Methotrexate for maintenance of remission in Crohn's disease.
BACKGROUND
Safe and effective long-term treatments that reduce the need for corticosteroids are needed for Crohn's disease. Although purine antimetabolites are moderately effective for maintenance of remission patients often relapse despite treatment with these agents. Methotrexate may provide a safe and effective alternative to more expensive maintenance treatment with TNF-alpha antagonists.


OBJECTIVE
To conduct a systematic review of randomized trials examining the efficacy and safety of methotrexate for maintenance of remission in Crohn's disease.


METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009, PUBMED (1966 to April 2009), EMBASE (1984 to April 2009), DDW abstracts (1980 to 2008) and the Cochrane IBD/FBD Specialized Trials Register were searched. Study references and review papers were also searched for additional trials.


METHODS
Randomised controlled trials (RCTs) that compared methotrexate to placebo or any other active intervention for maintenance of remission in Crohn's disease were eligible for inclusion.


METHODS
Data extraction and assessment of methodological quality of included studies were independently performed by each author. The main outcome measure was the proportion of patients maintaining clinical remission as defined by the studies and expressed as a percentage of the total number of patients randomized (intention to treat analysis). Pooled odds ratios and 95% confidence intervals were calculated for dichotomous outcomes.


RESULTS
Three studies were included in the review. A pooled analysis (n = 98) including one high quality trail (n = 76) showed that intramuscular methotrexate (15 mg/week) was significantly more effective than placebo for maintenance of remission in Crohn's disease (OR 3.11; 95% CI 1.31 to 7.41; P = 0.01). The number needed to treat to prevent one relapse was 4. A pooled analysis of two small studies (n = 50) showed no difference between methotrexate and 6-MP for maintenance of remission (OR 2.63; 95% CI 0.74 to 9.37; P = 0.14). 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.


CONCLUSIONS
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.
Patel
Vishal
V
LHSC - South Street Hospital, Mailbox 55, 375 South Street, London, Ontario, Canada, N6A 4G5.
Macdonald
John K
JK
McDonald
John Wd
JW
Chande
Nilesh
N
D000284:Administration, Oral; D003424:Crohn Disease / Q000188:drug therapy*; D004334:Drug Administration Schedule; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007273:Injections, Intramuscular; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction
D007166:Immunosuppressive Agents; D008727:Methotrexate