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

• Main Author: Sakkas LI
• Format: Article
• Language: English
• Published: Dove Medical Press 2016-08-01
• Series: Drug Design, Development and Therapy
• Subjects: biologics; IL-6; IL-6 receptor; systemic sclerosis; tocilizumab
• Online Access: https://www.dovepress.com/spotlight-on-tocilizumab-and-its-potential-in-the-treatment-of-systemi-peer-reviewed-article-DDDT

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