Biologics & internal fistulizing CD

July 18, 2023

Issue 14

Clinical Question

How effectively do biologics treat internal fistulas in Crohn’s disease?

Editor’s Bottom Line

Very few data have been reported to describe the outcomes of internal fistulas in patients with Crohn’s disease. In this large cohort, rates of surgery remained high despite use of biologic therapy.

Reference

Barreiro-de Acosta M, Fernández-Clotet A, Mesonero F, et al. Long-Term Outcomes of Biological Therapy in Crohn’s Disease Complicated with Internal Fistulizing Disease: BIOSCOPE Study From GETECCU. Am J Gastroenterol. 2023;118(6):1036–46; https://journals.lww.com/ajg/Fulltext/2023.aspx

Synopsis

To document the impact of biologic agents on the trajectory of internal fistulas in Crohn’s disease (CD), researchers studied 760 adults with CD-related fistulae included in the ENEIDA registry, a prospectively maintained database supported by the Spanish Working Group on Crohn’s disease and ulcerative Colitis (GETECCU).

Patients had been treated at 53 hospitals in Spain and received one or more biologics, most commonly anti-tumor necrosis factor (TNF) agents. The most common fistula types were entero-enteric, entero-colic, sinus and entero-urinary, while colo-colic, entero-uterine and entero-duodenal fistulas were less common. Between 15% and 20% of patients in each medication group had an abscess at baseline, and 37–45% had a stricture distal to the fistula. Median follow-up was 56 months (Interquartile Range [IQR]: 26–102 months).

Results showed that 32% of patients required surgery due to intra-abdominal fistulizing complications within a median of eight months (IQR: 3–23 months). Rates of surgery for recipients of anti-TNF agents, vedolizumab, or ustekinumab were not significantly different, with 32%, 41%, and 24% of patients in these groups, respectively, requiring surgery.

In multivariate analyses, the specific biologic used did not affect the risk of surgery. Older age (Hazard Ratio [HR]: 1.03; 95% Confidence Interval [CI]: 1.02–1.05; p=0.001), ileocolonic disease (HR: 2.72; 95% CI, 1.12–6.59; p=0.03), entero-urinary fistulae (HR: 2.22; 95% CI, 1.13–4.37; p=0.02) and intestinal strictures distal to the origin of the fistula (HR: 1.92; 95% CI, 1.25–2.96; (p=0.003) predicted a higher risk of surgery, while not smoking (HR: 0.49; 95% CI, 0.31–0.79; p=0.003) and receiving combination therapy with an immunomodulator (HR: 0.65; 95% CI, 0.45–0.93; p=0.02) were associated with a lower risk of surgery.

Biologic treatment led to fistula closure in 24% of patients after a median 15 months of therapy [IQR: 7–25 months]. Predictors of closure included fewer fistulous tracts (HR: 1.72; 95% CI, 1.09–2.7; p=0.02), abscess at baseline (HR: 1.79; 95% CI, 1.05–3.05; p=0.03), older age (HR: 1.02; 95% CI, 1.01–10.4; p=0.004), and not smoking (HR: 2.09; 95% CI, 1.14–3.86; p=0.02). Females (HR: 0.56; 95%, 0.35–0.91; p=0.02) and those with colonic disease (HR: 0.51; 95% CI, 0.33–0.80; p=0.003) were less likely to experience fistula closure with treatment.

Safety analysis showed that 13% of infliximab recipients developed an adverse event, compared to 8%, 0% and 0% with adalimumab, vedolizumab and ustekinumab, respectively (p=0.001 for infliximab vs. others).

Details

Study Design: Retrospective national cohort

Funding: The ENEIDA registry is supported by Biogen, Pfizer and Takeda.

Allocation: Not applicable

Setting: Multicenter

Level of Evidence: 2b