.02, I2=82.7%). After stratification for IBD phenotypes, medication subgroups and CRC outcome, anti-tumour necrosis factor (anti-TNF) therapies were associated with a reduced risk of CRC in patients with ulcerative colitis (RR 0.78; 95% CI 0.73 to 0.83, I2=0%) but not in Crohn’s disease. Non-sulfasalazine 5-ASAs were associated with a reduced risk of CRC in ulcerative colitis (RR 0.66; 95% CI 0.45 to 0.96, I2=75.4%) and Crohn’s disease (RR 0.84; 95% CI 0.81 to 0.87, I2=41.9%). Conclusion: Use of anti-TNF biologics or non-sulfasalazine 5-ASAs is associated with a reduction in CRC risk in IBD, with differential effects by IBD phenotype. PROSPERO registration number: CRD42024559501.

Authors: Kefayat, A; Porter, RJ; Churchhouse, AM; Blackwell, J; Watson, EF

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BMJ Publishing Group
• Journal: Frontline Gastroenterology
• Pages: flgastro-2025-103409
• Article number: flgastro-2025-103409
• Publication date: 2025-12-04
• Acceptance date: 2025-11-02
• DOI: 10.1136/flgastro-2025-103409
• EISSN: 2041-4145
• ISSN: 2041-4137
• Language: English
• Keywords: Inflammatory Bowel Disease; Chemoprevention; 5-Aminosalicylic Acid (5-ASA); Colorectal Cancer