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

Am J Clin Dermatol. 2020 Dec;21(6):783-798. doi: 10.1007/s40257-020-00548-6.

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.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Dermatitis, Atopic / diagnosis
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors*
  • Janus Kinase 1 / metabolism
  • Janus Kinase Inhibitors / administration & dosage*
  • Janus Kinase Inhibitors / adverse effects
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Severity of Illness Index
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Skin / drug effects
  • Skin / immunology
  • Skin / pathology
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology
  • Treatment Outcome

Substances

  • Heterocyclic Compounds, 3-Ring
  • Janus Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • upadacitinib
  • abrocitinib
  • JAK1 protein, human
  • Janus Kinase 1