A 487-gene expression profile test identified patients with atopic dermatitis who were significantly more likely to respond rapidly to Janus kinase (JAK) inhibitors than to Th2-targeted biologics. The study results could support a new role for molecular diagnostics in guiding systemic therapy selection.
In a prospective, multicenter study published in the Journal of the American Academy of Dermatology, investigators developed and validated a gene expression profile (GEP) test using noninvasive skin scrapings to classify patients into two molecular subgroups: a JAK inhibitor–responder profile and a Th2 molecular profile. The goal was to move beyond the current trial-and-error approach to systemic therapy for moderate-to-severe atopic dermatitis, which does not account for underlying immune pathway differences.
The assay was built using RNA sequencing data from lesional skin and a machine learning algorithm trained to distinguish patterns associated with treatment response. Validation was performed in patients aged 12 years and older who were starting or switching systemic therapy.
Patients classified as having a JAK inhibitor–responder profile achieved higher rates of disease clearance and symptom control when treated with a JAK inhibitor compared with Th2-targeted therapy. In contrast, among those with a Th2 molecular profile, outcomes were similar with either treatment class. These findings suggest that molecular stratification can identify a subgroup with a clear therapeutic advantage for one mechanism of action.
The test uses a simple, noninvasive curette-based skin sampling method and standard RNA sequencing workflows. Samples were processed in a CLIA-certified laboratory, and the algorithm assigns patients to one of two actionable categories. This positions the assay as a potential companion diagnostic to inform systemic drug selection rather than to confirm diagnosis.
Although validation was limited to patients aged 12 years and older and newer biologics were underrepresented, the study demonstrates how transcriptomic profiling of inflamed skin can translate into clinically meaningful treatment guidance.
“Together, these results highlight how aligning systemic therapy selection with an individual patient’s molecular profile may help streamline care by reducing unnecessary treatment changes and accelerating meaningful clinical improvement,” said Rebecca Critchley-Thorne, vice president, research and development, at Castle Biosciences. “By better understanding the biology driving each patient’s disease, gene expression profiling can help clinicians move beyond non–molecularly guided prescribing and enable more confident, evidence-based decisions earlier in the treatment journey.”
Newsletters
Receive the latest pathologist news, personalities, education, and career development – weekly to your inbox.
