Interleukin-6 inhibitors in the treatment of rheumatoid arthritis

Abstract

Recent developments in understanding the immunopathogenesis of rheumatoid arthritis (RA), combined with progress in biopharmaceutical development, have facilitated the introduction of novel immune modulating therapies for this progressive debilitating disorder. Efficacy achieved with certain agents, particularly the TNF inhibitors, has spurred the development of additional biologic agents targeting other components of the dysregulated immune response relevant to the etiology and sustenance of immune driven systemic inflammation characteristic of RA. Among these other potential targets is IL-6, a cytokine with effects on numerous cell types, including those involved in the pathogenesis of RA. Based on its activities, IL-6 appeared to be a viable target for autoimmune disease. Inhibitors of IL-6 were successful in animal models of autoimmune disease paving the way for subsequent studies in humans. The greatest experience to date has been with tocilizumab, a humanized monoclonal antibody specific for the IL-6 receptor (IL-6R). Beginning with open label studies, and progressing through larger and more rigorous controlled trials, tocilizumab has been shown to have significant Efficacy in patients with RA. Additional studies analyzing its effects in varied populations of RA patients, as well as greater detail concerning its longer-term tolerability and safety, will help define the ultimate role of tocilizumab and other future inhibitors of IL-6 activity as potential therapies for RA.