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.
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: Jun Gui; Michael Gober; Xiaoping Yang; Kanstantsin V Katlinski; Christine M Marshall; Meena Sharma; Victoria P Werth; Darren P Baker; Hallgeir Rui; John T Seykora; Serge Y Fuchs Journal: J Invest Dermatol Date: 2016-06-29 Impact factor: 8.551