Exabis Library

Current guidelines on Crohn’s perianal fistulas recommend anti-TNF treatment and suggest to consider surgical closure in amendable patients. However, long-term outcome of both treatments have not been directly compared. The aim of this study was to assess MRI healing in a patient preference RCT comparing both treatment modalities.

This multicentre, international trial compared surgical closure following anti-TNF induction (4 months) to anti-TNF therapy without surgery. Patients were counselled for both treatment arms and randomised if there was no preference. Due to the combination of a preference and randomised cohort, the appropriate sample size to detect a clinically relevant increase of 25% closure (from 15% to 40%) was flexible and adjusted for a possible skewed distribution (86 patients in case of 1:1 treatment allocation).

All Crohn’s patients ≥ 18 years with a (re)active high perianal fistula and a single internal opening were eligible. Exclusion criteria were previous failure of anti-TNF, recto-vaginal fistula, proctitis, or stoma. Patients received seton placement prior to treatment. Primary outcome was MRI healing after 18 months (defined as a complete fibrotic fistula or MAGNIFI-CD score of 0-5). Secondary outcomes included clinical healing, re-interventions and fistula recurrence.

Between September 2013 and December 2019, 7 hospitals in the Netherlands and Italy included 93 patients (59% females, median age 34 years) of which 32 were randomised. Thirty-seven patients were treated in the surgical closure group and 56 in the anti-TNF group, with comparable baseline characteristics.

After 18 months, MRI healing was significantly higher after surgical closure (41% vs 11%; P=0.002). Although a trend was seen in favour of surgical closure, clinical healing rates and surgical re-interventions were not significantly different between groups (65% vs 45%, P=0.07 and 19% vs 34%, P=0.1). After median 38 months follow-up, 12 patients in the anti-TNF group crossed over to surgical closure. Both long-term MRI healing and clinical closure in the per protocol analysis remained significantly higher for the surgical closure group (46% vs 11%, P=0.002 and 65% vs 29%, P=0.006). One patient (4%) with a MAGNIFI-CD score ≤5 developed a recurrent fistula after 46 months, whereas recurrences occurred in 37% of patients with MAGNIFI-CD score >5 (P=0.004).

These results demonstrate that surgical closure following anti-TNF induction treatment induces MRI healing more frequently than anti-TNF alone. This is associated with increased long-term clinical closure and reduced recurrences. These data suggest that Crohn’s perianal fistula patients amendable for surgical closure should be counselled for this therapeutic approach.

Limited resective surgery is used as a primary therapeutic option in patients with Crohn’s disease (CD) who present with severe symptoms or fibrostenotic complications. Recent studies suggest that surgery represents a valid alternative of biological therapy in subgroups of CD patients.¹ However, only few studies have described the disease course in early resected CD patients regardless of disease location. This study aimed to investigate disease course in all early resected CD patients.

Using the Danish National Patient Registry (NPR), we identified 9739 patients who were diagnosed with CD between January 1^st, 1997 and December 31^st, 2015. Of those, 499 patients underwent a major abdominal surgery within 30 days before or after their diagnosis. Data on re-operation, hospitalization and medication use were retrieved from the NPR and the National Prescription Registry. Trends in treatment outcomes over time were assessed using Chi-square test, Kaplan Meier survival analysis and log-rank test.

Overall, 217 (43.5%) patients had an initial ileocecal resection, 154 (30.9%) had a colonic resection and 112 (22.4%) had a small bowel resection and 16(3.2%) patients without classification of  surgery. The cumulative risk of reoperation was 16.4% at five years after the initial surgery. Five-year risk of hospitalization and need for medical therapy was 66.1% and 61.7% (Figure 1). Among 326 (65.3%) patients who received medical therapy during follow-up, 216 (66.3%) were treated with an immunomodulator and 62 (19.0%) with a biological drug. There was no difference in the risk of re-operation (p=0.11), hospitalization (p=0.70) or medication use (p=0.37) in relation to the anatomic location of the initial surgery.

When comparing patients diagnosed before and after 2005, five-year risk of hospitalization decreased from 76.9% to 56.1% (p<0.001, Figure 2), while five-year risk of medication use decreased from 65.9% to 58.5% (p=0.01, Figure 2). In contrast, five-year risk of re-operation showed an increasing, but insignificant trend from 13.7% to 18.6% (p=0.18).

Figure 1. Cumulative risk of re-operation, hospitalization and medication use

The risk of re-operation and hospitalization after the initial surgery in this cohort of early resected CD patients are lower when compared to other CD cohorts. Furthermore, hospitalization risk and need for medical therapy decreased over time.

¹.Stevens TW, Haasnoot ML, D’Haens GR, Buskens CJ, de Groof EJ, Eshuis EJ, et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn’s disease: retrospective long-term follow-up of the LIR!C trial. Lancet Gastroenterol Hepatol. 2020 Oct 1;5(10):900–7.