Aaron Farberg, MD, Explains Gene Profiling in Atopic Dermatitis

Atopic dermatitis (AD) is widely recognized as a heterogeneous inflammatory skin disease, presenting with variable severity, chronicity, and response to therapy. The challenge in clinical management often lies in the unpredictability of patient responses to conventional treatments, ranging from topical corticosteroids and biologics to Janus kinase (JAK) inhibitors. During an interview with Dermatology Times at the 2025 Fall Clinical Dermatology Conference, Aaron Farberg, MD, a board-certified dermatologist and investigator, discussed emerging research on the use of gene expression profiling (GEP) to guide therapy selection in AD.

The 487-gene expression panel, developed by Castle Biosciences, represents a significant advancement in personalized dermatologic care. Unlike traditional approaches, which rely largely on trial-and-error prescribing, this GEP test leverages molecular insights to categorize patients based on underlying disease drivers. Specifically, the test analyzes gene expression patterns and organizes them into functional groups, allowing clinicians to identify patients who may respond preferentially to specific therapeutic classes. For instance, patients exhibiting a Th2-dominant profile may benefit more from targeted therapies such as IL-4 or IL-13 inhibitors, whereas others may demonstrate enhanced responsiveness to broader pathway modulation, including JAK inhibitors.

According to Farberg, the 487-GEP test offers practical advantages in routine dermatologic practice. Sample collection is minimally invasive, involving simple skin scrapings, which yield sufficient RNA for analysis. This approach circumvents the need for more invasive procedures like biopsies or tape stripping while providing reliable molecular data. The test’s predictive potential extends beyond standard efficacy endpoints such as EASI 90 and Investigator Global Assessment (IGA), incorporating patient-centered outcomes like itch severity and Dermatology Life Quality Index (DLQI). Importantly, early data suggest that profiling may allow for lower drug dosages while achieving optimal therapeutic responses, emphasizing a precision medicine approach that balances efficacy and safety.

The development and validation of the 487-GEP involved over 50 clinical sites and hundreds of participants, highlighting both the scalability and clinical interest in this technology. While gene expression profiling has long been applied in oncology, its integration into dermatology represents a novel expansion of personalized medicine tools into inflammatory skin disorders. Farberg notes that the algorithmic grouping of genes, rather than simple on/off expression, is central to the test’s utility, and ongoing computational analyses may further refine predictive capabilities.

Looking ahead, the implications of GEP extend beyond AD. The technology holds potential for broader application in other inflammatory and heterogeneous dermatologic conditions, enabling a more tailored approach to patient care. As the field advances, gene expression profiling may fundamentally shift treatment paradigms, moving from generalized therapy selection to data-driven, individualized management strategies that optimize outcomes and minimize unnecessary drug exposure.