Risk of Lymphoma Associated With Biologics and Immunosuppressants in Inflammatory Bowel Disease Patients: A...

Current evidence does not allow firm conclusions regarding lymphoma risk across the expanding therapeutic arsenal for inflammatory bowel disease. We aimed to evaluate lymphoma risk across inflammatory bowel disease treatments using a nationwide, population-based database.

We conducted a nested case-control study within a cohort of all patients with inflammatory bowel disease recorded in the French National Health Data System (SNDS) between 2009 and 2024. Incident lymphoma cases were matched to up to 50 controls by calendar year, age, sex, and inflammatory bowel disease duration. Exposures included thiopurines, methotrexate, anti-tumor necrosis factors, vedolizumab, ustekinumab, and Janus kinase inhibitors. Adjusted odds ratios were estimated using conditional logistic regression, accounting for sociodemographic factors, inflammatory bowel disease characteristics, and comorbidities.

Among 422,793 patients with inflammatory bowel disease, 1238 lymphoma cases and 52,565 matched controls were included. Current exposures to thiopurines (adjusted odds ratio, 2.36; 95% confidence interval, 2.00-2.79) and anti-tumor necrosis factors (adjusted odds ratio, 1.72; 95% confidence interval, 1.45-2.05) were associated with increased lymphoma risk. The risk was more than tripled for combination of anti-tumor necrosis factors and thiopurines/methotrexate (adjusted odds ratio, 3.44; 95% confidence interval, 2.62-4.51). Risk persisted up to 3 years after thiopurine discontinuation and 1 year after anti-tumor necrosis factor discontinuation. A dose-response relationship was observed for thiopurines. Thiopurines were associated with Hodgkin lymphoma and high-grade non-Hodgkin lymphoma, whereas anti-tumor necrosis factors increased risk across all lymphoma subtypes, including low-grade non-Hodgkin lymphoma. In contrast, vedolizumab, ustekinumab, and Janus kinase inhibitors were not associated with increased lymphoma risk. Methotrexate was associated with increased lymphoma risk, although this association was not consistent across sensitivity analyses.

These findings confirm the increased lymphoma risk associated with thiopurines and anti-tumor necrosis factors in inflammatory bowel disease, whereas no increased risk was detected for vedolizumab, ustekinumab, and Janus kinase inhibitors.