title: Effect of IL-17A blockade with secukinumab in autoimmune diseases.
abstract: 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.
authors.affiliation: Autoimmunity, Transplantation and Inflammation Disease Area, Novartis Institutes for BioMedical Research, Basel CH-4002, Switzerland. office.patel@novartis.com
authors.forename: Dhavalkumar D
authors.initials: DD
authors.lastname: Patel
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
authors.forename: Frank
authors.initials: F
authors.lastname: Kolbinger
authors.forename: Christian
authors.initials: C
authors.lastname: Antoni
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D020381:Interleukin-17; C555450:secukinumab