Determining Biologic or JAKi Efficacy for Patients With Moderate to Severe AD Through GEP Testing

“We've never had a biomarker that identified which treatment would work best for atopic dermatitis. So, the test is easy to do,” said Mark Lebwohl, MD, in a recent interview discussing 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.^1,2

In this first part of his interview, Lebwohl discussed treatment gaps that have existed with AD and the potential impact of AdvanceAD-Tx on clinical practice.

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Biologic Responders and the Role of Environmental Triggers

According to Lebwohl, patients identified by the GEP test as having a Th2-dominant profile are typically directed toward one of the 4 currently available biologic therapies: dupilumab, tralokinumab, lebrikizumab, or nemolizumab. Although these agents are generally well tolerated and patients report high satisfaction, Lebwohl emphasized that AD's waxing and waning course—compounded by environmental triggers—can undermine even initially adequate biologic responses. In his Northeast practice, cold, dry air and steam heat are among the most common drivers of exacerbation. As a result, some patients who were initially managed on biologics have since transitioned to JAK inhibitors following disease flares that exceeded what their biologic therapy could control.

Off-Label Dose Escalation and Its Limits

For patients achieving partial but insufficient responses on biologics, Lebwohl described the practice of off-label dose escalation; for example, shortening dupilumab dosing intervals from every 2 weeks to weekly. While drug manufacturers have been relatively accommodating in supporting access, many patients escalated in this manner still do not achieve adequate disease control, and environmental flares continue to occur. These are precisely the patients, Lebwohl noted, for whom the GEP test is most clinically useful.

JAK Inhibitor Efficacy and Contextualizing Safety

Head-to-head clinical trial data have demonstrated that even low-dose JAK inhibitors outperform biologics in efficacy for some patients, with higher doses offering additional benefit. Lebwohl acknowledged the boxed warnings associated with JAK inhibitors, particularly infection risk, but urged clinicians to contextualize these risks for patients. He noted that data on major adverse cardiovascular events with JAK inhibitors compare favorably to those reported with over-the-counter NSAIDs such as ibuprofen, a comparison he routinely shares with patients to provide reassurance.

Test Administration and Access

The GEP test is straightforward to perform in a clinical setting, requiring only a skin scale sample collected via curette and submitted in a provided transport medium. Lebwohl noted that Castle Biosciences does not bill patients directly and is actively pursuing insurance coverage. He characterized the test as a cost-effective tool for patients and payers alike, eliminating the inefficiency of sequential biologic and oral therapy trials. "You're going right to the treatment that's going to work," he said.

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 12, 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