A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta-analysis

Aliment Pharmacol Ther. 2013 Nov;38(10):1255-66. doi: 10.1111/apt.12511. Epub 2013 Oct 5.


Background: Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17% of patients treated with azathioprine. Previous case series have addressed the success rates of re-treatment with mercaptopurine in these individuals.

Aims: To determine the rate of tolerance when trialling mercaptopurine in azathioprine-intolerant patients and the factors predictive of success, and to perform a systematic review and meta-analysis of these data with other published data sets.

Methods: A retrospective observational study of 149 patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis) previously intolerant of azathioprine subsequently treated with mercaptopurine was performed. A meta-analysis was undertaken of all published studies of mercaptopurine use in azathioprine-intolerant patients (455 patients in 11 included studies).

Results: Mercaptopurine was tolerated by 58% of azathioprine-intolerant patients in the Edinburgh cohort. In the meta-analysis, 68% tolerated mercaptopurine. A higher proportion of those in the meta-analysis with GI toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than those with flu-like illness (36%). Among those patients who ceased mercaptopurine for further adverse effects, 59% experienced the same adverse effect as they had with azathioprine.

Conclusions: This meta-analysis shows that switching to mercaptopurine is a safe therapeutic strategy for over two-thirds of azathioprine-intolerant patients and may help optimise immunomodulatory therapy in inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD patients (except those with acute pancreatitis or bone marrow aplasia) before considering thiopurine intolerance.

Publication types

  • Meta-Analysis
  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Azathioprine / adverse effects
  • Azathioprine / therapeutic use
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / drug therapy*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Inflammatory Bowel Diseases / drug therapy
  • Male
  • Mercaptopurine / adverse effects
  • Mercaptopurine / therapeutic use*
  • Middle Aged
  • Retrospective Studies


  • Immunosuppressive Agents
  • Mercaptopurine
  • Azathioprine