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.

• Authors: Sandra Ferreira, Emma Guttman-Yassky, Tiago Torres
• Journal: American journal of clinical dermatology (Am J Clin Dermatol) Vol. 21 Issue 6 Pg. 783-798 (Dec 2020) ISSN: 1179-1888 [Electronic] New Zealand
• PMID: 32776305 (Publication Type: Journal Article, Review)

Chemical References

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

Topics

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