Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial.
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.
D'Haens
Geert
G
Imelda Gastrointestinal Clinical Research Centre, Bonheiden, Belgium. Electronic address: geert.dhaens@imelda.be.
Baert
Filip
F
H Hart Ziekenhuis, Roeselare, Belgium.
van Assche
Gert
G
University Hospital Gasthuisberg, Leuven, Belgium.
Caenepeel
Philip
P
Ziekenhuis Oost-Limburg, Genk, Belgium.
Vergauwe
Philippe
P
Groeninge Ziekenhuis, Kortrijk, Belgium.
Tuynman
Hans
H
Medisch Centrum Alkmaar, The Netherlands.
De Vos
Martine
M
University Hospital, Gent, Belgium.
van Deventer
Sander
S
Academic Medical Centre, Amsterdam, The Netherlands.
Stitt
Larry
L
Department of Epidemiology and Biostatistics, University of Western Ontario, Canada.
Donner
Allan
A
Department of Epidemiology and Biostatistics, University of Western Ontario, Canada; Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada.
Vermeire
Severine
S
University Hospital Gasthuisberg, Leuven, Belgium.
Van De Mierop
Frank J
FJ
Algemeen Ziekenhuis St Augustinus, Wilrijk, Belgium.
Coche
Jean-Charles R
JR
Clinique St Pierre, Ottignies, Belgium.
van der Woude
Janneke
J
Erasmus University Medical Centre, Rotterdam, The Netherlands.
Ochsenkühn
Thomas
T
Ludwig-Maximilians Universität, Munich, Germany.
van Bodegraven
Ad A
AA
VU University Medical Centre Amsterdam, The Netherlands.
Van Hootegem
Philippe P
PP
Algemeen Ziekenhuis St Lucas, Brugge, Belgium.
Lambrecht
Guy L
GL
Algemeen Ziekenhuis Damiaan Campus St Jozef, Oostende, Belgium.
Mana
Fazia
F
Academisch Ziekenhuis VUB, Jette, Belgium.
Rutgeerts
Paul
P
University Hospital Gasthuisberg, Leuven, Belgium.
Feagan
Brian G
BG
Department of Epidemiology and Biostatistics, University of Western Ontario, Canada; Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada.
Hommes
Daniel
D
Leiden University Medical Centre, Leiden, Netherlands.
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
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D000069285:Infliximab; D001379:Azathioprine; D008727:Methotrexate