Lack of Increased Risk of Lymphoma by Thiopurines or Biologics in Japanese Patients with Inflammatory Bowel Disease: A Large-Scale Administrative Database Analysis

J Crohns Colitis. 2020 Jun 19;14(5):617-623. doi: 10.1093/ecco-jcc/jjz204.

Abstract

Background and aims: Patients with inflammatory bowel diseases may have higher incidences of non-melanoma skin cancers and non-Hodgkin lymphoma, potentially linked to underlying disease and treatments. This analysis assessed incidence rates of these malignancies in Japanese patients with ulcerative colitis or Crohn's disease, and their association with thiopurine and/or anti-tumor necrosis factor-α treatment, using data from a nationwide administrative database in Japan.

Methods: Patients diagnosed with inflammatory bowel disease without malignancy were identified from the Medical Data Vision database. Incident cases of non-melanoma skin cancers and non-Hodgkin lymphoma diagnosed after prescription of thiopurine and/or anti-tumor necrosis factor-α were identified between April 2008 and January 2018. Age- and sex-adjusted incidence rate ratios were calculated relative to the total treated patient population.

Results: A total of 75 673 eligible patients were identified at the index date. Thiopurine prescription with or without anti-tumor necrosis factor-α agents increased incidence rate ratios for non-melanoma skin cancers relative to the overall population (3.39 and 4.03, respectively). There were no notable differences in non-Hodgkin lymphoma incidence relative to the total population in any treatment subgroup, regardless of prescription of thiopurine and/or anti-tumor necrosis factor-α (all incidence rate ratios, ~1).

Conclusions: There is no evidence for an increased incidence of non-Hodgkin lymphoma attributable to thiopurine or anti-tumor necrosis factor-α treatment in Japanese patients with inflammatory bowel disease. The impact of racial differences on non-Hodgkin lymphoma incidences should be considered. Thiopurine therapy may be a risk factor for non-melanoma skin cancers in Japanese patients.

Keywords: Anti-TNFα; immunomodulators; lymphoma; skin cancers.

MeSH terms

  • Adalimumab / therapeutic use
  • Adult
  • Aged
  • Carcinoma, Basal Cell / epidemiology*
  • Carcinoma, Squamous Cell / epidemiology*
  • Colitis, Ulcerative / drug therapy
  • Crohn Disease / drug therapy
  • Cross-Sectional Studies
  • Databases, Factual
  • Drug Therapy, Combination / statistics & numerical data
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Infliximab / therapeutic use
  • Japan / epidemiology
  • Lymphoma, Non-Hodgkin / epidemiology*
  • Male
  • Mercaptopurine / analogs & derivatives
  • Mercaptopurine / therapeutic use
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Skin Neoplasms / epidemiology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Gastrointestinal Agents
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • azathiopurine
  • Infliximab
  • Mercaptopurine
  • Adalimumab