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

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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.

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  1. Department of Dermatology, Centro Hospitalar Universitário do Porto, Edifício das Consultas Externas, Ex. CICAP, Rua D. Manuel II, s/n, 4100, Porto, Portugal

    Sandra Ferreira & Tiago Torres

  2. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, USA

    Emma Guttman-Yassky

  3. Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal

    Tiago Torres

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Sandra Ferreira has no conflicts of interest that are directly relevant to the content of this article. Emma Guttman declares the following conflicts of interest: AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boehringer-Ingelheim, Cara Therapeutics, Celgene, Concert, DBV, Dermira, Dermavant, DS Biopharma, Eli Lilly, EMD Serono, Escalier, Galderma, Glenmark, Innovaderm, Janssen Pharmaceuticals, Kiniksa, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Novan, Pfizer, Ralexar, RAPT Therapeutics, Regeneron, Sanofi, Sienna Biopharma, UCB, and Union Therapeutics. Tiago Torres declares the following conflicts of interest: AbbVie, Amgen, Almirall, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, Biocad, LEO Pharma, Eli Lilly, MSD, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, and Sandoz.

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Sandra Ferreira, Emma Guttamn, and Tiago Torres had the idea for the article, performed the literature search and data analysis, and drafted and critically revised the work.

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Ferreira, S., Guttman-Yassky, E. & Torres, T. Selective JAK1 Inhibitors for the Treatment of Atopic Dermatitis: Focus on Upadacitinib and Abrocitinib. Am J Clin Dermatol 21, 783–798 (2020). https://doi.org/10.1007/s40257-020-00548-6

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