Crohn's disease is a chronic inflammatory disease of the intestines that frequently occurs in the lower part of the small intestine, called the ileum. However, Crohn’s disease can affect any part of the digestive tract, from the mouth to the anus. The most common symptoms are abdominal pain and diarrhea. Prevention of clinical relapse (resumption of symptoms of active disease) in patients in remission is an important objective in the management of Crohn’s disease. Methotrexate is a drug that suppresses the body's natural immune responses and may suppress inflammation associated with Crohn’s disease. The purpose of this systematic review was to examine the effectiveness and side effects of methotrexate used to maintain remission in Crohn's patients.
This review identified five studies that included a total of 333 participants. Two studies compared methotrexate (administered by pill or intramuscular injection) to a placebo (a sugar pill or a saline injection). One of these two studies also compared methotrexate to 6-mercaptopurine (an immunosuppressive drug). One small study compared methotrexate to both 6-mercaptopurine and 5-aminosalicylic acid (an anti-inflammatory drug). Two studies compared combination therapy with methotrexate and infliximab (a biological drug that is a tumour necrosis factor-alpha antagonist) to infliximab used by itself. One high quality study (76 patients) shows that methotrexate (15 mg/week) injected intramuscularly (i.e. into muscles located in the arm or thigh) for 40 weeks is superior to placebo for preventing relapse (return of disease symptoms) among patients whose disease became inactive while taking higher doses of intramuscular methotrexate (25 mg/week). Side effects occurred in a small number of patients. These side effects are usually mild in nature and include nausea and vomiting, cold symptoms, abdominal pain, headache, joint pain and fatigue. One small study (22 patients) found no difference in continued remission between low dose methotrexate (12.5 mg/week) taken orally and placebo and suggests that low dose oral methotrexate is not an effective treatment for inactive Crohn's disease. However this result is uncertain due to the small number of patients assessed in the study. Large-scale studies of methotrexate given orally at higher doses for maintenance of remission in Crohn’s disease may provide stronger evidence for the use of methotrexate in this manner. A pooled analysis of two studies (50 patients) found no difference in continued remission between oral methotrexate (12.5 to 15 mg/week) and 6-mercaptopurine (1 mg/kg/day). No firm conclusions can be drawn as these results are uncertain due to poor study quality and small numbers of patients. A small study (13 patients) found no difference in continued remission between methotrexate and 5-aminosalicylic acid. No conclusions can be drawn from this study as the results are very uncertain due to poor study quality and small numbers of patients. A pooled analysis of two studies (145 patients) found no difference in continued remission between combination therapy and infliximab. Combination therapy with methotrexate and infliximab does not appear to be any more effective for maintenance of remission than infliximab used by itself. This result is uncertain because one study was of poor quality (the other was high quality) and small numbers of patients.