Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn's disease : a meta-analysis

OBJECTIVES: To evaluate the efficacy and safety of purine analogs (azathioprine, 6-mercaptopurine (6-MP)) in the prevention of postoperative recurrence in Crohn's disease (CD).METHODS:We searched MEDLINE, the Cochrane Library, and EMBASE. The primary end points, clinical and endoscopic recurrence at 1 and 2 years, and safety were analyzed by the methods of Peto and Der Simonian and Laird.RESULTS:Four controlled trials enrolled 433 patients and compared azathioprine (n3) or (6-MP) (n1) with control arms (placebo with or without antibiotic induction therapy or mesalamine). In the overall analysis, purine analogs were more effective than control arms in preventing clinical recurrence at 1 year (mean difference, 95% confidence interval (CI): 8, 1-15%, P0.021, number needed to treat (NNT)13) and 2 years (mean difference, 95% CI: 13%, 2-24%, P0.018, NNT8). In sensitivity analyses, the efficacy of purine analogs was superior to that of placebo for the prevention of clinical and endoscopic recurrence at 1 year (mean differences, 95% CI: 13, 1.8-25%, P0.025, NNT7, and 23%, 9-37%, P0.0016, NNT4, respectively). At 1 year, in the overall analysis, purine analogs were more effective than control arms were in preventing severe (i2-4) endoscopic recurrence (mean difference, CI 95%: 15, 1.8-29%, P0.026, NNT7), but they were not effective in the prevention of very severe (i3-4) recurrence. The rate of adverse events leading to drug withdrawal was higher in thiopurine-treated patients than in control arms (17.2 vs. 9.8%, respectively, P0.021).CONCLUSIONS:Purine analogs are more effective than placebo in preventing both clinical and endoscopic postoperative recurrence in CD, but they are associated with a higher rate of adverse events leading to drug withdrawal.