Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn's disease: A controlled randomized trial

Background & Aims: More than 80% of Crohn's disease (CD) patients undergoing resection suffer recurrence of their disease. Therapy with aminosalicylates, antimetabolites, or antibiotics leads to a modest reduction in the incidence of recurrence. Goal. We sought to examine whether metronidazole for 3 months together with azathioprine (AZA) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in "high-risk" patients. Methods: CD patients undergoing curative ileocecal resection with >= 1 risk factor for recurrence received metronidazole (3 months) and AZA/placebo (12 months). The primary end point was the proportion of patients with significant endoscopic recurrence 3 and 12 months after surgery. Secondary end points included clinical recurrence, safety, and tolerability of treatment. Results: Eighty-one patients were randomized; 19 discontinued the study early. Significant endoscopic recurrence was observed in 14 of 32 (43.7%) patients in the AZA group and in 20 of 29 (69.0%) patients in the placebo group at 12 months postsurgery (P = .048). Intention-to-treat analysis revealed endoscopic recurrence in 22 of 40 (55%) in the AZA group and 32 of 41 (78%) in the placebo group at month 12 (P = .035). At month 12, 7 of 32 patients had no endoscopic lesions in the AZA group, versus I of 29 in the placebo group (P = .037). Conclusions: Despite the enhanced risk of recurrence, the overall incidence of significant recurrence was rather low, probably owing to the metronidazole treatment that all patients received. Concomitant AZA resulted in lower endoscopic recurrence rates and less severe recurrences 12 months postsurgery, predicting a more favorable clinical outcome. This combined treatment seems to be recommendable to all operated CD patients with an enhanced risk for recurrence.