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Background  Unlike perianal fistula, long‐term outcomes of nonperianal fistulae (NPF) in Crohn's disease (CD) are not clear. We aimed to compare the outcomes of medical and surgical therapies in patients with NPF.    Methods  We retrospectively analyzed the records of patients of CD with NPF who were prospectively followed from January 2005 to December 2018.    Results  Of the 53 patients with NPF [mean age at presentation:29 ± 14 years; 54.7% male; median duration of follow‐up: 47 months (interquartile range [IQR]:26–76 months)], enteroenteric fistula (37.8%) was the most common presentation. Of 22 patients treated with anti‐tumor necrosis factor (TNF) therapy, complete response was achieved in 40.9% ( n  = 9). Overall probability of maintaining response was similar between the anti‐TNF and surgical groups (95.2%  vs  82.4%; 71%  vs  76%; and 63%  vs  69%% [ P  = 0.8] at 1, 2, and 3 years, respectively), with only 13.6% of patients treated with biologicals requiring surgery over 56 months. Twenty‐one patients required upfront surgery (small bowel or ileocolonic resection with/without diversion; 28.5% emergent), with 47.6% postoperative recurrence over 36 months, of which nine patients required biologicals (77.7% response to anti‐TNF therapy). Long‐term outcome was comparable between medically and surgically treated patients; 6.4% developed tuberculosis on anti‐TNF therapy. Two patients (3.7%) developed malignancy (one ‐ enteroenteric, one ‐ colovesical).    Conclusion  Anti‐TNF therapy appears to be as effective as surgery in this retrospective analysis of patients with NPFCD, and it may be indicated in the absence of abscess and other complications. These patients are at higher risk of fistula‐associated malignancy, which requires a lower threshold for suspicion, especially over the long term in the presence of nonresponse to medical therapy.

Long‐term outcomes of anti‐tumor necrosis factor therapy and surgery in nonperianal fistulizing Crohn's disease