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

Jonathan I Silverberg; Lawrence F Eichenfield; April W Armstrong; Jerry Bagel; Ben Lockshin; Erin Boh; John Koo; Aaron S Farberg; Matthew S Goldberg; Ann P Quick; Mark G Lebwohl

doi:10.1016/j.jaad.2026.02.034

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

J Am Acad Dermatol. 2026 Feb 16:S0190-9622(26)00230-6. doi: 10.1016/j.jaad.2026.02.034. Online ahead of print.

Authors

Affiliations

¹ Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
² Departments of Dermatology and Pediatrics, University of California San Diego School of Medicine, La Jolla, California.
³ Division of Dermatology, University of California Los Angeles, Los Angeles, California.
⁴ Director Eczema Center of New Jersey, Clinical Professor of Dermatology at The Icahn School of Medicine at Mount Sinai, East Windsor, New Jersey.
⁵ US Dermatology Partners, Rockville, Maryland.
⁶ Department of Dermatology, Tulane University School of Medicine, New Orleans, Louisiana.
⁷ Department of Dermatology, University of California, San Francisco School of Medicine, San Francisco, California.
⁸ Baylor Scott & White Health System, Dallas, Texas; Bare Dermatology, Dallas, Texas.
⁹ Research & Development, Castle Biosciences, Inc., Friendswood, Texas; Medical Affairs, Castle Biosciences, Inc., Friendswood, Texas; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: mgoldberg@castlebiosciences.com.
¹⁰ Research & Development, Castle Biosciences, Inc., Friendswood, Texas.
¹¹ Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.

PMID: 41707702
DOI: 10.1016/j.jaad.2026.02.034

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, itch, and flare frequency were reported. An ensemble algorithm (12 neural networks with 487 genes, 487-GEP) was developed to classify the 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 Eczema Area and Severity Index-90 (45.5% vs 8.3%, P = .021) 3.8 times faster (P = .049), reported "no itch" (45.5% vs 8.3%, P = .021), and increased flare-free rate (54.5% vs 16.7%, P = .041) versus Th2-targeted therapy. For those with a Th2 Molecular Profile, there were no statistical differences in Eczema Area and Severity Index-90 whether they used Th2-targeted (26.5%) or JAKi (33.3%, P = .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.

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