An Update on JAK Inhibitors in Skin Disease

Alexandra Norden, BA; Aislyn Oulee, BS; Sogol Stephanie Javadi, BS; Jashin J. Wu, MD

Disclosures

Cutis. 2022;109(3):122-124. 

In This Article

Abstract and Introduction

Introduction

A topic dermatitis (AD) is a chronic inflammatory skin disorder affecting 7% of adults and 13% of children in the United States.[1,2] Atopic dermatitis is characterized by pruritus, dry skin, and pain, all of which can negatively impact quality of life and put patients at higher risk for psychiatric comorbidities such as anxiety and depression.[3] The pathogenesis of AD is multifactorial, involving genetics, epidermal barrier dysfunction, and immune dysregulation. Overactivation of helper T cell (TH2) pathway cytokines, including IL-4, IL-13, and IL-31, is thought to propagate both inflammation and pruritus, which are central to AD. The JAK-STAT signaling pathway plays a pivotal role in the immune system dysregulation and exaggeration of TH2 cell response, making JAK-STAT inhibitors (or JAK inhibitors) strong theoretical candidates for the treatment of AD.[4] In humans, the Janus kinases are composed of 4 different members—JAK1, JAK2, JAK3, and tyrosine kinase 2—all of which can be targeted by JAK inhibitors.[5]

JAK inhibitors such as tofacitinib have already been approved by the US Food and Drug Administration (FDA) to treat various inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis; other JAK inhibitors such as baricitinib are only approved for patients with rheumatoid arthritis.[6,7] The success of these small molecule inhibitors in these immune-mediated conditions make them attractive candidates for the treatment of AD. Several JAK inhibitors are in phase 2 and phase 3 clinical trials as oral therapies (moderate to severe AD) or as topical treatments (mild to moderate AD). Currently, ruxolitinib (RUX) is the only topical JAK inhibitor that is FDA approved for the treatment of AD in the United States.[8] In this editorial, we focus on recent trials of JAK inhibitors tested in patients with AD, including topical RUX, as well as oral abrocitinib, upadacitinib, and baricitinib.

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