Gastroenterology

Gastroenterology

Volume 116, Issue 5, May 1999, Pages 1029-1034
Gastroenterology

Alimentary Tract
Endoscopic and histological healing with infliximab anti–tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial,☆☆

Presented in part at the European Gastroenterology Week in Paris, 1996, and at the annual meeting of the American Gastroenterological Association in San Francisco, 1996.
https://doi.org/10.1016/S0016-5085(99)70005-3Get rights and content

Abstract

Background & Aims: Tumor necrosis factor (TNF) is a pivotal cytokine in intestinal inflammation. Controlled trials using a chimeric anti-TNF antibody (infliximab) have shown its efficacy in refractory Crohn's disease. Methods: Endoscopic and histological response to infliximab was investigated in a multicenter, randomized, double-blind, and placebo-controlled trial including 30 patients with active Crohn's disease undergoing ileocolonoscopy before and 4 weeks after intravenous administration of 5, 10, or 20 mg/kg of infliximab or placebo as a single infusion. Lesions were scored by means of the validated Crohn's Disease Endoscopic Index of Severity (CDEIS). Endoscopic biopsy specimens were taken during both procedures from 9 of 30 patients and scored by a single gastrointestinal pathologist. Results: CDEIS scores decreased significantly in most infliximab-treated patients without an apparent dose response. No endoscopic improvement was observed in the placebo group. The changes in CDEIS correlated highly with those of the Crohn's Disease Activity Index. At a histological level, disappearance of the inflammatory infiltrate was observed in infliximab-treated patients but not in placebo-treated ones; however, architectural changes persisted in most patients. Strictures developed in several patients. Conclusions: Clinical improvement after infliximab therapy in active Crohn's disease is accompanied by significant healing of endoscopic lesions and disappearance of the mucosal inflammatory infiltrate.

GASTROENTEROLOGY 1999;116:1029-1034

Section snippets

Materials and methods

Thirty patients with active refractory Crohn's disease were enrolled in an international randomized controlled trial comparing 5, 10, and 20 mg/kg infliximab with placebo as a single 2-hour infusion at four European centers (Leuven, Belgium; Amsterdam and Leiden, The Netherlands; and Leeds, England). To be eligible for the study, patients had to have had Crohn's disease for at least 6 months, with Crohn's Disease Activity Index (CDAI) scores between 220 and 400. Patients were excluded from the

Results

The patient and disease characteristics of the four treatment groups are shown in Table 1.

. Patient characteristics

Empty CellEmpty CellInfliximab
Empty CellPlacebo5mg/kg10 mg/kg20 mg/kgAll cA2
No. of patients877822
Sex (M/F)3/5 ¾ ¾3/59/13
Age (yr)a34.4 ± 9.830.1 ± 5.030.7 ± 8.733.1 ± 7.831.4 ± 7.1
Concomitant medication
 Azathioprine3/83/71/75/89/22
 Steroids5/84/73/74/811/22
aMean ± SEM.
Twelve patients had colonic, 6 purely ileal, and 12 ileocolonic Crohn's disease. The clinical improvement with infliximab treatment was accompanied

Discussion

Therapeutic options in refractory Crohn's disease are limited. Although the widespread use of azathioprine and 6-mercaptopurine has dramatically reduced the number of intractable cases, patients not responding to this therapy often become dependent on corticosteroids and eventually have to undergo debilitating surgical resections.14, 15, 16, 17, 18 The advent of immune-targeted therapy opens a wide range of new therapeutic possibilities, the most convincing clinical results to date having been

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    Address requests for reprints to: Geert D'Haens, M.D., Ph.D., Department of Internal Medicine, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. e-mail: [email protected]; fax: (32) 16-3488-58.

    ☆☆

    Supported in part by Centocor, Inc., Malvern, Pennsylvania.

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