title: A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.hiroito@imed3.med.osaka-u.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takazoe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kusugami
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takehira
authors.initials: T
authors.lastname: Yamamura
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yoshizaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimoyama
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D019947:Receptors, Interleukin-6