Precision Medicine Arrives in Atopic Dermatitis: Guiding Systemic Treatment Decisions Through Gene Expression Profiling

We all have had that patient with moderate to severe atopic dermatitis (AD)—the one who has tried everything. They have rotated through topical therapies, phototherapy, and perhaps 1 or 2 systemic agents. The patient improved temporarily on a biologic, only to flare again months later. Or maybe they never reached satisfactory control at all. As dermatologists, we know this pattern all too well: Choose a therapy, hope it works, and wait to see how the patient responds.

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.

An Important Unmet Need in Clinical Dermatology

AD affects approximately 26 million people in the United States, with about 40% of those 12 years and older having moderate to severe disease.^1,2 Among these patients, the burden is substantial: More than half report inadequate disease control, and over 60% describe their itch as severe or unbearable.¹ Many have already exhausted topical options and are ready to start, or switch, to systemic therapy. Yet deciding whether to begin with a Th2-targeted biologic, or a Janus kinase (JAK) inhibitor that impacts multiple inflammatory pathways, often involves educated guessing.

This lack of precision can prolong disease activity and create frustration for patients and clinicians. Approximately 40% of patients who start taking a Th2-targeted biologic eventually need to add another therapy or switch.³ For individuals already struggling with itching, flares, sleep loss, and psychosocial stress, each ineffective treatment delays meaningful relief.

Exploring the Biology Behind Treatment Response

As one of the investigators involved in the clinical research that led to the development of a new molecular tool for AD, I have seen how understanding immune biology can transform the way we choose therapy. The work began with a simple question: Can we better characterize biological variability to improve the selection of systemic therapies?

Through this research, our team identified immune patterns that distinguish patients more likely to respond to one therapy class over another. These findings were foundational to the development of AdvanceAD-Tx, a laboratory-developed test that measures the expression of 487 genes across 12 skin biology and inflammatory pathways.

Using a quick, noninvasive skin scraping (no biopsy required), the test applies machine-learning algorithms to classify patients into one of 2 profiles:

• A JAK inhibitor responder profile
• A Th2 molecular profile

These profiles help match the molecular biology underlying each patient’s disease to an appropriate therapeutic class. In practice, this information can complement clinical assessment, adding an objective dimension to the traditional reliance on selecting a therapy, observing the response, and adjusting over time.

Insights From the IDENTITY Study

The development of AdvanceAD-Tx was grounded in data from IDENTITY, which was a prospective, multicenter validation study conducted across 49 US clinical sites, sponsored by Castle Biosciences, Inc. The study enrolled patients with AD, including those new to systemic therapy and those considering a switch.

In the study, patients with a JAK inhibitor responder profile who were treated with a JAK inhibitor achieved markedly better outcomes than those treated with a Th2-targeted biologic.

By 3 months, these patients were significantly more likely to:

• Achieve a 90% or greater improvement in Eczema Area and Severity Index (EASI) 90 score at a 3.8 times faster rate
• Report no itch
• Remain flare free

These findings highlight how aligning treatment with a patient’s disease biology can reduce therapeutic cycling and accelerate disease improvement.

Applying Molecular Insights in Practice

The strength of this test lies in its simplicity and practicality. Samples are collected through a quick, in-office scrape of a patient’s lesion, and the molecular data can complement clinical observations.

For patients with a JAK inhibitor responder profile, this result can provide confidence in initiating a JAK inhibitor rather than a biologic that is less aligned with their disease drivers.

For patients with a Th2 molecular profile, outcomes are similar for both classes of therapy, allowing us to weigh safety, dosing preference, or cost in shared decision-making.

AdvanceAD-Tx can add a new dimension to our treatment strategy and approach, bringing greater clarity and confidence to systemic treatment selection.

Evolving Toward Precision Dermatology

Molecular guidance has the potential to redefine how we manage AD, tailoring therapy based on each person’s immune profile. This approach may allow faster symptom relief, fewer treatment failures, and less burden on patients and the health care system.

For patients, this is not just about disease control; it is about restoring comfort, confidence, and quality of life.

Providing a More Confident Path Forward

AD has always challenged us clinicians with its variability and persistence. 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 the biology beneath it. That’s the promise of molecular insight, and it marks an exciting new era for care in AD.

Aaron Farberg, MD, is a double board–certified dermatologist and Mohs surgeon; chief medical officer at Bare Dermatology in Dallas, Texas; investigator in the clinical research that led to the development of AdvanceAD-Tx; and Dermatology Times’ editor in chief emeritus (spring 2024).

References

1. Eczema stats. National Eczema Association. Accessed November 18, 2025. https://nationaleczema.org/eczema-facts/
2. Chiesa Fuxench ZC, Block JK, Boguniewicz M, et al. Atopic dermatitis in America study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol. 2019;139(3):583-590. doi:10.1016/j.jid.2018.08.028
3. Schlosser AR, Nijman L, Schappin R, Nijsten TEC, Hijnen D. Long-term outcomes of new systemic agents in atopic dermatitis: drug survival analyses and treatment patterns in daily practice. Acta Derm Venereol. 2025;105:adv41504. doi:10.2340/actadv.v105.41504