Relapse Rate Following Azathioprine Withdrawal in Maintaining Remission for Crohn's Disease: A Meta-Analysis

The duration of use of azathioprine (Aza) and 6-mercaptopurine (6-MP) for maintaining remission for Crohn's disease is debatable. To examine whether Aza/6-MP can be safely withdrawn in patients with Crohn's disease who have been in remission. 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 azathioprine continuation versus placebo or no treatment were eligible for inclusion. Primary outcomes were relapse rate after discontinuation of Aza/6-MP at 6, 12, and 18 months, and 5 and 10 years. Five studies, with 256 patients and 168 controls, met the inclusion criteria. Stopping azathioprine/6-MP was found to significantly increase the risk of relapse at 6, 12, and 18 months with pooled odds ratios of 0.22 (95% CI 0.09-0.53), 0.25 (95% CI 0.11-0.56), and 0.35 (95% CI 0.21-0.6), respectively. Two trials examined relapse rate at 5 years with pooled OR 0.53 (95% CI 0.13-2.21). No trials looking at relapse rates beyond 5 years were identified. 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 not enough evidence to provide clear guidance on whether or not to continue Aza/6-MP treatment beyond 18 months. Well-designed randomised controlled trials addressing this issue are needed.