Clinical and Molecular Effects of Interleukin-17 Pathway Blockade in Psoriasis

Journal of Drugs in Dermatology : JDD
Lawrence GreenAbby Jacobson

Abstract

The interleukin-17 (IL-17) pathway plays a crucial role in the development of psoriasis. Briefly, naive T cells differentiate into helper T (Th17) cells through interaction with activated dendritic cells in the presence of IL-23, Th17 cells produce IL-17 cytokines, and keratinocytes stimulated by IL-17 ligands lead to aberrant differentiation and proliferation that promote production of proinflammatory chemokines and further recruitment of inflammatory cells, setting up a positive feedback loop. Currently, 3 US Food and Drug Administration–approved agents to treat psoriasis affect the IL-17 pathway: brodalumab, secukinumab, and ixekizumab. Brodalumab is a fully human IL-17 receptor A antagonist that blocks signaling of multiple downstream inflammatory cytokines involved in psoriasis. Secukinumab and ixekizumab selectively bind to and neutralize only IL-17A. Pharmacologic effects in patients with psoriasis include decreased keratinocyte hyperproliferation, reduced epidermal thickening, decreased inflammatory markers, and resolution of histologic and genomic features of psoriasis. In clinical trials, therapeutic doses of brodalumab, secukinumab, and ixekizumab have demonstrated skin clearance efficacy by psoriasis area and severi...Continue Reading

Citations

May 9, 2021·Journal of the American Academy of Dermatology·Li-Ran YeUNKNOWN Chinese Psoriasis Real World Evidence Research Group (CPRWERG)
Jul 14, 2021·ACR Open Rheumatology·Yidan GaoDeepak A Rao

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