Methotrexate: should we start using it in clinical practice?

Therapeutic approaches in inflammatory bowel disease have changed significantly in the past decade. Early aggressive immunosuppression has become the mainstay of therapy for patients at risk for complicated disease. Azathioprine is the most widely used immunosuppressant; however, a subgroup of patients is intolerant or refractory. Since the late 1990s, methotrexate (MTX) has become more widely used as an immunomodulator in patients with chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. Yet according to recent clinical data, methotrexate remained the second most commonly used immunosuppressive in inflammatory bowel diseases. Two landmark trials and subsequent studies provided evidence for the use of methotrexate in Crohn's disease, both for induction and maintenance of remission. The evidence is less solid in ulcerative colitis, for which results of further randomized controlled trials are pending (e.g. Meteor, Merit). A potential new indication of MTX could be combination therapy with biologicals. While this is state of the art therapy in rheumatoid arthritis, data in inflammatory bowel diseases are less clear. Some studies suggest that combination with immunosuppressants could prevent the development of anti-drug antibodies, while others suggested anti- TNF induced autoimmune disorders as a potential indication. In contrast, improved efficacy was not reported by one study (COMMIT). Limitations include frequent side effects, route of administration, pregnancy and concerns about long-term safety. This review summarizes current knowledge on the efficacy and side effects of methotrexate, and tries to reevaluate the drug in the current IBD armamentarium.