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Evidence summaries

Methotrexate for Maintenance of Remission in Crohn's Disease

Intramuscular methotrexate at a dose of 15 mg/week appears to be safe and effective for maintenance of remission in Crohn's disease. Low dose oral methotrexate (12.5 to 15 mg/week) does not appear to be effective for maintenance of remission in Crohn's disease. Level of evidence: "B"

A Cochrane review [Abstract] 1 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.

Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in interventions) and imprecise data (few patients and wide confidence intervals).

    References

    • Patel V, Wang Y, MacDonald JK et al. Methotrexate for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2014;8():CD006884. [PubMed].

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