Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease.
BACKGROUND
The therapeutic role of 6-mercaptopurine and azathioprine remains controversial due to their perceived relatively slow-acting effect and adverse effects. A meta-analysis was performed to evaluate the efficacy of these agents for the maintenance of remission of quiescent Crohn's disease.


OBJECTIVE
To assess the efficacy of azathioprine and 6-mercaptopurine for maintenance of remission in quiescent Crohn's disease.


METHODS
Pertinent studies were selected using the MEDLINE data base (1966-May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease register, as well as abstracts from major gastrointestinal research meetings and references from published articles and review. This search strategy was updated (1998-May 2008) using the MEDLINE, EMBASE and International Pharmaceutical Abstracts databases, the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD group Specialized Trials Register.


METHODS
Randomized, double-blind, placebo-controlled trials of oral azathioprine or 6-mercaptopurine involving adult patients (> 18 years) with quiescent Crohn's disease.


METHODS
Data were extracted by three independent observers (EP, MC, LRS) based on the intention to treat principle. Peto odds ratios and 95% confidence intervals for maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined.


RESULTS
Seven trials of azathioprine therapy and one of 6-mercaptopurine were included in the review. Azathioprine and 6-mercaptopurine had a positive effect on maintaining remission. The Peto odds ratio (OR) for maintenance of remission with azathioprine was 2.32 (95% CI 1.55 to 3.49) with a NNT of 6. The Peto OR for maintenance of remission with 6-mercaptopurine was 3.32 (95% CI 1.40 to 7.87) with a of 4. Higher doses of azathioprine improved response. A steroid sparing effect with azathioprine was noted, with a Peto OR of 5.22 (95% CI 1.06 to 25.68) and NNT of 3 for quiescent disease. Withdrawals due to adverse events were more common in patients treated with azathioprine (Peto OR 3.74; 95% CI 1.48 to 9.45, NNH = 20) than with placebo.


CONCLUSIONS
Azathioprine and 6-mercaptopurine are more effective than placebo for maintenance of remission in Crohn's disease. Higher response rates were obtained with azathioprine than 6-mercaptopurine. However, the one study evaluating 6-mercaptopurine used a relatively low dose of the drug. Future studies should look at the effect of higher doses of 6-mercaptopurine. There is weak evidence for a steroid sparing effect with azathioprine treatment.
Prefontaine
Eliza
E
Department of Community Health Sciences, University of Calgary, Health Sciences Centre, 3330 Hospital Dr NW, Calgary, Alberta, Canada, T2N 4N1.
Sutherland
Lloyd R
LR
Macdonald
John K
JK
Cepoiu
Monica
M
D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015122:Mercaptopurine / Q000627:therapeutic use; D011355:Prodrugs / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction
D007166:Immunosuppressive Agents; D011355:Prodrugs; D015122:Mercaptopurine; D001379:Azathioprine