OP18 Treatment of perianal fistulas in Crohn’s Disease: Surgical closure after anti-TNF induction treatment versus anti-TNF without surgery (PISA II) - A patient preference RCT
Meima - van Praag, E.(1);van Rijn, K.(2);Snijder, A.(3);Wasmann, K.(4);Stoker, J.(2);D'Haens, G.(3);Gecse, K.(3);Gerhards, M.(5);Jansen, J.(6);Pronk, A.(7);van Tyl, S.(8);Zimmerman, D.(9);Bruin, K.(10);Spinelli, A.(11);Danese, S.(12);van der Bilt, J.(13);Mundt, M.(14);Bemelman, W.(1);Buskens, C.(1)
(1)Amsterdam UMC, Surgery, Amsterdam, The Netherlands;(2)Amsterdam UMC, Radiology and Nuclear Medicine, Amsterdam, The Netherlands;(3)Amsterdam UMC, Gastroenterology and Hepatology, Amsterdam, The Netherlands;(4)Amsterdam UMC, Surgery, Amsterda-, The Netherlands;(5)OLVG, Surgery, Amsterdam, The Netherlands;(6)OLVG, Gastroenterology and Hepatology, Amsterdam, The Netherlands;(7)Diakonessenhuis, Surgery, Utrecht, The Netherlands;(8)Diakonessenhuis, Gastroenterology and Hepatology, Utrecht, The Netherlands;(9)Elisabeth-TweeSteden Hospital, Surgery, Tilburg, The Netherlands;(10)Elisabeth-TweeSteden Hospital, Gastroenterology and Hepatology, Tilburg, The Netherlands;(11)Humanitas Research Hospital and Humanitas University, Surgery, Milan, Italy;(12)Humanitas Research Hospital and Humanitas University, Gastroenterology, Milan, Italy;(13)Flevoziekenhuis, Surgery, Almere, The Netherlands;(14)Flevoziekenhuis, Gastroenterology and Hepatology, Almere, The Netherlands
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.