Thiopurines Treatment for Inflammatory Bowel Disease in Current Clinical Practice

Thiopurines, or purine analogues, are immunomodulators used in the treatment of malignancies, rheumatic diseases, dermatologic conditions, inflammatory bowel disease and in solid organ transplantation. These agents include azathioprine (AZA), mercaptopurine (6-MP) and thioguanine (6- TG). Thiopurines are converted by the enzyme thiopurine methyltransferase (TPMT) into metabolites. Measurement of TPMT activity may help identify patients at risk for excessive toxicity, most often myelosuppression, after receiving standard doses of thiopurine medications. Measurement of metabolites (metabolite markers) may help tailor individualized drug therapy. Azathioprine, which is a prodrug of 6-mercaptopurine (6-MP), is considered an effective immunosuppressive treatment of inflammatory bowel disease, particularly in patients with steroid- resistant disease. For example, in the course of 1 year, 50% of patients with Crohn’s disease will require steroids for its treatment; of these, 50% will either be steroid resistant or steroid dependent, and thus candidates for immunosuppressive therapy. Azathioprine therapy eliminates the need for corticosteroids in about 75% of patients; azathioprine is also considered an effective therapy for fistulizing disease. Results: A recent randomized clinical trial of children with Crohn’s disease suggests that compared to prednisone alone, the inclusion of azathioprine with prednisone at the time of initial diagnosis is associated with improved maintenance of remission, while simultaneously decreasing the dose of prednisone. However, the use of azathioprine is limited by both its long onset of action (3–4 months) and drug toxicities, which include hepatotoxicity, bone marrow suppression, pancreatitis and allergic reactions. Long-term drug use has been associated with neoplasia. Objective: The purpose of this comprehensive review is to suggest guidelines for the application of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease.