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

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doi:10.1016/S0140-6736(08)60304-9 Copyright © 2008 Elsevier Ltd All rights reserved.

Articles

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

Geert D'Haens MDa, , , Filip Baert MDb, Gert van Assche MDc, Philip Caenepeel MDd, Philippe Vergauwe MDe, Hans Tuynman MDf, e De Vos MDg, Sander van Deventer MDh, Larry Stitt MSci, Prof Allan Donner PhDi, j, Severine Vermeire MDc, J Van De Mierop MDk, Jean- R Coche MDl, Janneke van der Woude MDm, Ochsenkühn MDn, Ad A van Bodegraven MDo, Philippe P Van Hootegem MDp, Guy L Lambrecht MDq, Fazia Mana MDr, Prof Rutgeerts MDc, Prof G Feagan MDi, j, Hommes MDs, for the Belgian Inflammatory Bowel Disease Research Group and the North-Holland Gut Club aImelda Gastrointestinal Clinical Research Centre, Bonheiden, BelgiumbH Hart Ziekenhuis, Roeselare, BelgiumcUniversity Hospital Gasthuisberg, Leuven, BelgiumdZiekenhuis Oost-Limburg, Genk, BelgiumeGroeninge Ziekenhuis, Kortrijk, BelgiumfMedisch Centrum Alkmaar, The NetherlandsgUniversity Hospital, Gent, BelgiumhAcademic Medical Centre, Amsterdam, The NetherlandsiDepartment of Epidemiology and Biostatistics, University of Western Ontario, CanadajRobarts Clinical Trials, Robarts Research Institute, London, Ontario, CanadakAlgemeen Ziekenhuis St Augustinus, Wilrijk, BelgiumlClinique St Pierre, Ottignies, BelgiummErasmus University Medical Centre, Rotterdam, The NetherlandsnLudwig-Maximilians Universität, Munich, GermanyoVU University Medical Centre Amsterdam, The NetherlandspAlgemeen Ziekenhuis St Lucas, Brugge, BelgiumqAlgemeen Ziekenhuis Damiaan Campus St Jozef, Oostende, BelgiumrAcademisch Ziekenhuis VUB, Jette, BelgiumsLeiden University Medical Centre, Leiden, Netherlands Available online 21 February 2008.

Refers to:

Initial combination therapy in early Crohn's diseaseThe Lancet, Volume 371, Issue 9613, 23 February 2008-29 February 2008, Pages 635-636 J SandbornAbstract | Full Text + Links | PDF (56 K)

Referred to by:

Initial combination therapy in early Crohn's diseaseThe Lancet, Volume 371, Issue 9613, 23 February 2008-29 February 2008, Pages 635-636 J SandbornAbstract | Full Text + Links | PDF (56 K)

Summary

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.

Correspondence to: Geert D'Haens, Department of Gastroenterology, Imelda Gastrointestinal Clinical Research Centre, Imelda General Hospital, Imeldalaan 9, B-2820 Bonheiden, Belgium

Volume 371, Issue 9613, 23 February 2008-29 February 2008, Pages 660-667