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Spotlight on tocilizumab and its potential in the treatment of systemic sclerosis

Authors Sakkas L

Received 27 June 2016

Accepted for publication 12 July 2016

Published 29 August 2016 Volume 2016:10 Pages 2723—2728

DOI https://doi.org/10.2147/DDDT.S99696

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Wei Duan


Lazaros I Sakkas

Department of Rheumatology and Clinical Immunology, Medical School, University of Thessaly, Larissa, Greece

Abstract:
Systemic sclerosis (SSc) is a multisystem disease characterized by extensive collagen deposition in skin and internal organs, fibrointimal microvasculopathy, and activation of the immune system. T cells and B cells can promote fibrosis in SSc. Interleukin (IL)-6 is implicated in the pathogenesis of SSc. IL-6 is increased in the peripheral blood and lesional skin from patients with SSc, and induces fibroblast collagen production directly and indirectly by inducing profibrotic M2 macrophages. IL-6 also induces Th17 differentiation and promotes B cell differentiation toward Ig-producing plasma cells. IL-6 is also implicated in the pathogenesis of SSc in animal models as it is increased in mice with bleomycin-induced fibrosis, whereas neutralization of IL-6 in these mice prevents skin fibrosis. IL-6 acts on cells by binding to IL-6 receptor (IL-6R) which is transmembrane or soluble, and then recruits the signal-transducing glycoprotein 130 which is ubiquitously expressed. Tocilizumab is an anti-IL-6R humanized monoclonal antibody that blocks IL-6-mediated signaling. Tocilizumab has been approved for the treatment of moderate-to-severe rheumatoid arthritis, for polyarticular and systemic juvenile idiopathic arthritis, and for Castleman’s disease, and is well tolerated. Case reports and a Phase II, randomized trial in SSc have shown some improvement of skin tightness and delayed deterioration of lung function. A Phase III randomized trial in SSc is anticipated.

Keywords: biologics, B cells, fibrosis, IL-6, IL-6 receptor

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