Toxicity profile of thiopurines in inflammatory bowel disease: a retrospective cohort analysis

Tunis Med. 2020 May;98(5):404-412.


Background: Thiopurines have proven efficacy in inflammatory bowel disease. However, their use is limited by adverse effects in a subset of patients.

Aims: The present study aimed to evaluate toxicity profile and identify clinical predictive factors of thiopurine adverse effects in inflammatory bowel disease patients.

Methods: A retrospective longitudinal study was conducted among inflammatory bowel disease patients treated with thiopurines. Multiple logistic regression was used to identify risk factors for thiopurine adverse effects.

Results: A total of 210 patients were enrolled in the study. Mean age at disease onset was 29.8±11.4 years. One hundred sixty-nine (169) patients had Crohn's disease, 29 had ulcerative colitis and 12 had indeterminate colitis. During a median follow-up of 28.5 ± 20 months, 56 patients (26.6%) had thiopurine-related adverse effects including digestive intolerance (n=14; 6.6%), immunoallergic reactions (n=8; 3.8%), myelotoxicity (n=25; 11.9%) and hepatotoxicity (n=8; 3.8%). Treatment withdrawal was reported in 19 patients (9%). The only independent predictive factor for thiopurine adverse effects found in this study was steroid-dependence (OR= 3.96; 95% CI: 1.07- 14.53; p= 0.038).

Conclusions: Almost a quarter of inflammatory bowel disease patients treated with thiopurines developed adverse effects. These adverse effects lead to drug withdrawal in almost 9% of patients either as monotherapy or as in combination with biologic therapies. Steroid-dependent patients were significantly at higher risk for thiopurine-related toxicity.

MeSH terms

  • Adolescent
  • Adult
  • Azathioprine / adverse effects
  • Azathioprine / therapeutic use
  • Cohort Studies
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / epidemiology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Purines / adverse effects
  • Purines / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Young Adult


  • Immunosuppressive Agents
  • Purines
  • Azathioprine