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Intervention Review

Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease

  1. Eliza Prefontaine1,
  2. John K MacDonald2,
  3. Lloyd R Sutherland1,*

Editorial Group: Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group

Published Online: 7 OCT 2009

Assessed as up-to-date: 30 JUL 2009

DOI: 10.1002/14651858.CD000545.pub2


How to Cite

Prefontaine E, MacDonald JK, Sutherland LR. Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD000545. DOI: 10.1002/14651858.CD000545.pub2.

Author Information

  1. 1

    University of Calgary, Department of Community Health Sciences, Calgary, Alberta, Canada

  2. 2

    Robarts Research Institute, Robarts Clinical Trials, London, Ontario, Canada

*Lloyd R Sutherland, Department of Community Health Sciences, University of Calgary, Health Sciences Centre, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4N1, Canada. lsutherl@ucalgary.ca. lloyd.sutherland@shaw.ca.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 7 OCT 2009

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This is not the most recent version of the article. View current version (30 APR 2013)

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

Background

The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease were conflicting and controversial. A meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease.

Objectives

To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease.

Search strategy

Studies were selected using the MEDLINE database (1966 to July 2009), abstracts from major gastrointestinal meetings and references from published articles and review. The Cochrane Trials Register and the Inflammatory Bowel Disease Review Group Trials Register were also searched. This search strategy was updated using the MEDLINE, EMBASE and the International Pharmaceutical Abstracts databases as well as the Cochrane Register of Controlled Trials and the Cochrane IBD/FBD group Specialized Trials Register.

Selection criteria

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

Data collection and analysis

Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel.

Main results

Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms. The odds ratio (OR) of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.43 (95% CI 1.62 to 3.64). This corresponded to a number needed to treat (NNT) of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the OR was 2.06 (95% CI 1.25 to 3.39). Treatment > 17 weeks increased the OR to 2.61 (95% CI 1.69 to 4.03). A steroid sparing effect was seen with an OR of 3.69 (95% CI 2.12 - 6.42), corresponding to a NNTof about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased with active therapy with an odds ratio of 3.44 (95% CI 1.52 to 7.77). The NNT to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14.

Authors' conclusions

Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. The OR of response increases after > 17 weeks of therapy, suggesting that there is a minimum length of time for a trial of azathioprine or 6-mercaptopurine therapy. Adverse events were more common among patients on active therapy.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Azathioprine or 6-mercaptopurine for the treatment of active Crohn's disease

Azathioprine and 6-mercaptopurine may be effective for inducing remission in Crohn's disease among patients with chronically active disease. These drugs may reduce the need for steroid treatment and their use may therefore lead to a lower incidence of steroid related side effects. However, these drugs are slow acting and are associated with some rare, but serious side effects. In some patients they suppress formation of blood cells that fight off infection and allow blood to clot and they occasionally cause inflammation of the pancreas. These drugs have also been associated with an increased risk of lymphoma. For these reasons careful consideration needs to be given to the use of these drugs as the primary treatment for patients experiencing an acute flare of Crohn's disease.