Background: Methotrexate, a folate antagonist, is an immunosuppressant drug that is effective for treating several inflammatory disorders including Crohn's disease. Ulcerative colitis, a related chronic inflammatory bowel disease, can be challenging to treat. This review was performed to examine the efficacy of methotrexate for maintenance of remission in ulcerative colitis.
Objectives: To systematically review randomized controlled trials examining the efficacy and safety of methotrexate for maintenance of remission in patients with ulcerative colitis.
Search strategy: The Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane IBD/FBD Review Group Specialized Trials Register, MEDLINE (PUBMED), EMBASE (1984 to November 2008), Web of Science, Scopus, Database of Abstracts of Reviews of Effects (DARE), and Clinical trials database (ClinicalTrials.gov) were searched. In addition, references from selected papers and abstracts from Digestive Disease Week were also examined.
Selection criteria: Only randomized controlled trials (RCT) evaluating the efficacy of methotrexate for maintaining remission in patients with ulcerative colitis compared to placebo or any other intervention were considered for inclusion in this review.
Data collection and analysis: Data were extracted independently by each author. The odds ratio of relapse, 95% confidence interval and P-value were calculated using the Mantel-Haenszel method. An intention to treat analysis was used.
Main results: Only one trial fulfilled the inclusion criteria. This trial randomized 30 patients to methotrexate and 37 to placebo. Methotrexate was given orally in a dose of 12.5 mg/week. Fourteen patients in the methotrexate group and 18 patients in the placebo group who entered remission were followed for 9 months or to the time of first relapse. Sixty-four per cent of methotrexate patients relapsed compared to 44% of placebo patients (OR 2.25; 95% CI 0.54 to 9.45; P = 0.27).
Authors' conclusions: The available evidence is not sufficient to recommend the use of methotrexate to maintain remission in patients with ulcerative colitis. A large scale methodologically rigorous randomized controlled trial is needed. Such a study should investigate higher doses of methotrexate and parenteral administration.