Increasing risk of lymphoma over time in Crohn's disease but not in ulcerative colitis : a Scandinavian cohort study

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD) but have often been limited by detection biases, (especially during the first year of follow-up), misclassification, and small sample size; and rarely reflect modern-day management of IBD. METHODS: Binational register-based cohort study (Sweden and Denmark) during 1969-2019. We compared 164,716 patients with IBD to 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up. RESULTS: During 1969-2019, 258 patients with Crohn's Disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35(CD) and 34(UC)/100,000 person-years [PY] in IBD patients, compared to 28 and 33/100,000 PY in their matched reference individuals. While both CD (HR=1.32; 95%CI=1.16-1.50) and UC (HR=1.09; 95%CI=1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95%CI=0.02 to 0.13])). HRs increased the past two decades, corresponding to increasing use of immunomodulators and biologics during the same time-period. HRs were increased for aggressive B-cell NHL in CD and UC patients, and for T-cell NHL in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second line biologics, we also found increased HRs in patients naïve to such drugs. CONCLUSIONS: During the past 20 years, HRs for lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.
Supported by Swedish Medical Society grant Dnr SLS-789611, the Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Läkarutbildning och Forskning (ALF) grants Dnr 20170720 and 20190638, and the Swedish Research Council grant Dnr 2020-02002 (O.O.) ; by the Swedish Cancer Society, the Stockholm County Council (ALF) , the Swedish Research Council, and the Swedish Foundation for Strategic Research during the conduct of the study (J.A.) ; by a grant from the Independent Research Fund Denmark (H.T.S.) ; and by the Forskningsrådet for hälsa, arbetsliv och välfärd Foundation and the Swedish Cancer Foundation (J.F.L.) .