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).