Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis

• Main Authors: Masahiko Mihara, Yoshiyuki Ohsugi, Tadamitsu Kishimoto
• Format: Article
• Language: English
• Published: Dove Medical Press 2011-02-01
• Series: Open Access Rheumatology : Research and Reviews
• Online Access: http://www.dovepress.com/tocilizumab-a-humanized-anti-interleukin-6-receptor-antibody-for-treat-a6493

Masahiko Mihara1, Yoshiyuki Ohsugi2, Tadamitsu Kishimoto31Product Research Department, Chugai Pharmaceutical Co Ltd, Fuji-Gotemba Research Laboratories, Shizuoka, Japan; 2Chugai Pharmaceutical Co Ltd, Tokyo, Japan; 3Laboratory of Immunoregulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, JapanAbstract: Interleukin (IL)-6 has a variety of biological functions. For example, it stimulates the production of acute-phase reactants (C-reactive protein and serum amyloid A) and hepcidin which interferes with iron recycling and absorption, causing iron-deficient anemia, and augments expression of vascular endothelial growth factor and receptor activator of nuclear factor-κB ligand in synovial cells, leading to neovascularization and osteoclast formation. IL-6 also acts on lymphocytes, not only on B cells to stimulate autoantibody production, but also on naïve T helper cells to promote Th17 cell differentiation. Thus, an imbalance between T cell subsets possibly contributes to development of rheumatoid arthritis. Several clinical studies have demonstrated that a humanized anti-IL-6 receptor antibody, tocilizumab, improves clinical symptoms in rheumatoid arthritis. Tocilizumab prevented radiographic progression of joint destruction by inhibiting cartilage/bone resorption. Tocilizumab also improved hematological abnormalities, including hypergammaglobulinemia, high levels of autoantibodies, and elevation of erythrocyte sedimentation rate and acute-phase proteins. Importantly, tocilizumab improved quality of life by reducing systemic symptoms, including fatigue, anemia, anorexia, and fever. These findings have confirmed that hyperproduction of IL-6 is responsible for the above clinical symptoms, including joint destruction. Many patients treated with tocilizumab achieved clinical remission associated with decreased serum IL-6, suggesting that IL-6 enhances autoimmunity. Tocilizumab is a new therapeutic option for rheumatoid arthritis.Keywords: interleukin-6, tocilizumab, efficacy, safety, mode of action