Castle Biosciences Launches 487-Gene Test for AD Care

Castle Biosciences has announced the launch of AdvanceAD-Tx, a 487-gene expression profile (GEP) test designed to guide systemic treatment selection in patients aged 12 years and older with moderate to severe atopic dermatitis (AD). The test seeks to identify patients who are more likely to respond to Janus kinase inhibitor (JAKi) therapy versus T helper type 2 (Th2)-targeted biologic treatments, potentially enabling more precise, biology-driven treatment strategies in a heterogeneous disease population.¹

Treatment Selection Challenges

Despite the expansion of systemic treatment options for AD, including JAK inhibitors and Th2-targeted biologics such as dupilumab and tralokinumab, clinicians continue to face challenges in predicting which therapy will be most effective for a given patient. Empiric treatment approaches often lead to sequential therapy trials, delaying optimal disease control and increasing patient burden.

“Selecting the right systemic therapy for patients with AD can be a challenge, and too often patients end up cycling through multiple treatments before finding one that works,” said Jonathan I. Silverberg, MD, PhD, MPH, IDENTITY study author and associate professor of dermatology at the George Washington University School of Medicine and Health Sciences in Washington, DC, in a news release. “AdvanceAD-Tx is designed to uncover the biology driving each patient’s disease so we can better match the right treatment to the right patient from the start, helping them achieve relief faster and avoid unnecessary delays in care.”

Mechanism and Intended Use

AdvanceAD-Tx uses a 487-gene panel derived from lesional skin samples to assess molecular pathways associated with treatment response. Specifically, it classifies patients based on whether their gene expression patterns align with a JAKi responder profile, reflecting activation signatures that predict better response to JAK inhibition.

The test is intended for patients aged 12 and older with moderate to severe AD who are initiating or switching systemic therapy. According to Castle Biosciences, AdvanceAD-Tx builds on the company’s established molecular diagnostics infrastructure, integrating with existing laboratory workflows used for the DecisionDx test series.

The IDENTITY Study

Data from the IDENTITY study formed the basis of clinical validation for AdvanceAD-Tx. In this cohort, lesional skin samples were analyzed from patients with AD starting or switching systemic therapy to either a JAK inhibitor or a Th2-targeted biologic.²

Approximately 30.4% of tested samples demonstrated a JAKi responder profile. Among these patients, those treated with JAK inhibitors achieved significantly higher rates of Eczema Area and Severity Index 90% improvement (EASI-90) at three months compared with those receiving Th2-targeted therapy (45.5% vs. 8.3%, p=0.021).

Other secondary endpoints showed concordant trends:

• Validated Investigator Global Assessment (vIGA-AD) of clear (score 0): 36.4% vs. 0% (p=0.006)
• No itch by 3 months: 45.5% vs. 8.3% (p=0.021)
• Flare-free status: 54.5% vs. 16.7% (p=0.041)
• Time to EASI-90: Achieved 3.8 times faster in JAKi responders treated with a JAK inhibitor (p=0.049)

While these data suggest potential clinical utility for identifying patients more likely to respond to JAK inhibition, the study population size and real-world generalizability will require further validation in prospective settings.

Clinical Integration and Access

The company reports that AdvanceAD-Tx can be integrated within dermatology practices already familiar with Castle’s testing platforms, using standard biopsy workflows. The test is undergoing a limited commercial launch in November 2025, with expanded availability anticipated in 2026.

Castle Biosciences is pursuing multiple reimbursement pathways to support clinical adoption, although details regarding coverage or cost have not yet been disclosed.

According to Derek Maetzold, CEO of Castle Biosciences, the expansion into AD represents part of a broader strategy to extend precision medicine tools beyond oncology and rare dermatologic indications. The company estimates a $33-billion total addressable market for moderate to severe AD in the United States.

“AdvanceAD-Tx underscores Castle’s commitment to the dermatology community and developing clinically meaningful innovations that improve patient outcomes,” said Matthew Goldberg, MD, senior vice president, medical, at Castle Biosciences, in the release. “We’re applying the same disciplined, data-driven approach that made our DecisionDx franchise successful to an area where patients and clinicians need better tools.”

Clinical Considerations

For clinicians, the potential introduction of molecular profiling in AD represents an emerging precision medicine approach akin to that used in oncology and psoriasis. If validated in larger, independent studies, GEP-based stratification could reduce treatment trial-and-error, shorten time to disease control, and improve patient quality of life.

However, practical questions remain regarding test accessibility, turnaround time, cost-effectiveness, and integration into guideline-based care pathways. As with any novel biomarker-driven diagnostic, independent replication and long-term outcomes data will be key to determining its place in clinical practice.

References

1. Castle Biosciences launches AdvanceAD-Tx to help guide systemic treatment decision making in patients with moderate-to-severe atopic dermatitis. News release. Castle Biosciences. Published November 3, 2025. Accessed November 4, 2025. https://ir.castlebiosciences.com/news/news-details/2025/Castle-Biosciences-Launches-AdvanceAD-Tx-to-Help-Guide-Systemic-Treatment-Decision-Making-in-Patients-with-Moderate-to-Severe-Atopic-Dermatitis/default.aspx

2. Farberg A, Goldberg M, Quick A, et al. Gene expression differences identified in skin samples of mycosis fungoides, atopic dermatitis, and psoriasis. Poster presented at: Masterclasses in Dermatology February 16-19, 2024; Puerto Rico.