P1285 Risk of lymphoma associated with biologics and immunosuppressants in Inflammatory Bowel Diseases patients: a nationwide nested case-control study

Background Thiopurines and anti-TNF increase the risk of lymphoma in patients with IBD. Data on newer drugs (vedolizumab, ustekinumab, and JAK inhibitors) remain limited due to insufficient sample sizes. Therefore, we aimed to assess the risk of lymphoma associated with biologics and immunosuppressants in patients with IBD. Methods We conducted a nested case–control study within a nationwide IBD cohort identified in the French National Health Data System. Cases were incident lymphomas diagnosed between 2010 and 2024, each matched with up to 50 controls by age, sex, and IBD duration at the case’s diagnosis date (index date). Exposures included thiopurines, methotrexate, anti-TNF, vedolizumab, ustekinumab, and JAK inhibitors. Current exposure was defined as at least one dispensing within 3 months before the index date; recent exposure as treatment discontinued within the past 2 years; past exposure as discontinuation >2 years prior. Adjusted odds ratios (aOR) were estimated using conditional logistic regression, accounting for sociodemographic factors, comorbidities, and IBD characteristics. Results Among 422,793 IBD patients, 33,233 (8.1%) were exposed to methotrexate, 121,427 (29.5%) to thiopurines, 137,656 (33.5%) to anti-TNF, 31,790 (7.7%) to vedolizumab, 32,196 (7.8%) to ustekinumab, and 8,517 (2.1%) to JAK inhibitors. A total of 1,238 lymphoma cases and 52,565 matched controls were included (mean age 59.0 years; 39.4% women). Hodgkin lymphoma represented 15.2% of cases, high-grade non-Hodgkin lymphoma (NHL) 50.6% (38.0% diffuse large B-cell lymphoma), and low-grade NHL 24.8% (10.3% follicular lymphoma). Current thiopurine use was associated with increased lymphoma risk (aOR 2.36, 95%CI: 2.00–2.79), as was recent use (aOR 1.46, 95%CI: 1.13–1.90), but not past use. For anti-TNF, the aOR was 1.72 (95%CI: 1.45–2.05) for current exposure, with no excess risk beyond one year after discontinuation (Figure 1). Thiopurines was associated with Hodgkin lymphoma and high-grade NHL, whereas anti-TNF increased risk across all lymphoma subtypes, including low-grade NHL. Combination therapy with an immunosuppressant and an anti-TNF conferred the highest risk (aOR 3.44, 95%CI: 2.62–4.51). There was a dose-response effect for thiopurines and anti-TNF exposure. No significant excess risk was found for methotrexate, vedolizumab, ustekinumab, or JAK inhibitors. Results were unchanged when analyses were restricted to patients with inactive IBD. Conclusion This nationwide population-based study confirms an increased lymphoma risk associated with thiopurines and anti-TNF, with evidence of dose, subtype-specific effects, and persistence after exposure. No lymphoma risk was observed with vedolizumab, ustekinumab, and JAK inhibitors. Conflict of interest: Dr. Meyer, Antoine: No conflict of interest Weill, Alain: No conflict of interest Carbonnel, Franck: Grant: Alpha Wassermann, Nestlé, Mayoly Spindler Personal Fees: Abbvie, Arena, Biogen, Celltrion, Enterome, Ferring, Janssen, MaaT Pharma, Nestlé, Nordic Pharma, Pierre Fabre, Pharmacosmos, Roche, Takeda, Tillotts, Viatris Dray-Spira, Rosemary: No conflict of interest