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Relapse rate following azathioprine withdrawal in maintaining remission for crohn's disease: a systematic review and meta-analysis
  1. H French,
  2. A M Dalzell,
  3. R Srinivasan,
  4. W El-Matary
  1. Division of Paediatric Gastroenterology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK


Aim The duration of using azathioprine (AZA) and 6-mercaptopurine (6-MP) for maintaining remission in Crohn's is debatable. The aim of this systematic review and meta-analysis was to examine whether Aza/6-MP can be safely withdrawn in patients with Crohn's disease who have been in remission.

Methods The following databases were searched: MEDLINE (1950- September 2010), EMBASE (1980- September 2010), CINHAL (1981- September 2010), PubMed (1950- September 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL). Randomised controlled and cohort studies comparing AZA continuation versus placebo or no treatment were eligible for inclusion. Primary outcomes were relapse rate following discontinuation of AZA/6-MP at 6, 12, 18 months, 5 years and 10 years. Secondary outcome was any reported side effects.

Results Five studies met the inclusion criteria with 256 patients and 168 controls. Stopping AZA/6-MP was found to significantly increase the risk of relapse at 6, 12 and 18 months with pooled OR of 0.22 (95% CI 0.09 to 0.53), 0.25 (95% CI 0.11 to 0.56) and 0.35 (95% CI 0.21 to 0.6) respectively. Two trials examined relapse rate at 5 years with pooled OR 0.53 (95% CI 0.13 to 2.21). No trials looking at relapse rates beyond 5 years were identified. Side effects reported in all studies were documented, showing serious but rare side effects in the Aza/6-MP group.

Conclusions There is a clear benefit of continuing Aza/6-MP for at least 18 months to maintain remission for Crohn's disease patients who established remission. There is no enough evidence to provide a clear guidance on whether to continue Aza/6-MP treatment or not beyond 18 months. Well-designed randomised controlled trials addressing this issue are needed.

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