What is the role of janus kinase (JAK) inhibitors in the treatment of atopic dermatitis (eczema)?

Updated: Mar 13, 2019
  • Author: Brian S Kim, MD, MTR, FAAD; Chief Editor: William D James, MD  more...
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Answer

Multiple proinflammatory cytokines, including type 2 cytokines, are dependent on the JAK-STAT signaling pathway to mediate their effects. [53] Thus, in addition to cytokine receptor blockade, phase 2 clinical trials have been performed for both oral and topical JAK inhibitors. The oral JAK1-selective inhibitor upadacitinib (ABT-494) demonstrated significant improvement in terms of EASI compared with placebo at 16 weeks and improvement of itch severity as early as 1 week in a 2017 phase 2b clinical trial. [54] In support of the direct antipruritus effect of JAK inhibitors, a 2017 study identified that neuronal JAK1 signaling critically regulates AD-associated itch in mice, independently of any effect on the immune system. [19] Thus, these studies may explain why JAK inhibitors are demonstrating such unique anti-itch properties in clinical trials. Similarly, the JAK1/2-selective inhibitor, baricitinib, also demonstrated improvement in both itch and disease severity in patients with moderate-to-severe AD. [55] Finally, a phase 2a clinical trial for a topical JAK1/2 inhibitor (tofacitinib) was also found to be effective and demonstrated improvement in disease severity at 4 weeks compared with placebo. [56] Thus, both oral and topical JAK inhibition represents a potential new treatment strategy for AD. The topical formulations likely offer more opportunities to target milder forms of AD in contrast to the oral form, which, owing to its potency, is being investigated for moderate-to-severe AD.


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