Methotrexate in Crohn's disease: long-term efficacy and toxicity

OBJECTIVE: A 16-wk, placebo-controlled trial has recently shown weekly low- dose methotrexate to be an effective treatment for patients with chronicall y active Crohn's disease. The long-term efficacy and safety of this antimet abolite drug, however, are not yet well established and are assessed in thi s study. METHODS: A total of 49 patients with Crohn's disease who were treated with methotrexate for greater than or equal to 6 months were studied. All patien ts had been chronically treated with steroids; but at the time of initiatio n, only 27 were still on steroids. Of the 49 patients, 42 had previously ta ken azathioprine but were no longer on this drug because of intolerance or failure. Clinical remission was defined as a Harvey-Bradshaw index of <4. RESULTS: In all, 41 patients achieved complete clinical remission and were maintained on methotrexate for a median of 18 months (range, 7-59 months). In these patients the probabilities of relapse were 29%, 41%, and 48% at 1, 2, and 3 yr, respectively. A higher rate of relapse was observed in women and in patients with ileocolitis. Adverse reactions were recorded in 24 pat ients, requiring discontinuation of methotrexate in five. A liver biopsy wa s performed in 11 patients; a mild steatosis was found in five, a slight di lation of the sinusoids in one, a granulomatous hepatitis with a mild porta l fibrosis in one, and a slight periportal fibrosis in one patient. CONCLUSIONS: This study suggests a long-term benefit of maintenance treatme nt with methotrexate in patients with chronically active Crohn's disease, w ith side effects that are usually only moderate. (C) 2000 by Am. Cell. of G astroenterology.