JAK inhibitors in psoriasis

A promising new treatment modality

Shawn Kwatra, Tushar S. Dabade, Cheryl J. Gustafson, Steven R. Feldman

Research output: Contribution to journalReview article

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, doubleblind, 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.

Original languageEnglish (US)
Pages (from-to)913-918
Number of pages6
JournalJournal of Drugs in Dermatology
Volume11
Issue number8
StatePublished - Aug 1 2012
Externally publishedYes

Fingerprint

Janus Kinases
Psoriasis
Therapeutics
Interleukin-23
T-Lymphocytes
Cytokine Receptors
Interleukin-17
Skin Diseases
PubMed
Placebos
Clinical Trials
Cytokines
Inflammation

ASJC Scopus subject areas

  • Dermatology

Cite this

Kwatra, S., Dabade, T. S., Gustafson, C. J., & Feldman, S. R. (2012). JAK inhibitors in psoriasis: A promising new treatment modality. Journal of Drugs in Dermatology, 11(8), 913-918.

JAK inhibitors in psoriasis : A promising new treatment modality. / Kwatra, Shawn; Dabade, Tushar S.; Gustafson, Cheryl J.; Feldman, Steven R.

In: Journal of Drugs in Dermatology, Vol. 11, No. 8, 01.08.2012, p. 913-918.

Research output: Contribution to journalReview article

Kwatra, S, Dabade, TS, Gustafson, CJ & Feldman, SR 2012, 'JAK inhibitors in psoriasis: A promising new treatment modality', Journal of Drugs in Dermatology, vol. 11, no. 8, pp. 913-918.
Kwatra S, Dabade TS, Gustafson CJ, Feldman SR. JAK inhibitors in psoriasis: A promising new treatment modality. Journal of Drugs in Dermatology. 2012 Aug 1;11(8):913-918.
Kwatra, Shawn ; Dabade, Tushar S. ; Gustafson, Cheryl J. ; Feldman, Steven R. / JAK inhibitors in psoriasis : A promising new treatment modality. In: Journal of Drugs in Dermatology. 2012 ; Vol. 11, No. 8. pp. 913-918.
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