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Abstract

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  2. Abstract
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Reinisch W, Angelberger S, Petritsch W, et al. Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomized, double-blind, double-dummy, multicentre trial. (Inflamm Bowel Dis 2011;)

Reinisch W, Angelberger S, Petritsch W, et al. Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomized, double-blind, double-dummy, multicentre trial. Gut. 2010;59:752–759.

Crohn's disease (CD) recurs in nearly half of patients within 5 years of surgical resection. The therapeutic options for prevention of postoperative recurrence are limited. A meta-analysis of 15 trials showed that mesalazine significantly reduces the risk of symptomatic recurrence.1 Data concerning the use of azathioprine has been more limited. Early postoperative endoscopic recurrence has been shown to predict the risk of subsequent clinical recurrence. No randomized study has compared the use of azathioprine and mesalazine in preventing clinical recurrence in high-risk postoperative patients (those shown to have early endoscopic recurrence).

Reinisch et al conducted a 52-week, double-blind, double-dummy, randomized trial of azathioprine versus mesalazine. CD patients who had 1) undergone ileocolonic resection with construction of an anastamosis in the preceding 6–24 months, 2) not experienced clinical recurrence postoperatively, and 3) a Crohn's Disease Activity Index (CDAI) score of <200 had screening colonoscopy performed. In all, 78 patients with moderate (Rutgeerts grade i2a: >5 aphthous lesions with normal mucosa between the lesions, or skip areas of larger lesions) to severe (Rutgeerts grade i3/4; diffuse aphthous ileitis with diffusely inflamed mucosa, or diffuse inflammation with larger ulcers, nodules, and/or narrowing) endoscopic recurrence were enrolled. Patients were randomized to receive azathioprine 2–2.5 mg/kg/day or mesalazine 4 g/day. Therapeutic failure occurred in 22% of patients receiving azathioprine (9/41) and 10.8% of patients in the mesalazine group (4/37) (P = 0.19). A subset analysis, however, revealed that all therapeutic failures in the azathioprine group were due to discontinuation secondary to adverse drug reactions (including six cases of pancreatitis) (P = 0.002), whereas four of the mesalazine patients developed clinical recurrence due to presumed lack of efficacy (P = 0.031). Follow-up colonoscopies were performed on subjects at month 12 or at the time of study withdrawal (varying from 3–12 months). The proportion of patients showing a ≥1 point reduction in the Rutgeert score was 63.3% in the azathioprine group and 34.4% in the mesalazine group, a difference of 28.9% (P = 0.023).

COMMENT

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  2. Abstract
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Given the high rate of recurrence in CD patients postresection, various strategies for which medications to choose and which patients to use them in have been employed. Proposed medical strategies have included 5-aminosalicylate (5-ASA), azathioprine, or 6-mercaptopurine (6-MP), antibiotics, and most recently infliximab. Confounding the various medical choices has been the absence of a single prognostic marker to predict those patients at highest risk for recurrence. Endoscopic recurrence appears to be the best single predictor of clinical recurrence.2, 3. Two out of three comparative trials of azathioprine versus mesalazine have shown lower rates of endoscopic recurrence with azathioprine.4, 5 This study does add some compelling evidence that patients with the highest risk of clinical recurrence (as predicted in the study by endoscopic recurrence) have better outcomes with azathioprine versus mesalazine, although notably the side effect profile of azathioprine represents a major limitation.

Although this data provides some evidence for azathioprine or mesalazine, it also raises several questions. When should we be performing the first postoperative endoscopy on our patients? Should we reserve treatment until endoscopic recurrence is documented? Additionally, placebo-controlled trials with infliximab postoperatively have recently been published and shown positive results.6 This may eventually change the approach to postoperative treatment. Given the multitude of factors which must be incorporated into postoperative management, it is likely that a standard of care is not yet on the horizon. However, we should use new information such as this to continue to expand our paradigm.

REFERENCES

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  2. Abstract
  3. COMMENT
  4. REFERENCES