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

Abstract

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.

Immediate prophylactic vs endoscopic or symptomatic‐driven azathioprine treatment to prevent surgical recurrence after intestinal resection for Crohn's disease

“…In one study, mesalazine had a modest effect in preventing postoperative clinical recurrence compared with placebo, but its benefit on surgical recurrence was unclear . Meta‐analyses confirmed that thiopurines could reduce the risk of postoperative clinical and endoscopic recurrence compared with placebo or mesalazine . Although several studies reported that postoperative thiopurines were associated with a lower rate of surgical recurrence, a large RCT failed to detect any difference between mercaptopurine and placebo .…”

Management of postoperative Crohn’s disease

“…The efficacy of purine analogs was superior to that of placebo for the prevention of clinical (mean differences: 13%; 95% CI: 1.8-25%; NNT: 7) and endoscopic (mean differences: 23%; 95% CI: 9-37%; NNT: 4) recurrence at 1 year [47]. Purine analogs were more efficacious than 5-aminosalicylates in preventing endoscopic recurrence at 1 year (RR: 0.71; 95% CI: 0.53-0.94), but there was no significant difference in clinical recurrence between the groups (RR: 0.88; 95% CI: 0.60-1.30) [63]. Both meta-analyses found that compared to placebo (p = 0.021) or 5-aminosalicylates (p = 0.001), purine analogs were associated with a higher rate of adverse events leading to dropout.…”

“…Two meta-analyses compared purine analogs (azathioprine/ 6-mercaptopurine) with placebo or 5-aminosalicylates for the prevention of postoperative recurrence in CD [47,63]. The efficacy of purine analogs was superior to that of placebo for the prevention of clinical (mean differences: 13%; 95% CI: 1.8-25%; NNT: 7) and endoscopic (mean differences: 23%; 95% CI: 9-37%; NNT: 4) recurrence at 1 year [47].…”

Optimal delivery of follow-up care after surgery for Crohn’s disease: current perspectives

“… 36 – 38 In a meta-analysis of studies comparing thiopurines to mesalamine, both were equally effective at maintaining clinical remission; however, thiopurines were more effective at reducing endoscopic recurrence for the first year (RR =0.71). 39 However, in a randomized trial, 22% of participants had to stop thiopurines due to side effects or medication intolerance. 40 In a network meta-analysis, thiopurines were associated with reduced clinical (RR =0.36; 95% CI =0.17–0.63) and endoscopic (RR =0.33; 95% CI =0.13–0.68) recurrence.…”