M Housam Nanah, MD1, Varun Aitharaju, MD2, Ahmed Telbany, MD3, Joseph Sleiman, MD2 1Cleveland Clinic, Cleveland, OH; 2Cleveland Clinic Foundation, Cleveland, OH; 3University of New Mexico, Albuquerque, NM Introduction: Inflammatory bowel disease (IBD), has been linked with lymphoma, particularly through the use of an immunosuppressant agent (IMM), azathioprine (AZA), with or without biologics. Many consider methotrexate (MTX) as an alternative, safer, immunosuppressive agent for combination therapy. However, some evidence in non-IBD autoimmune disorders suggests a similar lymphoma risk. This study investigates the relationship between AZA or MTX use and the incidence of lymphoma and all-cause mortality in the IBD patient population. Methods: In this retrospective cross-sectional TriNetX database study, adult patients with ulcerative colitis (UC) and Crohn’s disease (CD) were identified using ICD-10 codes, and 4 cohorts were established: Patients with IBD on either MTX or AZA (IBD+IMM), those with no exposure to MTX or AZA (IBD-IMM), IBD patients with IBD only AZA exposure (IBD+AZA), and those with only MTX exposure (IBD+MTX). Propensity score matching (PSM) was performed based on baseline demographics, age, and sex, and use of advanced IBD therapies. Results: PSM yielded 18,308 patients in both groups of IBD+IMM and IBD-IMM. Similarly, 7,749 patients were identified for comparing groups of IBD+AZA and IBD+MTX.
Following PSM, IBD+IMM had lower odds of mortality (OR 0.725) and higher odds of Burkitt’s lymphoma (OR 3.59) compared to patients of IBD-IMM. IBD+AZA group had lower odds of mortality (OR 0.865) with no difference in terms of lymphoma development compared to patients with IBD+ MTX. Discussion: In this large, real-world cross-sectional study, the use of IMMs in patients with IBD was associated with lower mortality odds at the risk of an increased risk of developing Burkitt’s lymphoma. This might portray the balance between benefits of disease control and IMM risk. However, analysis comparing MTX to AZA did not show a signal against either agent for lymphoma, which suggests caution with both agents as opposed to AZA alone.
Figure: Baseline characteristics after PSM
Figure: Outcomes after PSM
Disclosures: M Housam Nanah indicated no relevant financial relationships. Varun Aitharaju indicated no relevant financial relationships. Ahmed Telbany indicated no relevant financial relationships. Joseph Sleiman indicated no relevant financial relationships.
M Housam Nanah, MD1, Varun Aitharaju, MD2, Ahmed Telbany, MD3, Joseph Sleiman, MD2. P3285 - Assessing the Outcomes of AZA and MTX Use on Mortality and Lymphoma Development in Patients With IBD, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.