Methotrexate for maintenance of remission in ulcerative colitis.
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.


OBJECTIVE
To systematically review randomized controlled trials examining the efficacy and safety of methotrexate for maintenance of remission in patients with ulcerative colitis.


METHODS
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.


METHODS
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.


METHODS
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.


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).


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.
El-Matary
Wael
W
Dept. of Pediatrics, Faculty of Medicine, University of Alberta, Aberhart Centre 1, 11402 University Ave, Edmonton, Alberta, Canada, T6G 2J3.
Vandermeer
Ben
B
Griffiths
Anne Marie
AM
D000284:Administration, Oral; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008727:Methotrexate / Q000008:administration & dosage*; D012074:Remission Induction
D007166:Immunosuppressive Agents; D008727:Methotrexate