Purine analogues compared with mesalamine or 5-ASA for the prevention of postoperative recurrence in Crohn's disease: a meta-analysis

Objective: To use a meta-analysis approach to evaluate the efficacy and safety of purine analogues, azathioprine (AZA) and 6-mercaptopurine (6-MP), in the prevention of postoperative recurrence of Crohn's disease (CD), as compared with mesalamine or 5-aminosalicylic acid (5-ASA). Methods: The Pubmed, Cochrane Library, and Embase literature databases were searched for relevant studies with the key words "azathioprine", "6-mercaptopurine", "purine analogue", "mesalamine", or "5-ASA". The efficacy and safety of purine analogues in the retrieved randomized controlled trials (RCTs) were evaluated with RevMan 5.0.25 (The Cochrane Collaboration, Oxford, England) and STATA 12.0 (Stata Corporation, College Station, TX, USA). The outcome measures of AZA and 6-MP, compared to mesalamine and 5-ASA (control arms), were: clinical recurrence, endoscopic recurrence, and adverse event rates. Results: Five RCTs, comprised of 429 patients, were analyzed. The effect of purine analogues for preventing clinical recurrence for year 1 and 2 were similar to controls (year 1: n = 390; recurrence rate: 18.6% vs. 20.9%; RR: 0.88, 95% CI: 0.60-1.30, p = 0.53; year 2: n = 270; recurrence rate: 29.9% vs. 38.2%; RR: 0.76, 95% CI: 0.55-1.05, p = 0.10). In contrast, purine analogues were more effective than controls in preventing severe endoscopic recurrence (i2-4) for year 1 (n = 289; 32.4% vs. 46.1%; RR: 0.71, 95% CI: 0.53-0.94, p = 0.02). However, purine analogues were associated with more adverse events leading to drug withdrawal than the controls (20.1% vs. 7.9%; RR: 2.57, 95% CI: 1.47-4.51, p = 0.0010). Conclusion: Purine analogues are more effective than controls in preventing endoscopic postoperative recurrence in CD, but are associated with more adverse events.