Newer treatments of psoriasis regarding IL-23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors

Dermatol Ther. 2017 Nov;30(6). doi: 10.1111/dth.12555. Epub 2017 Oct 10.

Abstract

The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23). Phosphodiesterase inhibitors exert an anti-inflammatory action and their most common group is the PDE4 family. PDE4 inhibits cAMP, which reduces the inflammatory response of the pathway of Th helper lymphocytes, Th17, and type 1 interferon which modulates the production of anti-inflammatory cytokines such as IL-10 interleukins. The Janus kinase (JAK) signaling pathway plays an important role in the immunopathogenesis of psoriasis. Tofacitinib suppresses the expression of IL-23, IL-17A, IL-17F, and IL-22 receptors during the stimulation of lymphocytes. Ruxolitinib is a selective inhibitor of JAK1 and JAK2 kinases and the JAK-STAT signaling pathway. This article is a review of the aforementioned drugs as described in the latest available literature.

Keywords: IL-23 inhibitors; JAK inhibitors; PDE4 inhibitors; biological drugs; immune-modulating; psoriasis; therapy; treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / immunology
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
  • Dermatologic Agents / adverse effects
  • Dermatologic Agents / therapeutic use*
  • Humans
  • Interleukin-23 Subunit p19 / antagonists & inhibitors*
  • Interleukin-23 Subunit p19 / immunology
  • Interleukin-23 Subunit p19 / metabolism
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / therapeutic use*
  • Janus Kinases / antagonists & inhibitors*
  • Janus Kinases / metabolism
  • Molecular Targeted Therapy
  • Phosphodiesterase 4 Inhibitors / adverse effects
  • Phosphodiesterase 4 Inhibitors / therapeutic use*
  • Psoriasis / diagnosis
  • Psoriasis / drug therapy*
  • Psoriasis / enzymology
  • Psoriasis / immunology
  • Signal Transduction / drug effects
  • Skin / drug effects*
  • Skin / enzymology
  • Skin / immunology
  • Skin / pathology
  • Treatment Outcome

Substances

  • Dermatologic Agents
  • IL23A protein, human
  • Interleukin-23 Subunit p19
  • Janus Kinase Inhibitors
  • Phosphodiesterase 4 Inhibitors
  • Janus Kinases
  • Cyclic Nucleotide Phosphodiesterases, Type 4