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

Abstract

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 Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU

“…Nevertheless, no The American Journal of GASTROENTEROLOGY randomized placebo-controlled trial has directly evaluated the efficacy of biologic agents when stricturing or penetrating disease has already developed (6). In addition, surgical management should be also discussed with these patients, including aspects such as the risk of postoperative recurrence, the need for prophylactic therapy, and even further surgical interventions (18). Previous studies evaluating different types of fistulas and outcomes showed that anti-TNF agents may be effective in this setting (6,18), although this has been mostly in small case series and only in the short term (8,(19)(20)(21)(22)(23).…”

“…In addition, surgical management should be also discussed with these patients, including aspects such as the risk of postoperative recurrence, the need for prophylactic therapy, and even further surgical interventions (18). Previous studies evaluating different types of fistulas and outcomes showed that anti-TNF agents may be effective in this setting (6,18), although this has been mostly in small case series and only in the short term (8,(19)(20)(21)(22)(23). In a cohort of 93 patients with penetrating disease (77% entero-enteric or entero-colonic, 17% entero-vesical, and 5% entero-vaginal), 27% of patients achieved fistula closure after 5 years of follow-up, and 47% required surgery (10).…”

“…Nevertheless, no randomized placebo-controlled trial has directly evaluated the efficacy of biologic agents when stricturing or penetrating disease has already developed (6). In addition, surgical management should be also discussed with these patients, including aspects such as the risk of postoperative recurrence, the need for prophylactic therapy, and even further surgical interventions (18).…”

“…Previous studies evaluating different types of fistulas and outcomes showed that anti-TNF agents may be effective in this setting (6,18), although this has been mostly in small case series and only in the short term (8,19–23). In a cohort of 93 patients with penetrating disease (77% entero-enteric or entero-colonic, 17% entero-vesical, and 5% entero-vaginal), 27% of patients achieved fistula closure after 5 years of follow-up, and 47% required surgery (10).…”

Biomarkers in Inflammatory Bowel Diseases: Predicting the Indication and the Effect of Biologics

“…Regarding CD sub-phenotypes, patients with inflammatory phenotype (B1) respond better to infliximab [12], while patients with stricturing disease (B2) correlate with long term lack of response [142]. In patients with penetrating CD (B3), the response to anti-TNF depends on the type of fistulae; in patients with perianal fistulae both adalimumab and infliximab seem effective [23], with therapeutic drug monitoring levels being indicative of the response [143][144][145][146], while in patients with non-perianal fistulae, surgery seems to be unavoidable [147].…”