Targeting of interleukin-17 in the treatment of psoriasis

Abstract

Ann Sophie Lønnberg, Claus Zachariae, Lone SkovDepartment of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkAbstract: “Psoriasis” is a chronic immune-mediated inflammatory disorder with epidermal hyperplasia. There is some evidence that the cytokine interleukin-17A (often known as IL-17), which is mainly produced by Th17 cells, has a role in the pathogenesis of psoriasis. “IL-17” is a pro-inflammatory cytokine mainly important in the host's defense against extracellular bacteria and fungi. The three new therapies with biologic drugs – brodalumab, secukinumab, and ixekizumab – all target the IL-17 signaling pathway. Secukinumab and ixekizumab neutralize IL-17A, while brodalumab blocks its receptor. Results from clinical trials have shown marked improvements in disease severity in patients with moderate-to-severe plaque psoriasis, using any of these three drugs. The biologic agents were generally well tolerated, but the duration of the trials was relatively short. In this review, we focus on the role of the IL-17 cytokine family in the pathogenesis of psoriasis; the efficacy, safety, and tolerability of brodalumab, secukinumab, and ixekizumab in clinical trials; and possible differences between targeting of the IL-17A receptor and targeting of the IL-17A ligand.Keywords: anti-IL-17 agents, IL-17, brodalumab, secukinumab, ixekizumab, psoriasis