Tocilizumab, a humanized anti-IL-6R antibody, as an emerging therapeutic option for rheumatoid arthritis: Molecular and cellular mechanistic insights

Misato Hashizume, Seng Lai Tan, Junichi Takano, Kazunori Ohsawa, Ikuo Hasada, Akira Hanasaki, Ichiro Ito, Masahiko Mihara, Keiichiro Nishida

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)265-279
Number of pages15
JournalInternational Reviews of Immunology
Volume34
Issue number3
DOIs
Publication statusPublished - May 4 2015

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Keywords

  • Actermra
  • Anemia
  • Atherosclerosis
  • Inflammation
  • Interleukin-6
  • Rheumatoid arthritis
  • Tocilizumab
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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