A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease.
OBJECTIVE
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] > or =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 > or =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.
Ito
Hiroaki
H
Department of Molecular Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.hiroito@imed3.med.osaka-u.ac.jp
Takazoe
Masakazu
M
Fukuda
Yoshihiro
Y
Hibi
Toshifumi
T
Kusugami
Kazuo
K
Andoh
Akira
A
Matsumoto
Takayuki
T
Yamamura
Takehira
T
Azuma
Junichi
J
Nishimoto
Norihiro
N
Yoshizaki
Kazuyuki
K
Shimoyama
Takashi
T
Kishimoto
Tadamitsu
T
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015415:Biomarkers; D003424:Crohn Disease / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D019947:Receptors, Interleukin-6