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JAK inhibitors: a new therapeutic tool for dermatologists

Presented by
Prof. Brett King, Yale School of Medicine, USA
AAD 2019
JAK inhibitors are a versatile novel drug class that will play a role in different dermatological indications because they block numerous cytokines that play a key role in the pathogenesis of different dermatologic conditions.

"The therapeutic tools of a dermatologist moved from less targeted therapies such as corticosteroids to more target therapies such as TNF-α blockers or cytokine blockers," explained Prof. Brett King (Yale School of Medicine, USA) [1]. The Janus kinase (JAK) family is composed of 4 members: JAK 1,2,3, and tyrosine kinase 2 (TYK2). They play a key role in growth, development, and differentiation [2]. More than 50 cytokines use the JAK-signal transducer and activator of transcription (STAT) pathway. JAK-STAT pathways are involved in signal transduction of many cytokines such as interferon-gamma (IFNγ), IFN-α, IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, IL-5, IL-6, IL-12, IL-13, and IL-23 [3].

JAK-inhibitors are currently registered for the treatment of RA, myeloproliferative diseases, and polycythaemia vera. Tofacitinib, ruxolitinib, and baricitinib are the most frequently used JAK inhibitors, and it has been shown that venous thrombosis is a signal for JAK inhibitors. “From experiences in RA, we know that especially in combination with non-steroidal anti-inflammatory drugs there is also a risk of gastrointestinal perforation − but this might look different, if these agents are used in dermatologic conditions,” concluded Prof. King.

1. King BA. Session S016, AAD Annual Meeting, 1-5 March 2019, Washington DC, USA.
2. Ciechanowicz P et al. J Dermatol Treat 2018;Nov 15 [Epub ahead of print].
3. Damsky W, King BA. J Am Acad Dermatol. 2017;76: 736–744

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