title: Crohn's disease management after intestinal resection: a randomised trial.
abstract: BACKGROUND
  Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence.
  
  
  METHODS
  In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patient's study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560.
  
  
  RESULTS
  Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0.03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0.03). In the active care arm, of those with 6 months recurrence who stepped up treatment, 18 (38%) of 47 patients were in remission 12 months later; conversely, of those in remission at 6 months who did not change therapy recurrence occurred in 31 (41%) of 75 patients 12 months later. Smoking (odds ratio [OR] 2.4, 95% CI 1.2-4.8, p=0.02) and the presence of two or more clinical risk factors including smoking (OR 2.8, 95% CI 1.01-7.7, p=0.05) increased the risk of endoscopic recurrence. The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and standard care groups (100 [82%] of 122 vs 45 [87%] of 52; p=0.51) and (33 [27%] of 122 vs 18 [35%] of 52; p=0.36), respectively.
  
  
  CONCLUSIONS
  Treatment according to clinical risk of recurrence, with early colonoscopy and treatment step-up for recurrence, is better than conventional drug therapy alone for prevention of postoperative Crohn's disease recurrence. Selective immune suppression, adjusted for early recurrence, rather than routine use, leads to disease control in most patients. Clinical risk factors predict recurrence, but patients at low risk also need monitoring. Early remission does not preclude the need for ongoing monitoring.
  
  
  BACKGROUND
  AbbVie, Gutsy Group, Gandel Philanthropy, Angior Foundation, Crohn's Colitis Australia, and the National Health and Medical Research Council.
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Austin Health, University of Melbourne, Austin Academic Centre, Heidelberg, VIC, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: De Cruz
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Medicine, Imperial College London, London, UK. Electronic address: mkamm@unimelb.edu.au.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kamm
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Hamilton
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Ritchie
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Efrosinia O
authors.initials: EO
authors.lastname: Krejany
authors.affiliation: Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, VIC, Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gorelik
authors.affiliation: Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, VIC, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Lani
authors.initials: L
authors.lastname: Prideaux
authors.affiliation: Centre for Inflammatory Bowel Diseases, Fremantle Hospital and The University of Western Australia, Fremantle, WA, Australia.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Lawrance
authors.affiliation: Department of Gastroenterology and Hepatology, Royal Adelaide Hospital and University of Adelaide, Adelaide, SA, Australia.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Andrews
authors.affiliation: Department of Gastroenterology and Hepatology, Flinders Medical Centre and Flinders University, Adelaide, SA, Australia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Bampton
authors.affiliation: Department of Gastroenterology, Alfred Health and Monash University, Melbourne, VIC, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Gibson
authors.affiliation: Department of Gastroenterology, Alfred Health, Melbourne, VIC, Australia.
authors.forename: Miles
authors.initials: M
authors.lastname: Sparrow
authors.affiliation: Gastroenterology and Liver Services, Concord and Bankstown Hospitals and The University of New South Wales, Sydney, NSW, Australia.
authors.forename: Rupert W
authors.initials: RW
authors.lastname: Leong
authors.affiliation: Department of Gastroenterology, Mater Health Services, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Florin
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Gearry
authors.affiliation: QIMR Berghofer Medical Research Institute, University of Queensland School of Medicine, Inflammatory Bowel Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Graham
authors.initials: G
authors.lastname: Radford-Smith
authors.affiliation: Department of Colorectal Medicine and Genetics, and Department of Medicine, Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Finlay A
authors.initials: FA
authors.lastname: Macrae
authors.affiliation: Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Melbourne, VIC, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Debinski
authors.affiliation: AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Warwick
authors.initials: W
authors.lastname: Selby
authors.affiliation: Department of Gastroenterology, Western Hospital, Melbourne, VIC, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Kronborg
authors.affiliation: Department of Colorectal Surgery, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Johnston
authors.affiliation: Department of Colorectal Surgery, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Rodney
authors.initials: R
authors.lastname: Woods
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: P Ross
authors.initials: PR
authors.lastname: Elliott
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Bell
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Brown
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: William R
authors.initials: WR
authors.lastname: Connell
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Desmond
mesh_terms: D000068879:Adalimumab; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D001379:Azathioprine / Q000627:therapeutic use; D003113:Colonoscopy; D003424:Crohn Disease / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D008795:Metronidazole; D015122:Mercaptopurine; D000068879:Adalimumab; D001379:Azathioprine