S955 Differential Risk of Colorectal Cancer in Inflammatory Bowel Disease Patients Treated With Advanced Therapies, Immunomodulators, and 5-Aminosalicylates: A Multi-Research Network Study Utilizing the TrinetX Database

Abstract

Introduction: Colonic inflammation is an established risk factor for Colorectal Cancer (CRC) in IBD. The decrease in CRC risk by modulating underlying inflammation with different mechanistic forms of medical therapy is unclear. We hypothesized that advanced therapy for IBD is chemoprotective. We compared the rates of CRC in patients on different classes of medications. Methods: Clinical data was compiled from the TriNetX database, accessed on April, 14, 2021. TriNetX is a globally federated research network, that provides clinical information from 51 HCOs in the US. Patients with reported ICD-10 codes of K50 (Crohn’s Disease, CD) and K51 (Ulcerative Colitis, UC) from 2005-21, were included. Patients were subdivided into 6 cohorts within each form of IBD (CD, UC), categorized by therapy type: 5-aminosalicylic acid (5-ASA), anti-TNFs (IFX, ADA, GOL, CZP), Immunomodulators (AZA, 6-MP, MTX), tofacitinib (TOF), ustekinumab (USK) and Vedolizumab (VEDO). We evaluated demographics, CRC risk factors, inflammatory markers, IBD-related surgery, behavior and extent. The primary outcome of interest was diagnosis of CRC at least 3 month from therapy initiation. For continuous data, analyses were conducted using independent t-tests. For categorical data, analyses were conducted using chi-square tests. All tests were two-tailed with α=.05. Results: At the time of data collection, 35,243 patients were on therapy for CD and 39,223 patients were on therapy for UC. In the CD cohort, majority of the patients were on 5-ASAs (47.3%) followed by anti-TNFs (28.2%), immunomodulators (18%), USK (3.8%) and VEDO (2.7%). Incidence of CRC at least 3 months after initiation of therapy was lowest for anti-TNFs and USK at 0.45% and 0.44%; followed by VEDO at 0.73% and immunomodulators at 1.03%; and highest for 5-ASA at 1.24%. In the UC cohort, the majority of the patients were on 5-ASAs (86%) followed by immunomodulators (6.3%), anti-TNFs (5.4%), VEDO (1.5%), TOF (0.4%) and USK (0.3%). Incidence of CRC at least 3 months after initiation of therapy was lowest for USK at 0%, followed by VEDO (0.82%), anti-TNFs (0.85%), 5-ASA (1.21%), immunomodulators (1.66%) and TOF at 2.11%. The limitation of the study are small sample size for certain treatments and limited information on IBD phenotypes and disease behavior. Conclusion: In this multi-network database study, the incidence of CRC among CD was lowest for patients on anti-TNFs and highest for patients on 5-ASAs. For UC, incidence of CRC was lowest for patients on biologic therapies.Table 1.: Incidence of Colorectal Cancer (CRC) after at least 3 months of initiation of medication therapy