Lack of Increased Risk of Lymphoma with Thiopurine Therapy Regardless of Dose and Duration of Treatment in Japanese Patients with Inflammatory Bowel Diseases

Abstract

Background: Immunomodulator therapy (e.g., thiopurines) has been linked to an increased malignancy risk, in patients with inflammatory bowel diseases (IBDs), which increases with treatment duration, based on studies mainly in Caucasian patients. However, our previous real-world study, of Japanese patients with IBDs, indicated no overall increased risk of non-Hodgkin lymphoma (NHL) with thiopurine treatment.

Objectives: This subanalysis investigated the influence of thiopurine IBD treatment dose and duration, on incidence of NHL in Japanese patients.

Method: The Medical Data Vision (MDV) claims database (17.8 million patients; April 2008-January 2018) was used to analyze incidence rate ratios (IRRs) of NHL, in eligible patients (≥1 diagnosis of ulcerative colitis or Crohn's disease) and no malignancy at diagnosis or first prescription of a thiopurine. Age- and sex-adjusted IRRs and 95% confidence interval for NHL were calculated as the incident cases compared in the subgroups versus the overall IBD population.

Results: Among 75,673 patients with IBDs, 103 cases of NHL were recorded. There was no overall increase in the risk of developing NHL among Japanese patients treated with thiopurines. The IRRs relative to the overall IBD population were 1.88, 1.42, and 0.38 for <1 year, 1-3 years, and ≥3 years of thiopurine treatment. There were no differences in NHL incidence when grouping patients by mean daily thiopurine dose prescribed, age, or disease subgroups.

Conclusion: Dose or duration of thiopurine treatment did not explain a lack of increased risk of NHL with thiopurine use in Japanese patients with IBDs.

Keywords: Inflammatory bowel disease; Lymphoma risk; Thiopurine.