title: Effect of IL-17 receptor A blockade with brodalumab in inflammatory diseases.
abstract: IL-17 cytokines are expressed by a variety of cells and mediate host defence against extracellular pathogens. IL-17 is upregulated at sites of inflammation and can synergize with other cytokines, such as TNF-α, to amplify the inflammatory response. Activation of these signalling pathways has been hypothesized to contribute to the underlying pathogenesis of several inflammatory diseases, including psoriasis, RA, PsA and asthma. Thus the IL-17 signalling pathway is an attractive target for the development of therapeutic agents to modulate aberrant inflammatory responses. This review of the clinical development of therapeutic agents that target IL-17 signalling pathways in inflammatory diseases focuses on brodalumab, a human anti-IL-17 receptor A mAb. The cumulative findings of early clinical studies with anti-IL-17 agents, including brodalumab, secukinumab and ixekizumab, provide strong evidence for the role of IL-17 signalling in the pathophysiology of certain inflammatory diseases and support the potential use of these agents in treating these diseases.
authors.affiliation: Amgen, Thousand Oaks, CA anirula@me.com.
authors.forename: Ajay
authors.initials: A
authors.lastname: Nirula
authors.affiliation: Amgen, Thousand Oaks, CA.
authors.forename: Jon
authors.initials: J
authors.lastname: Nilsen
authors.affiliation: Amgen, Thousand Oaks, CA.
authors.forename: Paul
authors.initials: P
authors.lastname: Klekotka
authors.affiliation: Amgen, Thousand Oaks, CA.
authors.forename: Greg
authors.initials: G
authors.lastname: Kricorian
authors.affiliation: Amgen, Thousand Oaks, CA.
authors.forename: Ngozi
authors.initials: N
authors.lastname: Erondu
authors.affiliation: Amgen, Seattle, WA, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Towne
authors.affiliation: Amgen, Seattle, WA, USA.
authors.forename: Chris B
authors.initials: CB
authors.lastname: Russell
authors.affiliation: Amgen, Seattle, WA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Martin
authors.affiliation: Amgen, Seattle, WA, USA.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Budelsky
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D058990:Molecular Targeted Therapy; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology; D053722:Receptors, Interleukin-17 / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C109985:IL17RA protein, human; D053722:Receptors, Interleukin-17; C571216:brodalumab; C549079:ixekizumab; C555450:secukinumab
keywords: Crohn’s disease; asthma; brodalumab; interleukin-17; psoriasis; psoriatic arthritis; rheumatoid arthritis