Update on the Use of Thiopurines and Methotrexate in Inflammatory Bowel Disease

The increased use of biologic agents over the past two decades has led to a reappraisal of the role of the immunomodulators (thiopurines and methotrexate) in the treatment of inflammatory bowel disease. The purpose of this review is to summarize recent data on the use of thiopurines and methotrexate either as monotherapy or as part of combination therapy with biologic agents.

Recent studies have addressed the need for concomitant immunomodulatory therapy in treatment-naïve patients starting anti-TNF-α therapy, the appropriate dose of the immunomodulator in this setting, the minimum duration of combination therapy, and the possible mechanisms by which immunomodulators enhance the effectiveness of anti-TNF-α agents. Little is known about the role of immunomodulators in combination with agents belonging to other classes of biologic therapies. Recent studies have shown that methotrexate is not effective in inducing or maintaining remission in ulcerative colitis. Finally, several studies have broadened our understanding of the infection and malignancy risks of the immunomodulators. Immunomodulators continue to have a place in the treatment of inflammatory bowel disease. However, with the ever-increasing list of biologic agents, properly positioning the immunomodulators within the overall therapeutic scheme is a complicated task. In order to optimize outcomes, each patient requires an individualized approach, which takes into account risks, benefits, cost, alternatives, and patient preferences.