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

Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii116-23. doi: 10.1136/annrheumdis-2012-202371. Epub 2012 Dec 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / physiopathology
  • Humans
  • Interleukin-17 / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-17
  • secukinumab