Oral Janus kinase inhibitors for atopic dermatitis

Atopic dermatitis (AD) is one of the most common inflammatory skin conditions. The pathogenesis of AD involves skin barrier disruption and immune activation of T-helper (T_H)2 and T_H22 and varying degrees of T_H1 and T_H17 activation in various patient subtypes. Although AD is mainly driven by T_H2, the molecular and clinical heterogeneity of AD underscores the need for more efficacious treatments that target multiple immune axes. Janus kinase (JAK) inhibitors are novel therapeutics that broadly block many AD-related proinflammatory cytokines (interleukin [IL]-4, IL-5, IL-13, IL-31, thymic stromal lymphopoietin, interferon gamma, IL-12, IL-23, IL-17) across different immune pathways. Oral JAK inhibitors have been found to be efficacious in AD, with 2 (abrocitinib and upadacitinib) recently gaining US Food and Drug Administration approval and several others under investigation in clinical trials with promising results. These systemic agents have surpassed conventional thresholds of treatment response, with many patients achieving complete or almost complete skin clearance, and provide a fast-acting alternative therapy for patients who are not responsive to biologics or other conventional therapies. However, systemic JAK inhibitors come with health concerns, requiring additional long-term clinical trials to characterize their safety profile in patients with AD. This review summarizes the current literature on the safety and efficacy of oral JAK inhibitors in AD and discusses future directions for research.