Philip J Mease1. 1. Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington, USA.
Abstract
PURPOSE OF REVIEW: In recent years, there has been an increasing understanding of the importance of the TH17 lineage of T cells and related cytokines, including interleukin (IL)17 and IL23, not only in the biology of innate host defense but also in the pathogenesis of inflammatory/autoimmune diseases. These diseases include psoriasis, psoriatic arthritis, the broader category of spondyloarthritides including ankylosing spondylitis and rheumatoid arthritis. It is postulated that in genetically predisposed individuals, external or internal stimuli such as microbial antigens, alterations in the intestinal microbiome, biomechanical stress and/or immunologic dysregulation may lead to an increased expression of cytokines such as IL23, which in turn stimulate the differentiation and activation of TH17 and other immune cells, which are a part of the innate immune system that trigger adaptive immune processes and chronic inflammatory diseases. Herein, we explore the effect of targeting this pathway therapeutically. RECENT FINDINGS: New drugs that are designed to inhibit steps in this pathway, the IL12/IL23 inhibitor, ustekinumab, the IL17A inhibitors secukinumab and ixekizumab, the IL17A receptor inhibitor, brodalumab, and the IL23 inhibitors guselkumab and tildrakizumab, have demonstrated significant effectiveness in treating these diseases, particularly psoriasis, psoriatic arthritis and ankylosing spondylitis. SUMMARY: This article reviews the relevant biology, efficacy and safety of new medications targeting the TH17 pathway, including inhibition of IL17 and IL23, particularly in psoriasis and psoriatic arthritis. Especially for patients who have not gained benefit from, lost effectiveness to or could not use antitumour necrosis factor (TNF) medications for safety or tolerability reasons, having effective medicines with an alternative mechanism of action will improve our ability to diminish disease activity impact on patient lives.
PURPOSE OF REVIEW: In recent years, there has been an increasing understanding of the importance of the TH17 lineage of T cells and related cytokines, including interleukin (IL)17 and IL23, not only in the biology of innate host defense but also in the pathogenesis of inflammatory/autoimmune diseases. These diseases include psoriasis, psoriatic arthritis, the broader category of spondyloarthritides including ankylosing spondylitis and rheumatoid arthritis. It is postulated that in genetically predisposed individuals, external or internal stimuli such as microbial antigens, alterations in the intestinal microbiome, biomechanical stress and/or immunologic dysregulation may lead to an increased expression of cytokines such as IL23, which in turn stimulate the differentiation and activation of TH17 and other immune cells, which are a part of the innate immune system that trigger adaptive immune processes and chronic inflammatory diseases. Herein, we explore the effect of targeting this pathway therapeutically. RECENT FINDINGS: New drugs that are designed to inhibit steps in this pathway, the IL12/IL23 inhibitor, ustekinumab, the IL17A inhibitors secukinumab and ixekizumab, the IL17A receptor inhibitor, brodalumab, and the IL23 inhibitors guselkumab and tildrakizumab, have demonstrated significant effectiveness in treating these diseases, particularly psoriasis, psoriatic arthritis and ankylosing spondylitis. SUMMARY: This article reviews the relevant biology, efficacy and safety of new medications targeting the TH17 pathway, including inhibition of IL17 and IL23, particularly in psoriasis and psoriatic arthritis. Especially for patients who have not gained benefit from, lost effectiveness to or could not use antitumour necrosis factor (TNF) medications for safety or tolerability reasons, having effective medicines with an alternative mechanism of action will improve our ability to diminish disease activity impact on patient lives.
Authors: Stefan von Berg; Yafeng Xue; Mia Collins; Antonio Llinas; Roine I Olsson; Torbjörn Halvarsson; Maria Lindskog; Jesper Malmberg; Johan Jirholt; Nina Krutrök; Marie Ramnegård; Marie Brännström; Anders Lundqvist; Matti Lepistö; Anna Aagaard; Jane McPheat; Eva L Hansson; Rongfeng Chen; Yao Xiong; Thomas G Hansson; Frank Narjes Journal: ACS Med Chem Lett Date: 2019-05-29 Impact factor: 4.345
Authors: Claus Johansen; Maike Mose; Pernille Ommen; Trine Bertelsen; Hanne Vinter; Stephan Hailfinger; Sebastian Lorscheid; Klaus Schulze-Osthoff; Lars Iversen Journal: Proc Natl Acad Sci U S A Date: 2015-10-12 Impact factor: 11.205