Novel therapy for Crohn's disease targeting IL-6 signalling.
The aetiology of Crohn's disease (CD) remains unknown, however, the importance of pro-inflammatory cytokines including IL-6 has been shown. IL-6 can transduce its signal into the cells lacking membrane-bound receptors by forming a complex with soluble IL-6R (sIL-6R). To pursue the therapeutic potential of IL-6 signalling blockade for CD, anti-IL-6R monoclonal antibody (mAb) was introduced to experimental colitis, and successfully prevented and treated intestinal inflammation by suppressing vascular adhesion molecules and by inducing lamina propria T cell apoptosis. Based on these results, the clinical trial of humanised anti-IL-6R mAb, MRA, was carried out. Eighty per cent of the patients given twice-weekly MRA had a significantly better clinical response rate as compared to 31% of the placebo-treated patients. The response rate of the every-4-weeks regimen was 42%. The incidence of adverse events was similar in all groups. These data strongly suggest a therapeutic potential of MRA for CD.
Ito
Hiroaki
H
Osaka University Graduate School of Medicine, Department of Molecular Medicine, 2-2 Yamada-oka, Suita, Japan. hiroito@imed3.med.osaka-u.ac.jp
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors