A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators. Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators.
Patients with Crohn's disease often have relapses. Better treatments are needed for the maintenance of remission. Although methotrexate is an effective short-term treatment for Crohn's disease, its role in maintaining remissions is not known.
                We conducted a double-blind, placebo-controlled, multicenter study of patients with chronically active Crohn's disease who had entered remission after 16 to 24 weeks of treatment with 25 mg of methotrexate given intramuscularly once weekly. Patients were randomly assigned to receive either methotrexate at a dose of 15 mg intramuscularly once weekly or placebo for 40 weeks. No other treatments for Crohn's disease were permitted. We compared the efficacy of treatment by analyzing the proportion of patients who remained in remission at week 40. Remission was defined as a score of 150 or less on the Crohn's Disease Activity Index.
                Forty patients received methotrexate, and 36 received placebo. At week 40, 26 patients (65 percent) were in remission in the methotrexate group, as compared with 14 (39 percent) in the placebo group (P=0.04; absolute reduction in the risk of relapse, 26.1 percent; 95 percent confidence interval, 4.4 percent to 47.8 percent). Fewer patients in the methotrexate group than in the placebo group required prednisone for relapse (11 of 40 [28 percent] vs. 21 of 36 [58 percent], P=0.01). None of the patients who received methotrexate had a severe adverse event; one patient in this group withdrew because of nausea.
                In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission. At present only one large controlled study has indicated that parenteral methotrexate may be effective in chronic active Crohn's disease (CD).
                To evaluate the effectiveness of oral methotrexate in chronic steroid-dependent CD.
                Patients with active CD, who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months and with a current Harvey-Bradshaw index of > or = 7 were studied.
                Methotrexate (12.5 mg weekly) or 6-mercaptopurine (50 mg daily), or placebo were given during the 9 months of the trial in addition to steroids and 5-aminosalicylic acid as clinically indicated.
                Eighty-four patients were included (methotrexate, 26 patients; 6-mercaptopurine, 32 patients; placebo, 26 patients). The proportion of patients entering first remission as well as the proportions of patients relapsing after first remission were not significantly different between the groups. The mean Harvey-Bradshaw index and the mean monthly steroid dose were also similar. However, when each patient was evaluated as his or her own control, the reduction in steroid dose, the general well being, and the reduction in abdominal pain were significantly better in the methotrexate treated patients.
                Methotrexate at a weekly oral dose of 12.5 mg was found to be moderately better than 6-mercaptopurine and placebo in patients with chronic active CD. 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.
                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 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 < or = 150 points on the Crohn's Disease Activity Index.
                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.
                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.
Intramuscular methotrexate at a dose of 15 mg/week is safe and effective for maintenance of remission in Crohn's disease. Oral methotrexate (12.5 to 15 mg/week) does not appear to be effective for maintenance of remission in Crohn's disease.