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Lancet. 2008 Feb 23;371(9613):660-667. doi: 10.1016/S0140-6736(08)60304-9.

Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial.

Author information

1
Imelda Gastrointestinal Clinical Research Centre, Bonheiden, Belgium. Electronic address: geert.dhaens@imelda.be.
2
H Hart Ziekenhuis, Roeselare, Belgium.
3
University Hospital Gasthuisberg, Leuven, Belgium.
4
Ziekenhuis Oost-Limburg, Genk, Belgium.
5
Groeninge Ziekenhuis, Kortrijk, Belgium.
6
Medisch Centrum Alkmaar, The Netherlands.
7
University Hospital, Gent, Belgium.
8
Academic Medical Centre, Amsterdam, The Netherlands.
9
Department of Epidemiology and Biostatistics, University of Western Ontario, Canada.
10
Department of Epidemiology and Biostatistics, University of Western Ontario, Canada; Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada.
11
Algemeen Ziekenhuis St Augustinus, Wilrijk, Belgium.
12
Clinique St Pierre, Ottignies, Belgium.
13
Erasmus University Medical Centre, Rotterdam, The Netherlands.
14
Ludwig-Maximilians Universität, Munich, Germany.
15
VU University Medical Centre Amsterdam, The Netherlands.
16
Algemeen Ziekenhuis St Lucas, Brugge, Belgium.
17
Algemeen Ziekenhuis Damiaan Campus St Jozef, Oostende, Belgium.
18
Academisch Ziekenhuis VUB, Jette, Belgium.
19
Leiden University Medical Centre, Leiden, Netherlands.

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.

FINDINGS:

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).

INTERPRETATION:

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.

PMID:
18295023
DOI:
10.1016/S0140-6736(08)60304-9
[Indexed for MEDLINE]

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