Systematic versus Endoscopy-driven Treatment with Azathioprine to Prevent Postoperative Ileal Crohn's Disease Recurrence.
OBJECTIVE
Prophylactic azathioprine (AZA) is efficacious in preventing postoperative Crohn's disease (CD) recurrence. However, it is unknown whether AZA should be started immediately after surgery. We compared the efficacy of systematic vs endoscopy-driven AZA in preventing CD recurrence at week 102.


METHODS
This prospective, multicentre trial included CD patients undergoing curative resection with ileocolonic anastomosis and at higher risk of recurrence. Patients were randomized to systematic AZA initiated ≤2 weeks from surgery, or endoscopy-driven AZA in which therapy was only initiated in case of endoscopic recurrence (Rutgeerts' score ≥i2) at weeks 26 or 52 following surgery. The primary endpoint was endoscopic remission (i0-i1) at week 102. Secondary endpoints included complete endoscopic remission (i0) and clinical remission.


RESULTS
The study was prematurely stopped due to slow recruitment. Between 2005 and 2011, 63 patients (28 male, median age 36 years) were randomized to systematic (n = 32) or endoscopy-driven AZA (n = 31). Twenty-one patients withdrew prematurely (8 clinical recurrence, 6 adverse reactions to AZA, 7 patient's preference). In the endoscopy-driven AZA group, 14 patients had to initiate AZA (11 at week 26, 3 at week 52). Endoscopic remission was achieved by 50% in the systematic and 42% in the endoscopy-driven AZA group (p = 0.521). No difference in secondary endpoints was found.


CONCLUSIONS
Systematic AZA therapy in patients at higher risk of postoperative CD recurrence is not superior to endoscopy-driven treatment. Early postoperative endoscopic evaluation between weeks 26 and 52 seems most appropriate to guide further therapy, but larger studies are warranted. (ClinicalTrials.gov NCT02247258.).
Department of Gastroenterology, University Hospitals Leuven, KU Leuven, Leuven, Belgium marc.ferrante@uzleuven.be.
Marc
M
Ferrante
1st Department of Gastroenterology, Evangelismos Hospital, Athens, Greece.
Konstantinos
K
Papamichael
Department of Gastroenterology, Univerzity Karlovy, Prague, Czech Republic.
Dana
D
Duricova
Department of Gastroenterology, Imeldaziekenhuis, Bonheiden, Belgium.
Geert
G
D'Haens
Department of Gastroenterology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Severine
S
Vermeire
1st Department of Gastroenterology, Evangelismos Hospital, Athens, Greece.
Emmanuel
E
Archavlis
Department of Gastroenterology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Paul
P
Rutgeerts
Department of Gastroenterology, Univerzity Karlovy, Prague, Czech Republic.
Martin
M
Bortlik
1st Department of Gastroenterology, Evangelismos Hospital, Athens, Greece.
Gerassimos
G
Mantzaris
Department of Gastroenterology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Gert
G
Van Assche
D000328:Adult; D000714:Anastomosis, Surgical; D001379:Azathioprine / Q000627:therapeutic use*; D000066491:Clinical Decision-Making; D003106:Colon / Q000601:surgery*; D003113:Colonoscopy; D003424:Crohn Disease / Q000175:diagnosis / Q000517:prevention & control* / Q000601:surgery; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D007082:Ileum / Q000601:surgery*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D060828:Induction Chemotherapy; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D001379:Azathioprine
Prevention; azathioprine; postoperative recurrence