Treatment of Crohn's disease with anti-IL-6 receptor antibody.
We have demonstrated, by using a T-cell transfer murine colitis model, that blocking interleukin 6 (IL-6) signaling with monoclonal antibody (mAb) to IL-6 receptor (IL-6R) abrogated apoptosis resistance of lamina propria T cells, suppressed the expression of vascular adhesion molecules, and successfully prevented and treated intestinal inflammation. Based on these results, we carried out an exploratory clinical trial to investigate the safety and efficacy of humanized anti-IL-6R mAb, MRA, in patients with Crohn's disease (CD). The results were promising, with 80% of the patients given every-2-week MRA infusions for 12 weeks showing a significantly higher clinical response rate as compared to 31% of the placebo-treated patients. Twenty percent of the patients on this regimen went into remission as compared to 0% of the placebo group. The acute-phase responses were normalized by a single MRA infusion, which strongly suggests IL-6 is the major cytokine responsible for their production in CD.
Ito
Hiroaki
H
Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D012074:Remission Induction
D000911:Antibodies, Monoclonal; D019947:Receptors, Interleukin-6; D002097:C-Reactive Protein