487-GEP Test Identifies Optimal Systemic Therapy for AD

A 487-gene expression profile (487-GEP) test may help personalize systemic therapy selection for patients with atopic dermatitis (AD), according to results from a prospective, multicenter trial presented by Dr. Jonathan Silverberg et al at the 2025 Fall Clinical Dermatology Conference.

The test, developed by Castle Biosciences, classifies patients into two molecular profiles: Th2 Molecular Profile and JAKi Responder Profile. This stratification was designed to guide the use of targeted biologics (eg, dupilumab) versus JAK inhibitors (JAKi) in order to avoid trial-and-error prescribing and optimize outcomes. In the validation cohort of 112 AD patients receiving systemic therapy, the 487-GEP test predicted significantly faster and deeper responses to JAK inhibitors in those with the JAKi Responder Profile.

By 3 months, patients with a JAKi Responder Profile treated with JAK inhibitors achieved:

• EASI 90 response 3.8 times faster (P = .046),

• Higher rates of Investigator Global Assessment (IGA) of 0 (clear skin),

• Greater “No Itch” rates (PROMIS® scale),

• Reduced flare frequency compared with those treated with Th2-targeted therapies.

Notably, these JAKi responders reached EASI 90 without requiring dose escalation.

Conversely, patients with a Th2 Molecular Profile had comparable outcomes whether treated with JAK inhibitors or Th2-targeted therapies, indicating that the test could help avoid overtreatment or ineffective regimens.

“Use of the 487-GEP identifies systemic therapy response and clinical use may lead to improved individual patient outcomes and satisfaction,” the authors concluded.