The 487-gene expression profile test guides systemic therapy selection to improve outcomes for patients with atopic...

Current atopic dermatitis (AD) therapy selection does not account for molecular drivers of disease, contributing to inadequate disease control for half of patients.

Develop and validate a gene expression profile (GEP) test to guide AD systemic therapy selection.

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).

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).

Validation was limited to patients ≥12 years.

The 487-GEP identifies AD patients more likely to benefit from JAKi than Th2-targeted therapies.