S1598 Predictors of Risk of Lymphoma in IBD Patients With Thiopurine Use: A Retrospective TrinetX Based Study

Introduction: Thiopurines (azathioprine and mercaptopurine) are effective for maintenance of remission in ulcerative colitis (UC), particularly in patients who are steroid-dependent or intolerant to mesalamine. The risk of developing lymphoma in patients with ulcerative colitis treated with thiopurines is increased. Methods: We performed a retrospective cohort study via TriNetX, with 2 cohorts using the platform: patients with ulcerative colitis who received thiopurines, and those with UC who had no record of thiopurine use. We excluded patients with a prior history of lymphoma, crohn’s disease, HIV infection, organ transplantation, and other biologic use. Only adults aged ≥18 years were included. Propensity score matching (1:1) balanced baseline covariates (age, sex, disease duration, co-medications) between exposed and unexposed groups. The primary outcome was incident lymphoma (any subtype) after UC diagnosis. Time-to-event analyses were used to compare lymphoma risk, yielding hazard ratios (HR) with 95% confidence intervals (CI). Results: In a matched cohort of 13,562 ulcerative colitis patients with thiopurine exposure and 13,567 unexposed patients, lymphoma occurred in 23 and 11 cases, respectively. Kaplan-Meier analysis showed high 5-year lymphoma-free survival probabilities (98.49% vs 99.84%), with median survival not reached in either group. The log-rank test (χ² = 2.053, P = 0.152) and hazard ratio (HR = 1.68, 95% CI: 0.82–3.46; P = 0.066) indicated no statistically significant increased lymphoma risk with thiopurines, though a numerical trend toward higher risk was observed. Lymphoma risk was doubled in thiopurine group (0.4% vs 0.2%, HR 1.6, P = 0.047). Conclusion: Thiopurines (azathioprine and mercaptopurine) are effective for maintenance of remission in ulcerative colitis, particularly in patients who are steroid-dependent or intolerant to mesalamine. This risk is highest during active therapy and decreases after discontinuation. Hence, Careful patient selection and monitoring are essential: pre-treatment screening for TPMT and NUDT15 deficiency is recommended to reduce the risk of myelosuppression, and ongoing monitoring for cytopenias, hepatotoxicity, and malignancy is required.