Gastroenterology

Gastroenterology

Volume 126, Issue 4, April 2004, Pages 989-996
Gastroenterology

Clinical-alimentary tract
A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease

https://doi.org/10.1053/j.gastro.2004.01.012Get rights and content

Abstract

Background & Aims: Interleukin-6 (IL-6) regulates immune response and inflammation. We carried out a pilot placebo-controlled study to investigate the efficacy, pharmacokinetics, and safety of MRA, a humanized monoclonal antibody to IL-6 receptor, in patients with active Crohn’s disease. Methods: Thirty-six patients with active Crohn’s disease (Crohn’s Disease Activity Index [CDAI] ≥150) were randomly assigned to receive biweekly intravenous infusion of either placebo, MRA, or MRA/placebo alternately for 12 weeks at a dose of 8 mg/kg. The study’s primary end point was a clinical response rate that was defined as a reduction of CDAI ≥70. Results: At the final evaluation, 80% of the patients (8 of 10) given biweekly MRA had a clinical response as compared with 31% of the placebo-treated patients (4 of 13; P = 0.019). Twenty percent of the patients (2 of 10) on this regimen went into remission (CDAI <150), as compared with 0% of the placebo-treated patients (0 of 13). The clinical response rate of the every-4-week regimen was 42% (5 of 12). The serum concentrations of MRA were detected at 2 weeks after every infusion, at which time acute phase responses were completely suppressed; however, they were not suppressed at 4 weeks. Endoscopic and histologic examination showed no difference between MRA and placebo groups. The incidence of adverse events was similar in all the groups. Conclusions: This is the first clinical trial of humanized anti-IL-6 receptor monoclonal antibody in Crohn’s disease. A biweekly 8 mg/kg infusion of MRA was well tolerated, normalized the acute-phase responses, and suggests a clinical effect in active Crohn’s disease.

Section snippets

Patients

Patients with CD, diagnosed in terms of history and radiologic or endoscopic intestinal appearance, who were at least 20 years of age were eligible for the study. Patients were to have a score on the Crohn’s Disease Activity Index (CDAI)8 ≥150, which indicates active CD, and abnormal serum levels of CRP. Patients were screened for eligibility at least 2 weeks before treatment. A total of 36 patients were screened, and all patients underwent randomization at 7 study centers in Japan between May

Patient characteristics

Thirty-six patients were randomly assigned to the M2W, M4W, or placebo group (Figure 1). Demographic data for the randomized patients are given in Table 1. There were no significant differences in age, sex, duration of disease, CDAI scores, or laboratory test values including CRP levels at baseline among the groups. All the patients had colonic disease with or without involvement of the small intestine. There were no significant differences in the number of the patients who had undergone

Discussion

Our study is the first randomized placebo-controlled trial of anti-IL-6R mAb MRA in the treatment of patients with active CD. Although this is a preliminary study, the results presented here show that the therapy with MRA for CD is safe and well tolerated and suggests a beneficial effect.

The clinical response rate of the M2W group was higher than that of the M4W group. The different response rate between the MRA groups might be attributable to a continuous suppression of acute-phase reactants

Acknowledgements

The authors wish to thank Paul Langman, Ph.D., for his valuable assistance with the preparation of the English version of this paper.

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Supported by Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.

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