Abstract

Tocilizumab (TCZ) is the first humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman's disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced cytokine release syndrome. The global clinical development program for TCZ provides a wealth of clinical data on intravenous TCZ, and more recent studies in patients with RA have provided evidence characterizing the role of intravenous TCZ as monotherapy in early disease and led to the introduction of a subcutaneous formulation of TCZ. In addition, recently published open-label extension and observational studies continue to support the long-term efficacy and safety of TCZ in both clinical trial and real-world settings. Given the involvement of IL-6-mediated signaling in inflammatory disorders, TCZ is also being investigated in other immunological diseases. In particular, a phase 2 trial on the safety and efficacy of subcutaneous TCZ in adults with systemic sclerosis shows clinically relevant improvements in skin sclerosis and lung function in these patients. Another anti-IL-6 receptor agent, sarilumab, targeting the IL6 receptor alpha subunit,was recently approved for the treatment of patients with RA, although long-term data for this biologic are not yet published. In this article we review the placement of TCZ in current treatment guidelines; recent clinical trial data, including quality of life in patients with RA; recent updates to the TCZ safety profile; recent investigations of TCZ in other immunological diseases; and the clinical development of other novel IL-6-targeted agents.

Highlights

  • Tocilizumab (TCZ) is the first humanized antiinterleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman’s disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced

  • Elevated levels of IL6 in serum, synovial fluid, and various tissues have been correlated with disease activity in patients with rheumatoid arthritis (RA) [2], juvenile idiopathic arthritis (JIA) [3, 4], Castleman’s disease [5, 6], systemic sclerosis (SSc) [7], giant cell arteritis (GCA) [8, 9], adult-onset Still’s disease (AOSD) [10], familial Mediterranean fever (FMF) [11, 12], Schnitzler’s syndrome [13, 14], polychondritis [15], and amyloidosis [1]

  • Published results are pending for the randomized phase 3 ASCERTAIN trial (ClinicalTrials.gov identifier NCT01768572), which evaluated SC sarilumab 150 mg or 200 mg every 2 weeks and TCZ-IV 4 mg/kg increased to 8 mg/kg based on clinical response in patients receiving background csDMARDs who had an inadequate response to or were intolerant of tumor necrosis factor (TNF) inhibitors

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Summary

Introduction

Tocilizumab (TCZ) is the first humanized antiinterleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman’s disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced. Elevated levels of IL6 in serum, synovial fluid, and various tissues have been correlated with disease activity in patients with rheumatoid arthritis (RA) [2], juvenile idiopathic arthritis (JIA) [3, 4], Castleman’s disease [5, 6], systemic sclerosis (SSc) [7], giant cell arteritis (GCA) [8, 9], adult-onset Still’s disease (AOSD) [10], familial Mediterranean fever (FMF) [11, 12], Schnitzler’s syndrome [13, 14], polychondritis [15], and amyloidosis [1] These associations suggest a pathogenetic role for IL-6 in multiple inflammatory conditions and form the basis of the rationale for the development of anti-IL-6 therapies. A more detailed review is provided of the placement of TCZ in recent RA treatment guidelines; recent TCZ clinical trial data, including quality of life (QOL) in patients with RA; recent updates to the TCZ safety profile; investigations in recently approved and nonapproved immunological diseases; and the clinical development of novel IL-6-targeted agents

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