title: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial.
abstract: BACKGROUND
  Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab.
  
  
  METHODS
  We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710.
  
  
  RESULTS
  Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60.0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35.9%) of 64 controls, for an absolute difference of 24.1% (95% CI 7.3-40.8, p=0.0062). Corresponding rates at week 52 were 40/65 (61.5%) and 27/64 (42.2%) (absolute difference 19.3%, 95% CI 2.4-36.3, p=0.0278). 20 of the 65 patients (30.8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25.3%) controls (p=1.0).
  
  
  CONCLUSIONS
  Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.
authors.affiliation: Imelda Gastrointestinal Clinical Research Centre, Bonheiden, Belgium. Electronic address: geert.dhaens@imelda.be.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: H Hart Ziekenhuis, Roeselare, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Baert
authors.affiliation: University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: van Assche
authors.affiliation: Ziekenhuis Oost-Limburg, Genk, Belgium.
authors.forename: Philip
authors.initials: P
authors.lastname: Caenepeel
authors.affiliation: Groeninge Ziekenhuis, Kortrijk, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vergauwe
authors.affiliation: Medisch Centrum Alkmaar, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Tuynman
authors.affiliation: University Hospital, Gent, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: De Vos
authors.affiliation: Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: van Deventer
authors.affiliation: Department of Epidemiology and Biostatistics, University of Western Ontario, Canada.
authors.forename: Larry
authors.initials: L
authors.lastname: Stitt
authors.affiliation: Department of Epidemiology and Biostatistics, University of Western Ontario, Canada; Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Donner
authors.affiliation: University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Algemeen Ziekenhuis St Augustinus, Wilrijk, Belgium.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Van De Mierop
authors.affiliation: Clinique St Pierre, Ottignies, Belgium.
authors.forename: Jean-Charles R
authors.initials: JR
authors.lastname: Coche
authors.affiliation: Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: van der Woude
authors.affiliation: Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ochsenkühn
authors.affiliation: VU University Medical Centre Amsterdam, The Netherlands.
authors.forename: Ad A
authors.initials: AA
authors.lastname: van Bodegraven
authors.affiliation: Algemeen Ziekenhuis St Lucas, Brugge, Belgium.
authors.forename: Philippe P
authors.initials: PP
authors.lastname: Van Hootegem
authors.affiliation: Algemeen Ziekenhuis Damiaan Campus St Jozef, Oostende, Belgium.
authors.forename: Guy L
authors.initials: GL
authors.lastname: Lambrecht
authors.affiliation: Academisch Ziekenhuis VUB, Jette, Belgium.
authors.forename: Fazia
authors.initials: F
authors.lastname: Mana
authors.affiliation: University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Department of Epidemiology and Biostatistics, University of Western Ontario, Canada; Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hommes
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D001530:Belgium; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D005858:Germany; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D009426:Netherlands; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D000069285:Infliximab; D001379:Azathioprine; D008727:Methotrexate