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

DD Patel, DM Lee, F Kolbinger, C Antoni - Annals of the rheumatic …, 2013 - ard.bmj.com
DD Patel, DM Lee, F Kolbinger, C Antoni
Annals of the rheumatic diseases, 2013ard.bmj.com
Genetic studies and correlative expression data in diseased tissues have pointed to the role
of interleukin (IL)-17 and Th17 cells in the pathogenesis of autoimmune disorders such as
psoriasis, inflammatory bowel disease and seronegative spondyloarthropathies. Th17 cells
are known to produce the proinflammatory cytokine IL-17A as well as other effector
cytokines, including IL-17F and IL-22. Recent research has demonstrated that IL-17A is also
expressed by multiple lineages of the innate immune system, including mast cells …
Genetic studies and correlative expression data in diseased tissues have pointed to the role of interleukin (IL)-17 and Th17 cells in the pathogenesis of autoimmune disorders such as psoriasis, inflammatory bowel disease and seronegative spondyloarthropathies. Th17 cells are known to produce the proinflammatory cytokine IL-17A as well as other effector cytokines, including IL-17F and IL-22. Recent research has demonstrated that IL-17A is also expressed by multiple lineages of the innate immune system, including mast cells, neutrophils, dendritic cells, γδ-T cells, macrophages and natural killer cells. It can thus be expected that the inhibition of IL-17A as a therapeutic target in autoimmune disease would exert different physiological effects than the suppression of Th17 cell activity. Early clinical data are now available on secukinumab (AIN457), a recombinant, highly selective, fully human monoclonal anti-IL-17A antibody of the IgG1/κ 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 overt safety signals. In conjunction with studies using the humanised anti-IL-17A monoclonal antibody (mAb) ixekizumab (LY2439821) and the fully human anti-IL-17RA mAb brodalumab (AMG 827), the findings on secukinumab provide evidence for the role of IL-17A in the pathophysiology of autoimmune disease and suggest the potential value of targeting this cytokine.
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