Azathioprine in inflammatory bowel disease: improved molecular insights and resulting clinical implications

Abstract

Azathioprine and 6-mercaptopurine represent important first-line immunosuppressive drugs in the treatment of inflammatory bowel disease. Owing to 45 years of clinical experience with thiopurines in inflammatory bowel disease, there currently exist strong data from numerous clinical trials and meta-analyses, which clearly document the therapeutic efficacy of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease. However, the exact molecular mechanism of action of these drugs was insufficiently understood for a long time. During the last few years, important new insights into the intracellular effects of azathioprine have been gained and thiopurines have been identified as strong inducers of T-cell apoptosis. This article aims to summarize traditional and current concepts of azathioprine-mediated effects and endeavors to discuss the resulting clinical implications.

Keywords::

• 6-mercaptopurine
• 6-thio-GTP
• apoptosis
• azathioprine
• inflammatory bowel disease

Financial & competing interests disclosure

Markus F Neurath and Imke Atreya hereby disclose that they are currently working on a project about azathioprine and chemically modified 6-thio-GTP analogues, which was and is still financially supported by Giuliani Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.