JAK inhibitors in psoriasis: a promising new treatment modality.

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.

• Authors: Shawn G Kwatra, Tushar S Dabade, Cheryl J Gustafson, Steven R Feldman
• Journal: Journal of drugs in dermatology : JDD (J Drugs Dermatol) Vol. 11 Issue 8 Pg. 913-8 (Aug 2012) ISSN: 1545-9616 [Print] United States
• PMID: 22859235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cytokines
• Nitriles
• Piperidines
• Pyrazoles
• Pyrimidines
• Pyrroles
• ruxolitinib
• tofacitinib
• Janus Kinases

Topics

• Animals
• Cytokines (metabolism)
• Humans
• Janus Kinases (antagonists & inhibitors)
• Nitriles
• Piperidines
• Psoriasis (drug therapy, metabolism)
• Pyrazoles (therapeutic use)
• Pyrimidines (therapeutic use)
• Pyrroles (therapeutic use)
• Severity of Illness Index