Tofacitinib for the treatment of moderate-to-severe psoriasis

Abstract

Because of the increased knowledge about the underlying cytokine network in psoriasis, selective systemic agents for the treatment of moderate-to-severe psoriasis have been developed during the past decade. The marked upregulation of JAK/STAT pathways in psoriasis and the identification of multiple key mediators in psoriasis pathogenesis that signal through JAK/STAT pathways led to investigation of JAK proteins as potential therapeutic targets for psoriasis treatment. A novel JAK-STAT inhibitor, tofacitinib, has been tested in preclinical studies for the treatment of psoriasis. Considering the satisfactory safety profile and the encouraging efficacy observed in the Phase II and Phase III trials, tofacitinib may represent an important therapeutic to be included into the psoriasis paradigm.

Keywords:

• IL-23
• psoriasis
• small molecules
• Th17
• tofacitinib

Financial & competing interests disclosure

S Chimenti has received honoraria as a consultant and/or speaker for Pfizer; Pfizer manufacture tofacitinib. A Chiricozzi is supported by the 2012 Leo-Pharma Research Foundation Silver Award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Psoriasis is a chronic immune-mediated disease associated with several comorbidities that affects up to 2% of the population worldwide.

• Psoriasis is a immune-mediated disease involving both the innate and the adaptive immune compartments with multiple proinflammatory cytokines that play a crucial role in sustaining and amplifying immune cells recruitment and activation within lesional skin.

• Emerging studies investigated the role of JAK/STAT signaling pathway in the pathogenesis of psoriasis as it transduces signals for multiple pathogenic cytokines.

• Tofacitinib is a JAK inhibitor actually approved in several countries for the treatment of adult patients affected by moderate-to-severe rheumatoid arthritis.

• Tofacitinib is in advanced phase of development for the treatment of psoriasis, and has concluded Phase III.