AdvanceAD-Tx Gene Expression Profile Test May Help Guide Systemic Therapy Selection in Atopic Dermatitis

“We now finally have a test that tells us, with a great degree of accuracy, whether the patient is likely to respond just to a biologic or is likely to need something more,” said Mark Lebwohl, MD, in a recent interview discussing the benefits of the AdvanceAD-Tx 487-gene expression profile (GEP) test for moderate to severe atopic dermatitis (AD).

Lebwohl, dermatologist, Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai in New York, and professor and chairman emeritus of the Kimberly and Eric J. Waldman Department of Dermatology at Mount Sinai, described how Castle Biosciences’ 487-GEP test may help clinicians identify the most appropriate systemic therapy for patients with AD earlier in the treatment journey. Lebwohl was an author of a recent prospective, multicenter clinical validation study in the Journal of the American Academy of Dermatology, which evaluated the clinical utility of the 487-GEP test.¹

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Lebwohl noted that dermatology practices have seen a surge in patients with AD in recent years, driven in part by increased awareness and the availability of targeted therapies. “Patients finally realize that there is something that really works,” he said, explaining that individuals with eczema are now presenting to dermatology clinics “in droves.”

Expanding Options but Persistent Treatment Gaps

Historically, systemic treatment options for severe AD included agents such as systemic corticosteroids, methotrexate, cyclosporine, and azathioprine. These therapies carry substantial safety concerns and are generally unsuitable for long-term disease control.²

More recently, biologic therapies—including dupilumab, tralokinumab, lebrikizumab, and nemolizumab—have significantly improved the safety profile of systemic treatment. However, Lebwohl emphasized that a meaningful proportion of patients fail to achieve adequate disease control with biologics. “They don’t work adequately well for close to a third of patients,” he said.

Oral JAK inhibitors provide another effective treatment option and often demonstrate rapid and robust clinical responses. Yet their prescribing information typically recommends use after other systemic therapies because of boxed safety warnings, including risks related to infections, malignancy, thrombosis, and cardiovascular events. In clinical practice, Lebwohl noted that serious cardiovascular or thrombotic events appear uncommon in the shorter-term dermatologic populations studied, although infections do occur at higher rates.

Addressing Therapeutic Uncertainty

The availability of multiple systemic options leaves clinicians with a key question: which patients should begin therapy with a biologic, and which may require a JAK inhibitor to achieve meaningful disease control?

According to Lebwohl, the AdvanceAD-Tx 487-GEP test offers a data-driven approach to that decision. The assay analyzes a 487-gene expression signature to help predict whether a patient is likely to respond adequately to biologic therapy or whether they may require a JAK inhibitor.

Potential Impact on Clinical Practice

Lebwohl described the test as “practice-changing,” particularly for patients who would otherwise spend months cycling through therapies with incomplete benefit. Patients who are unlikely to respond sufficiently to biologics may instead be directed earlier to JAK inhibitor therapy, potentially reducing prolonged disease burden, lost productivity, and repeated follow-up visits driven by inadequate control.

By helping clinicians select a more effective therapy from the outset, Lebwohl suggested the GEP test could streamline treatment decision-making and reduce the frustrating cycle of partial responses and delayed escalation.

Ultimately, he said, the goal is straightforward: “We’re in this to make patients better—and this helps us go right to the treatment that’s going to work.”

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 March 10, 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. 2026; S0190-9622(26)00230-6. doi:10.1016/j.jaad.2026.02.034