A Cochrane review included 5 studies with a total of 333 subjects.
Intramuscular methotrexate was superior to placebo for maintenance of remission at 40 weeks follow-up. 65% of patients in the intramuscular methotrexate group maintained remission compared to 39% of placebo patients (RR 1.67, 95% CI 1.05 to 2.67; 76 patients). The number needed to treat to prevent one relapse was four.
There was no statistically significant difference in maintenance of remission at 36 weeks follow-up between oral methotrexate (12.5 mg/week) and placebo. 90% of patients in the oral methotrexate group maintained remission compared to 67% of placebo patients (RR 1.67, 95% CI 1.05 to 2.67; 22 patients).
A pooled analysis of two small studies (n = 50) showed no statistically significant difference in continued remission between oral methotrexate (12.5 mg to 15 mg/week) and 6-mercaptopurine (1 mg/kg/day) for maintenance of remission. 77% of methotrexate patients maintained remission compared to 57% of 6-mercaptopurine patients (RR 1.36, 95% CI 0.92 to 2.00).
A pooled analysis of two studies (n = 145) including one high quality trial (n = 126) found no statistically significant difference in maintenance of remission at 36 to 48 weeks between combination therapy (methotrexate and infliximab) and infliximab monotherapy. 54% of patients in the combination therapy group maintained remission compared to 53% of monotherapy patients (RR 1.02, 95% CI 0.76 to 1.38, P = 0.95).
Adverse events were generally mild in nature and resolved upon discontinuation or with folic acid supplementation. Common adverse events included nausea and vomiting, symptoms of a cold, abdominal pain, headache, joint pain or arthralgia, and fatigue.
Intramuscular methotrexate (MTX) (15 mg/week) decreased relapses compared to placebo (OR 0.36, 95% CI 0.15 to 0.87; 1 study, n=76). Oral MTX was used in 2 studies. One study (n=84) compared oral MTX (12.5 mg/week) with 6-MP and placebo and found no statistically significant differences. Another study (n=37) compared oral methotrexate (15 mg/week), 6-MP and 5-ASA and found no statistically significant differences in the maintenance of remission. A pooled analysis (including 1 study, n=76, on intramuscular MTX) showed that methotrexate was significantly more effective than placebo for maintenance of remission in Crohn's disease (OR 3.11, 95% CI 1.31 to 7.41, NNT=4; 2 studies, n=98). There was no difference between methotrexate and 6-MP for maintenance of remission (OR 2.63; 95% CI 0.74 to 9.37; 2 studies, n=50). Adverse events were generally mild in nature and resolved upon discontinuation or with folic acid supplementation. Common adverse events included nausea and vomiting, symptoms of a cold, abdominal pain, headache, joint pain or arthralgia, and fatigue.Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in interventions) and imprecise data (few patients and wide confidence intervals).