JAAD Study Validates 487-GEP to Guide JAK Inhibitor Selection in Moderate to Severe AD

A newly published prospective, multicenter clinical validation study in the Journal of the American Academy of Dermatology (JAAD) evaluated the clinical utility of a gene expression profile test designed to inform systemic treatment selection in moderate to severe atopic dermatitis (AD). The investigation assessed Castle Biosciences’ AdvanceAD-Tx, a noninvasive assay intended to provide objective molecular insight at the point of care for patients 12 years and older who are considering systemic therapy.^1,2

AdvanceAD-Tx analyzes lesional skin scrapings—without the need for biopsy—to measure the expression of 487 genes across 12 inflammatory and cutaneous biology pathways. Utilizing RNA sequencing data from 192 patients for algorithm development and an independent validation cohort of 110 patients with AD who were 12 years or older, the test classified patients into 2 molecular profiles: a JAK inhibitor (JAKi) Responder Profile (30.4%) and a Th2 Molecular Profile (69.6%). The profiles stratified patients according to the likelihood of response to JAKi therapy vs Th2-targeted treatments, the 2 predominant systemic therapeutic classes.²

“For years, systemic treatment decisions in AD have relied on clinical assessment and experience. Yet the disease is heterogeneous and biologically complex, driven by multiple immune pathways that vary from patient to patient. Until now, we haven’t had an objective way to identify which pathways are most active or which therapy class may be most effective,” wrote Aaron Farberg, MD, a double board-certified dermatologist and Mohs surgeon; chief medical officer at Bare Dermatology in Dallas, Texas; and investigator in the clinical research that led to the development of AdvanceAD-Tx, in a recent Dermatology Times feature.³

As systemic options for AD continue to expand, tools that help refine therapeutic selection based on underlying immune biology are of growing interest. The study’s findings contribute prospective data supporting a precision-medicine approach in AD, with potential implications for optimizing response rates, time to clearance, and patient-reported outcomes in routine clinical practice.

Results

Clinically, patients identified with a JAKi Responder Profile who received JAKi therapy demonstrated significantly superior outcomes compared to those treated with Th2-targeted therapies. Specifically, 45.5% of these patients achieved EASI 90 by 3 months vs only 8.3% on Th2-targeted therapies (P=.021). They reached EASI 90 3.8 times faster (P=.049) and exhibited higher rates of complete lesion clearance (vIGA-AD 0), absence of itch, and increased flare-free survival. Conversely, patients with a Th2 Molecular Profile showed no significant differences in clinical response between treatment classes, suggesting broad immunomodulatory effects of JAKi on Th2-driven disease but with no clear superiority over Th2 biologics in this subset.

The JAAD publication demonstrates the utility of molecular profiling in personalizing AD systemic therapy. The 487-GEP enables clinicians to identify patients likely to be “super-responders” to JAKi, facilitating more targeted treatment selection that could minimize ineffective therapy trials and improve patient quality of life. Importantly, the noninvasive sampling method and existing familiarity with scraping techniques support the feasibility of clinical implementation without cumbersome procedures.

“Atopic dermatitis can look similar on the surface, but the biology driving the disease can differ meaningfully from patient to patient,” said Mark G. Lebwohl, MD, senior study author, and dean for clinical therapeutics and professor and chairman emeritus of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York, in the news release. “This study shows that AdvanceAD-Tx can provide objective molecular insight to help clinicians better align systemic therapy choices with an individual patient’s disease biology earlier in the treatment journey and improve outcomes that matter to patients.”

Limitations include validation restricted to patients 12 years and older and the evolving landscape of emerging AD therapies not yet incorporated in the test. Nonetheless, this approach represents a substantive advance toward precision dermatology. Adoption of the 487-GEP test can provide a robust framework for individualized systemic treatment, enhancing efficacy and potentially reducing treatment burden in moderate to severe AD.

“Now we have the potential to move beyond the old system of picking and adjusting therapies by identifying the underlying immune pathways that drive AD to guide treatment more precisely. For our patients, it means faster relief and fewer setbacks. For dermatologists, it means greater confidence in knowing we are treating not only what we see on the surface but also the biology beneath it. That’s the promise of molecular insight, and it marks an exciting new era for care in AD,” Farberg concluded.

References

1. Prospective validation study in JAAD demonstrates Castle Biosciences’ AdvanceAD-Tx test identifies patients more likely to achieve faster and deeper responses with JAK inhibitor therapy in moderate-to-severe atopic dermatitis. News release. Castle Biosciences. February 19, 2026. Accessed February 20, 2026. https://ir.castlebiosciences.com/news/news-details/2026/Prospective-Validation-Study-in-JAAD-Demonstrates-Castle-Biosciences-AdvanceAD-Tx-Test-Identifies-Patients-More-Likely-to-Achieve-Faster-and-Deeper-Responses-with-JAK-Inhibitor-Therapy-in-Moderate-to-Severe-Atopic-Dermatitis/default.aspx
2. Silverberg JI, Eichenfield LF, Armstrong AW, et al. 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. Published online February 16, 2026. doi:10.1016/j.jaad.2026.02.034
3. Farberg AS. Precision medicine arrives in atopic dermatitis: guiding systemic treatment decisions through gene expression profiling. Dermatology Times. February 10, 2026. Updated February 13, 2026. Accessed February 20, 2026. https://www.dermatologytimes.com/view/precision-medicine-arrives-in-atopic-dermatitis-guiding-systemic-treatment-decisions-through-gene-expression-profiling