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Perfil de expresión génica de 487 genes que guía la selección de terapia sistémica para mejorar los resultados en

Jonathan I Silverberg¹, Lawrence F Eichenfield², April W Armstrong³

¹Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, D.C.

Journal of the American Academy of Dermatology

|February 18, 2026

Abstracto

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.

Palabras clave:

perfil de expresión génica de 487 genes inhibidor de JAK perfil de respuesta a JAKi perfil molecular Th2 terapia dirigida a Th2 dermatitis atópica inflamación terapia sistémica

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