New Gene Test Helps Tailor Systemic Treatment for Atopic Dermatitis

New gene-expression test aims to guide systemic treatment for moderate to severe 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, discussing the clinical promise of a new diagnostic tool.

Lebwohl, a dermatologist and Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai, spoke about how Castle Biosciences’ AdvanceAD-Tx 487-gene expression profile (GEP) test may change the way clinicians choose systemic treatments for people with moderate to severe atopic dermatitis (AD) (Source: Mount Sinai interview with Mark Lebwohl, MD).

Why a test is needed now

In recent years dermatology clinics have seen more patients seeking help for eczema, in part because there are new targeted treatments available that truly help some people, and awareness about options has increased (Source: JAAD prospective validation study, Silverberg et al., 2026).

That growing demand has exposed a hard truth: even with better medicines, many people still cycle through treatments without getting consistent, lasting control of their symptoms (Source: JAAD prospective validation study, Silverberg et al., 2026).

Past and present systemic treatment options

Historically, systemic options for severe AD included therapies such as systemic corticosteroids, methotrexate, cyclosporine, and azathioprine, which often carry safety concerns that limit long-term use (Source: JAAD prospective validation study, Silverberg et al., 2026).

More recently, biologic drugs — including dupilumab, tralokinumab, lebrikizumab, and nemolizumab — have improved the safety profile for many patients and offered meaningful improvement for a large portion of people with moderate to severe disease (Source: JAAD prospective validation study, Silverberg et al., 2026).

Still, Lebwohl notes that roughly a third of patients don’t achieve adequate control with biologics alone, leaving clinicians and patients uncertain about the best next step (Source: Mount Sinai interview with Mark Lebwohl, MD).

Where oral JAK inhibitors fit

Oral JAK inhibitors are another class of systemic medications that often produce rapid and robust improvements in AD symptoms, but their use is complicated by safety concerns described in prescribing information, including increased risks of infections, certain malignancies, thrombosis, and cardiovascular events (Source: JAAD prospective validation study, Silverberg et al., 2026).

In real-world dermatology practice, Lebwohl observed that serious cardiovascular and thrombotic events have appeared uncommon in the shorter-term populations studied, though infections are seen more often (Source: Mount Sinai interview with Mark Lebwohl, MD; JAAD prospective validation study, Silverberg et al., 2026).

How the AdvanceAD-Tx 487-GEP test works

The AdvanceAD-Tx assay analyzes a molecular signature made up of 487 genes from a patient’s skin sample to produce a profile that helps predict the likelihood of response to biologic therapy versus a need for a JAK inhibitor (Source: Castle Biosciences press release, Prospective validation study in JAAD, 2026).

In practical terms, the test aims to distinguish patients who are likely to achieve meaningful control with a biologic from those who may need the broader or faster effects that JAK inhibitors can offer — allowing clinicians to make a more informed decision earlier in the treatment pathway (Source: Castle Biosciences press release, Prospective validation study in JAAD, 2026).

What the test measures and why it might matter

Gene expression profiling looks at which genes are turned on or off in inflamed skin, reflecting the underlying immune activity and molecular pathways driving a person’s disease.

Because biologics and JAK inhibitors target different parts of the immune system, a molecular snapshot from the skin can provide clues about which mechanism is most important in an individual — and therefore which class of drug is more likely to help (Source: JAAD prospective validation study, Silverberg et al., 2026).

Clinical evidence supporting the test

The clinical validation data for the 487-GEP test were published in a prospective, multicenter trial reported in the Journal of the American Academy of Dermatology (JAAD), which examined whether the test could predict treatment response in patients with moderate to severe AD (Source: JAAD prospective validation study, Silverberg et al., 2026).

According to the study and related Castle Biosciences materials, the test identified patients more likely to achieve faster and deeper responses with JAK inhibitor therapy, compared with those more likely to respond to biologic therapy (Source: Castle Biosciences press release; JAAD prospective validation study, Silverberg et al., 2026).

Lebwohl, who was an author on the JAAD validation study, described these results as meaningful because they provide objective data to guide a choice that previously depended largely on clinical judgment and trial-and-error (Source: Mount Sinai interview with Mark Lebwohl, MD; JAAD prospective validation study, Silverberg et al., 2026).

How this could change clinical practice

Lebwohl called the test “practice-changing” because it may reduce the months many patients spend cycling through therapies that only partially work before finding effective control (Source: Mount Sinai interview with Mark Lebwohl, MD).

By directing patients who are unlikely to respond to biologics toward JAK inhibitor therapy earlier, clinicians may be able to shorten the time to disease control, reduce symptom burden, limit lost productivity, and avoid repeated clinic visits driven by inadequate responses (Source: Castle Biosciences press release; JAAD prospective validation study, Silverberg et al., 2026).

For patients who are likely to respond to biologics, the test could help avoid exposing them unnecessarily to the safety considerations associated with JAK inhibitors, keeping care more tailored and potentially safer over the long term (Source: JAAD prospective validation study, Silverberg et al., 2026).

Real-world workflow considerations

Implementing a molecular test into routine care raises practical questions: how quickly results are returned, how the test is billed, and how clinicians interpret the score alongside clinical factors such as comorbidities, patient preference, and prior treatment history.

Lebwohl emphasized that the goal is to combine this objective data with clinical judgment — not to replace it — so the test becomes an additional tool to help select the best treatment from the start (Source: Mount Sinai interview with Mark Lebwohl, MD).

Safety, trade-offs, and shared decision-making

Choosing between starting a biologic or a JAK inhibitor involves weighing benefits and risks: biologics have improved long-term tolerability for many patients, while JAK inhibitors can offer faster and sometimes deeper improvement but carry boxed safety warnings that need to be considered (Source: JAAD prospective validation study, Silverberg et al., 2026).

Lebwohl pointed out that with a data-driven test, clinicians and patients can have a clearer conversation about these trade-offs, using the test result to personalize the approach and monitor safety appropriately if a JAK inhibitor is chosen (Source: Mount Sinai interview with Mark Lebwohl, MD).

What patients can expect

If a clinician orders the AdvanceAD-Tx 487-GEP test, the process typically involves obtaining a small skin sample and sending it to a specialized lab for analysis.

Patients should expect their clinician to discuss the test result in the context of their overall health, past treatments, and personal priorities — for example, whether quick symptom relief is a priority or whether minimizing certain safety risks is most important (Source: Castle Biosciences press release; JAAD prospective validation study, Silverberg et al., 2026).

Bottom line

The 487-GEP test offers a new, molecularly informed way to help decide whether a person with moderate to severe atopic dermatitis is likely to do well with a biologic or may need a JAK inhibitor to achieve meaningful disease control.

Led by clinicians such as Mark Lebwohl, early data from a prospective validation study suggest the test can meaningfully influence treatment selection and shorten the time to effective therapy for some patients, though implementation details and long-term outcomes will continue to be evaluated (Source: Mount Sinai interview with Mark Lebwohl, MD; Castle Biosciences press release; JAAD prospective validation study, Silverberg et al., 2026).

Sources

1. Castle Biosciences press release. “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.” 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 (Source: Castle Biosciences press release)
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.” Journal of the American Academy of Dermatology. 2026; S0190-9622(26)00230-6. doi:10.1016/j.jaad.2026.02.034 (Source: JAAD prospective validation study, Silverberg et al., 2026)
3. Mount Sinai Health System. Interview and commentary from Mark Lebwohl, MD, Dean for Clinical Therapeutics, Icahn School of Medicine at Mount Sinai. (Source: Mount Sinai interview with Mark Lebwohl, MD)