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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.
AuthorsMisato Hashizume, Seng-Lai Tan, Junichi Takano, Kazunori Ohsawa, Ikuo Hasada, Akira Hanasaki, Ichiro Ito, Masahiko Mihara, Keiichiro Nishida
JournalInternational reviews of immunology (Int Rev Immunol) Vol. 34 Issue 3 Pg. 265-79 (May 2015) ISSN: 1563-5244 [Electronic] England
PMID25099958 (Publication Type: Journal Article, Review)
Chemical References
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • Receptors, Interleukin-6
  • tocilizumab
Topics
  • Animals
  • Anti-Inflammatory Agents (immunology, therapeutic use)
  • Antibodies, Monoclonal, Humanized (therapeutic use)
  • Arthritis, Rheumatoid (immunology, therapy)
  • Extracellular Matrix (drug effects)
  • Humans
  • Immunomodulation
  • Immunotherapy (trends)
  • Interleukin-6 (metabolism)
  • Randomized Controlled Trials as Topic
  • Receptors, Interleukin-6 (immunology)

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