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Effect of IL-17A blockade with secukinumab in autoimmune diseases

Patel, Dhavalkumar and Kolbinger, Frank and Lee, David and Antoni, Christian (2012) Effect of IL-17A blockade with secukinumab in autoimmune diseases. Annals of the rheumatic diseases. ISSN 0003-4967

Abstract

The importance of Th17 cells in the pathophysiology of autoimmune disorders has become increasingly appreciated in the past several years. Genetic studies and correlative expression data in diseased tissues have pointed to the role of Th17 cells in the pathogenesis of psoriasis, inflammatory bowel disease, and seronegative spondyloarthropathies. While it is known that Th17 cells produce the pro-inflammatory cytokine interleukin (IL)-17A, recent research has demonstrated that IL-17A is also expressed by multiple lineages of the innate immune system, including mast cells, neutrophils, dendritic cells, gammadelta-T cells, macrophages, and natural killer cells. Th17 cells also express other effector cytokines, such as IL-17F and IL-22. It can thus be expected that inhibiting IL-17A as a therapeutic target in autoimmune disease would exert different physiologic effects than suppressing Th17 activity. Early clinical data are now available on secukinumab (AIN 457), a recombinant, highly selective, fully human monoclonal anti-IL17A antibody of the IgG1/kappa isotype, enabling a preliminary assessment of the effects of IL-17A inhibition in multiple autoimmune diseases. Rapid and sustained symptom reductions in psoriasis, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis have been observed in secukinumab-treated patients, with no important safety signals. In conjunction with data on the humanized anti-IL-17A monoclonal antibody ixekizumab (LY2439821) and the fully human anti-IL-17RA monoclonal antibody brodalumab (AMG 827), these findings provide evidence for the role of IL-17A to the pathophysiology of autoimmune disease and suggest the potential value of targeting this cytokine.

Item Type: Article
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Additional Information: Note--this is an invited review. The manuscript is supported and fully vetted with the AIN457/development communications team. Draft version with active comments submitted because of a very short prep time and proximal deadline
Keywords: IL17, autoimmunity, psoriasis, AIN457, secukinumab
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/7928

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