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Previous Volume 332:292-297 February 2, 1995 Number 5 Next

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ABSTRACT

Background Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are unsuccessful.

Methods We conducted a double-blind, placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn's disease despite a minimum of three months of prednisone therapy. Patients were randomly assigned to treatment with intramuscular methotrexate (25 mg once weekly) or placebo for 16 weeks. The patients also received prednisone (20 mg once a day), which was tapered over a period of 10 weeks unless their condition worsened. The primary outcome measure was clinical remission at the end of the 16-week trial. Remission was defined by the discontinuation of prednisone and a score of <150 points on the Crohn's Disease Activity Index.

Results A total of 141 patients were randomly assigned in a 2:1 ratio to methotrexate (94 patients) or placebo (47 patients). After 16 weeks, 37 patients (39.4 percent) were in clinical remission in the methotrexate group, as compared with 9 patients (19.1 percent) in the placebo group (P = 0.025; relative risk, 1.95; 95 percent confidence interval, 1.09 to 3.48). The patients in the methotrexate group received less prednisone overall than those in the placebo group (P = 0.026). The mean (±SE) score on the Crohn's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group (162±12) than in the placebo group (204±17, P = 0.002). The changes in quality-of-life scores and serum orosomucoid concentrations were similar. In the methotrexate group, 16 patients (17 percent) withdrew from treatment because of adverse events (including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6), as compared with 1 patient (2 percent) in the placebo group.

Conclusions In a group of patients with chronically active Crohn's disease, methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone.

Source Information

From the Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, Alta. (L.S.); the Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago (S.B.H.); the Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton (R.N.F.); the Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Ont. (E.J.I.); the Departments of Medicine (B.G.F., J.W.D.M., M.H.) and Epidemiology and Biostatistics (B.G.F., J.R.), University of Western Ontario, London, Ont.; the Department of Medicine, Division of Gastroenterology, McGill University, Montreal (G.W.); the Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto (A.H.S., G.R.G.); and the Department of Medicine, University of Ottawa, Ottawa, Ont. (R.G.).

Address reprint requests to Dr. Feagan at 6 OF 12 University Hospital, 339 Windemere Rd., London, ON N6A 5A5, Canada.

Full Text of this Article

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