Is there a role for thioguanine therapy in IBD in 2017 and beyond?

Expert Rev Gastroenterol Hepatol. 2017 May;11(5):473-486. doi: 10.1080/17474124.2017.1294062. Epub 2017 Feb 20.

Abstract

Conventional thiopurines are effective for the maintenance of remission of Crohn's disease and ulcerative colitis, however, up to half of patients are intolerant or unresponsive to these medications. Thioguanine is an alternative thiopurine that has shown efficacy in inflammatory bowel disease, and is particularly useful to circumvent certain side effects associated with conventional thiopurines, for example, pancreatitis. Its association with nodular regenerative hyperplasia of the liver has hindered its widespread use. Areas covered: We aim to outline the rational use of thioguanine, including safety monitoring, with particular regard to hepatotoxicity. A literature search was performed: PubMed was searched for full papers and abstracts published in English since January 2000 using the following terms, alone and in combination: 'azathioprine', 'thiopurine', 'Crohn's disease', 'inflammatory bowel disease', 'nodular regenerative hyperplasia', 'mercaptopurine', 'thioguanine', 'ulcerative colitis'. Further relevant papers were identified from the reference lists of selected papers. Expert commentary: Despite optimisation strategies such as metabolite measurements and the use of allopurinol, a significant proportion of patients will remain intolerant to thiopurines, especially those with allergic reactions, including pancreatitis. For this subgroup of patients we suggest that low dose thioguanine is an alternative to other therapies that are either parenteral or expensive.

Keywords: Azathioprine; conventional thiopurines; crohn’s disease; inflammatory bowel disease; mercaptopurine; nodular regenerative hyperplasia; thioguanine; ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimetabolites / adverse effects
  • Antimetabolites / therapeutic use*
  • Chemical and Drug Induced Liver Injury / etiology
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / diagnosis
  • Crohn Disease / drug therapy*
  • Drug Monitoring
  • Focal Nodular Hyperplasia / chemically induced
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Pancreatitis / chemically induced
  • Risk Factors
  • Thioguanine / adverse effects
  • Thioguanine / therapeutic use*
  • Treatment Outcome

Substances

  • Antimetabolites
  • Gastrointestinal Agents
  • Thioguanine