title: 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.
  
  
  CONCLUSIONS
  Janus Kinase inhibitors are promising potential therapeutic options for psoriasis.
authors.affiliation: Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1071, USA.
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Kwatra
authors.forename: Tushar S
authors.initials: TS
authors.lastname: Dabade
authors.forename: Cheryl J
authors.initials: CJ
authors.lastname: Gustafson
authors.forename: Steven R
authors.initials: SR
authors.lastname: Feldman
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D009570:Nitriles; D010880:Piperidines; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D009570:Nitriles; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; D011758:Pyrroles; C540383:ruxolitinib; C479163:tofacitinib; D053612:Janus Kinases