The 487-gene expression profile test guides systemic therapy selection to improve outcomes for patients with atopic dermatitis: Results from a prospective trial

Authors

• Jonathan I. Silverberg, Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, D.C.
• Lawrence F. Eichenfield, Departments of Dermatology and Pediatrics, University of California San Diego School of Medicine, La Jolla, CA.
• April W. Armstrong, Division of Dermatology, University of California Los Angeles, Los Angeles, CA.
• Jerry Bagel, Director Eczema Center of New Jersey, Clinical Professor of Dermatology at The Icahn School of Medicine at Mount Sinai, East Windsor, NJ.
• Ben Lockshin, US Dermatology Partners, Rockville, MD.
• Erin Boh, Department of Dermatology, Tulane University School of Medicine, New Orleans, LA.
• John Koo, Department of Dermatology, University of California, San Francisco School of Medicine, San Francisco, CA.
• Aaron S. Farberg, Baylor Scott & White Health System, Dallas, TX; Bare Dermatology, Dallas, TX.
• Matthew S. Goldberg, Castle Biosciences, Inc., Friendswood, TX; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: mgoldberg@castlebiosciences.com.
• Ann P. Quick, Castle Biosciences, Inc., Friendswood, TX.
• Mark G. Lebwohl, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.

Document Type

Journal Article

Publication Date

2-16-2026

Journal

Journal of the American Academy of Dermatology

DOI

10.1016/j.jaad.2026.02.034

Keywords

487-gene expression profile; JAK inhibitor; JAKi Responder Profile; Th2 Molecular Profile; Th2-targeted therapy; atopic dermatitis; inflammation; systemic therapy

Abstract

BACKGROUND: Current atopic dermatitis (AD) therapy selection does not account for molecular drivers of disease, contributing to inadequate disease control for half of patients. OBJECTIVE: Develop and validate a gene expression profile (GEP) test to guide AD systemic therapy selection. METHODS: In a prospective study, AD or psoriasis lesion skin scrapings were analyzed by RNA-Seq, and treatments and outcomes including eczema area and severity index (EASI), itch, and flare frequency were reported. An ensemble algorithm (12 neural networks with 487 genes, 487-GEP) was developed to classify probability of AD or psoriasis treatment response (n=192) and independently validated in AD patients (n=110). RESULTS: AD patients classified by the 487-GEP as JAK inhibitor (JAKi)-Responder-Profile (30.4%) and treated with a JAKi achieved significantly higher rates of EASI-90 (45.5% vs. 8.3%, p=0.021) 3.8-times faster (p=0.049), reported "no itch" (45.5% vs. 8.3%, p=0.021), and increased flare-free rate (54.5% vs. 16.7%, p=0.041) versus Th2-targeted therapy. For those with a Th2 Molecular Profile, there were no statistical differences in EASI-90 whether they used Th2-targeted (26.5%) or JAKi (33.3%, p=0.728). LIMITATIONS: Validation was limited to patients ≥12 years. CONCLUSIONS: The 487-GEP identifies AD patients more likely to benefit from JAKi than Th2-targeted therapies.

APA Citation

Silverberg, Jonathan I.; Eichenfield, Lawrence F.; Armstrong, April W.; Bagel, Jerry; Lockshin, Ben; Boh, Erin; Koo, John; Farberg, Aaron S.; Goldberg, Matthew S.; Quick, Ann P.; and Lebwohl, Mark G., "The 487-gene expression profile test guides systemic therapy selection to improve outcomes for patients with atopic dermatitis: Results from a prospective trial" (2026). GW Authored Works. Paper 8705.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8705

Department

Dermatology