Risk of lymphoma associated with biologics and immunosuppressants in inflammatory bowel disease patients
Introduction
Current evidence does not allow firm conclusions regarding lymphoma risk across the expanding therapeutic arsenal for inflammatory bowel disease (IBD). We aimed to evaluate lymphoma risk across IBD treatments using a nationwide, population-based database.
Methods
We conducted a nested case–control study within a cohort of all IBD patients 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 IBD duration. Exposures included thiopurines, methotrexate, anti-TNF, vedolizumab, ustekinumab, and JAKi. Adjusted odds ratios (aOR) were estimated using conditional logistic regression, accounting for sociodemographic factors, IBD characteristics, and comorbidities.
Results
Among 422,793 IBD patients, 1,238 lymphoma cases and 52,565 matched controls were included. Current exposures to thiopurines (aOR 2.36, 95%CI: 2.00–2.79) and anti-TNF (aOR 1.72, 95%CI: 1.45–2.05) were associated with increased lymphoma risk. The risk was more than tripled for combination of anti-TNF and thiopurines/methotrexate (aOR 3.44, 95%CI: 2.62–4.51). Risk persisted up to three years after thiopurine discontinuation and one year after anti-TNF discontinuation.
A dose–response relationship was observed for thiopurines. Thiopurines were associated with Hodgkin lymphoma and high-grade non-Hodgkin lymphoma, whereas anti-TNF increased risk across all lymphoma subtypes, including low-grade non-Hodgkin lymphoma.
In contrast, vedolizumab, ustekinumab, and JAKi were not associated with increased lymphoma risk. Methotrexate was associated with increased lymphoma risk, though this association was not consistent across sensitivity analyses.
Conclusion
These findings confirm the increased lymphoma risk associated with thiopurines and anti-TNF in IBD while no increased risk was detected for vedolizumab, ustekinumab, and JAKi.
Meyer, A. et al. (2026), Clinical Gastroenterology and Hepatology