JAK inhibitors in psoriasis: a promising new treatment modality

J Drugs Dermatol. 2012 Aug;11(8):913-8.

Abstract

Background: Inflammatory cytokines play a crucial role in the pathophysiology of psoriasis. New therapies are targeting Janus kinases (JAKs), enzymes involved with transduction of cytokine receptor signaling.

Objective: Review the utility of JAK inhibitors in the treatment of psoriasis.

Methods: A review was performed using PubMed and Google to identify research relevant to the treatment of psoriasis using JAK inhibitors.

Results: In a CD18 mutant PL/J mouse model with T-cell dependent psoriasiform skin disease, the JAK inhibitor R348 reduced skin inflammation, with reductions in CD4+, CD8+, and CD25+ T-cell infiltration and systemic decreases of IL-17, IL-19, IL-22, IL-23 and TNF-α. Two JAK inhibitors, CP-690,550 (tasocitinib) and INCB018424 (ruxolitinib), were effective in psoriasis clinical trials. In a phase 1, randomized, double-blind, dose escalation trial for plaque psoriasis, CP-690,050 led to improvements in Psoriatic Lesion Severity Sum score at doses greater than 5 mg. A phase 2 trial showed CP-690,050 administered at 2, 5, and 15 mg twice daily resulted in a 75% reduction in Psoriasis Area and Severity Index (PASI) in 25%, 40.8%, and 66.7% of patients, respectively, for moderate to severe psoriasis. A phase 3 study of CP-690,550 for plaque psoriasis was begun in September 2010 (NCT01163253). INCB018424, another JAK inhibitor, was used topically at 3 doses (0.5%, 1%, 1.5%) in a phase 2B, double-blind, placebo-controlled trial, resulting in improved total lesion score, global assessment, and PASI for all doses.

Conclusion: Janus Kinase inhibitors are promising potential therapeutic options for psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Humans
  • Janus Kinases / antagonists & inhibitors*
  • Piperidines
  • Psoriasis / drug therapy*
  • Psoriasis / metabolism
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Pyrroles / therapeutic use*
  • Severity of Illness Index

Substances

  • Cytokines
  • INCB018424
  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • Janus Kinases