Selective JAK1 Inhibitors for the Treatment of Atopic Dermatitis: Focus on Upadacitinib and Abrocitinib

Abstract

Atopic dermatitis is a common, chronic, immune-mediated disease associated with several comorbidities. Elevated levels of T helper (Th)2, Th22, and also some Th1 and Th17 cytokines are found in atopic dermatitis skin lesions. Similar to psoriasis, there is a tendency towards increased use of more targeted therapies. However, there are still several unmet needs in the treatment of atopic dermatitis concerning long-term efficacy, tolerability, safety, route of administration, and cost. The increased knowledge of atopic dermatitis pathogenesis and the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways has allowed the development of new compounds to inhibit this intracellular signaling pathway implicated in atopic dermatitis-related immune responses. Currently, JAK inhibitors are an important focus of therapeutic research for atopic dermatitis. Upadacitinib and abrocitinib are oral small molecules that inhibit the JAK/STAT pathway by selectively blocking JAK1. Data from phase II and III trials are encouraging, revealing that JAK1 inhibitors are effective and well-tolerated agents for moderate-to-severe atopic dermatitis. Selective JAK1 inhibitors may represent an important therapeutic option to be included in the treatment algorithm of atopic dermatitis, owing to oral administration and a favorable safety and tolerability profile. In this article, we review the current evidence on the efficacy and safety of oral selective JAK1 inhibitors for the treatment of atopic dermatitis.