Reply to Dr. Kotze's and Dr. Yamamoto's letter.

We appreciate the opportunity to reply to Dr. Kotze's and Dr. Yamamoto's letter1 about our paper “Prevention of postoperative recurrence with azathioprine or infliximab in patients with Crohn's disease: an open-label pilot study”, recently accepted for publication in JCC.2 We agree with the first comment concerning the hypothesis that the use of anti-TNF (tumor necrosis factor)-α before surgery could control disease activity in the long term. This remains only a hypothesis, however, since no formal study has focused on this issue so far, in particular more than one year after anti-TNFα discontinuation. Also in the study by Regueiro et al.3, 5 of 13 patients treated with placebo have been previously treated with infliximab and rates of endoscopic recurrence in that group was high (84.6%). In our study, the presence of active perianal disease at time of surgery was an exclusion criteria. The evaluation of perianal fistulas was only clinical at enrollment, as in most of the trials evaluating medical treatment in perianal disease. However, all patients with history of perianal disease included in our study also had the most recent pelvic radiological examination negative for active disease. We agree with Dr. Kotze and Dr. Yamamoto1 about the very interesting possibility to plan a study focused on medical prevention of radiological recurrence in patients undergoing ileocecal resection, considering that Crohn's disease (CD) has a transmural involvement. However, the gold standard for the definition of postoperative recurrence is currently based on endoscopic findings and this is why the primary outcome in our study was the prevention of endoscopic recurrence.4 We also agree about the need of larger studies to find the better treatment for the prevention of postoperative recurrence in CD. Twenty-two patients are few, but our study represents the first direct comparison between azathioprine and infliximab, and may be considered as an incentive to extend this evaluation to a greater number of patients. Subjects pre-operatively treated with biological therapy could represent a “high risk” subpopulation for postoperative recurrence, supposing that their disease activity could be more aggressive to justify the indication to start anti-TNFα in comparison with those receiving only conventional treatments.