title: Tocilizumab, a humanized anti-IL-6R antibody, as an emerging therapeutic option for rheumatoid arthritis: molecular and cellular mechanistic insights.
abstract: Pro-inflammatory cytokines play a major role in the initiation and maintenance of joint inflammation and destruction in rheumatoid arthritis (RA). The therapeutic success of biologics targeting tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and interleukin (IL)-6 receptor (IL-6R) has broadened the treatment options for RA. These agents have potential overlapping and discriminating biologic effects, as well as different pharmacological features. Tocilizumab (TCZ) is a humanized monoclonal antibody that binds and neutralizes IL-6R, resulting in the inhibition of various IL-6-mediated biological activities, including inflammation-related, immunomodulatory and tissue/matrix remodelling effects. Randomized, double-blind, controlled phase III studies and a number of early clinical observational studies have shown that treatment with TCZ results in rapid and sustained improvement in the signs and symptoms of RA among different patient populations. These studies have established the efficacy and safety of TCZ. Here, we review the pleiotropic functions of IL-6 and how it impinges on many aspects of RA pathogenesis, and highlight the clinical experience to date with TCZ as an emerging new treatment option for RA.
authors.affiliation: Chugai Pharmaceutical Co., Ltd. , Fuji-Gotemba Research Laboratories, Gotemba , Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Hashizume
authors.forename: Seng-Lai
authors.initials: SL
authors.lastname: Tan
authors.forename: Junichi
authors.initials: J
authors.lastname: Takano
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohsawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Hasada
authors.forename: Akira
authors.initials: A
authors.lastname: Hanasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ito
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mihara
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nishida
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D005109:Extracellular Matrix / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy / Q000639:trends; D015850:Interleukin-6 / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D019947:Receptors, Interleukin-6 / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab
keywords: actermra; anemia; atherosclerosis; inflammation; interleukin-6; rheumatoid arthritis; tocilizumab; tumor necrosis factor-alpha