Genomic Insights and the Future of Personalized Care in Atopic Dermatitis

Aaron Farberg, MD, discusses how emerging genomic tools, including the Advanced ADTX test, may help identify distinct molecular profiles in patients with atopic dermatitis and guide more personalized treatment selection. He highlighted the potential for gene expression profiling to reduce trial-and-error prescribing while emphasizing the need for broader insurance coverage, clinical guideline integration, additional real-world evidence, and clinician education to support routine adoption.

Transcript

Hi, I'm Dr Aaron Farberg, a board-certified dermatologist based in Dallas, Texas. I have a large private practice, Bare Dermatology, and also help lead a dermatology residency program at Lake Granbury Medical Center.

How are emerging genomic insights improving our understanding of atopic dermatitis and the factors that contribute to differences in disease presentation among patients?

Dr Farberg: So, as dermatologists, we have historically viewed atopic dermatitis primarily through our eyes, through the clinical lens. We rely on what we see on the surface, like erythema, excoriations, and lichenification. However, emerging genomic insights are completely changing that paradigm.

Tools like the Advanced ADTX test show us that diseases that otherwise appear visually identical in their clinical presentation are actually driven by vastly different, heterogeneous molecular components beneath the skin.

And that's right, I said everyone's favorite word, heterogeneity, but now we can actually explain it by looking at people's gene expression.

So, we utilize a simple, noninvasive skin scraping. We all do this as dermatologists. We scrape the skin for fungus, and now we can do it for this testing. We can evaluate that patient's RNA expression, looking at 487 specific genes across 12 different pathways.

We can finally essentially peer under the hood of this disease, and of a lot of inflammatory diseases, but we're talking about atopic dermatitis.

And what we've discovered is that patients have completely unique immunologic drivers. In other words, there are patients who have more of a Th2 profile driving their disease, and in others, it's broader.

Now, this genomic data really explains why 2 patients who otherwise may have the exact same clinical severity or Eczema Area and Severity Index (EASI) scores, if you're in studies, will have wildly different disease trajectories. Essentially, they're going to respond differently to different therapies.

We're finally moving past this purely morphologic understanding of atopic dermatitis, and we're getting to this highly precise molecular understanding, which is really the foundation, or the next step, toward true precision medicine, in my opinion.

What role could genomic information play in personalizing treatment selection for patients with atopic dermatitis?

Dr Farberg: So, currently, when we move a patient from topical therapy to systemic therapy, we're relying on the ever-well-known, frustrating trial-and-error approach.

And this leads, obviously, to a lot of treatment cycling. We have immense patient frustration. Let's not forget about them. They're sitting there trying a drug and hoping that it works, and all they've got to do is wait and see.

And, of course, that leads to unnecessary health care costs as they wait weeks and months to see if this biologic injection or an oral small molecule is actually going to work.

Now, genomic information can completely revolutionize this by acting as a biological GPS in helping us guide treatment selection.

So, by using gene expression profiling with the Advanced ADTX test, we can classify our patients right on the spot, right at the point of care, into 2 distinct molecular signatures.

One of them is a JAK inhibitor responder profile, and the other is a Th2 molecular profile.

Now, if a patient's genomic profile flags them as a JAK inhibitor responder, what does that mean? Well, prospective clinical data show that if you align that patient with their therapy, they're more likely to achieve faster and deeper skin clearance. It happens more quickly when you're giving them the JAK inhibitor and they're molecularly aligned.

I love that new term.

So, here we can confidently match the specific mechanisms of a patient's underlying disease with the exact therapy that will fit them, essentially bypassing all the trial-and-error guesswork that we've been doing for all these years.

What challenges need to be addressed before genomic testing or genomic-based approaches can be routinely incorporated into atopic dermatitis care?

Dr Farberg: What are the challenges? Well, while the science is incredibly exciting and it's already here, there are obviously going to be a lot of hurdles to overcome.

First and foremost, we need to get broad coverage from insurance companies. They're not ever going to want to pay for anything, especially if it's good.

And this is an opportunity to really get the right drugs, the right therapies, into the right patients' hands. So, they should want to pay for this. As patients and their customers, we should be demanding it.

Second, we also need to see these molecular tools formally integrated into the clinical guidelines. I'm on the board of the AAD's guidelines, and so we want to see these guidelines turn over a little bit faster so they can stay current with what we're all doing.

And third, we need to continue gathering long-term, real-world evidence in diverse patient populations.

We want to see more studies. Now, again, is that a reason not to get the first 2 items? No. We have data, we have studies, and there's lots of evidence. We should be able to move forward, but as good lifelong learners, we always want to see more.

And hopefully, we can even take this result from the test and apply it to even more specific therapies instead of an entire drug class.

And then finally, there's always a learning curve with any new tool or item out there to get doctors to adopt all these new things. There's a little bit of inertia there, for good reasons. So, we've got to get our peers coming along here.

As dermatologists, of course, we're highly visual, so I think there's a need for a lot more peer-to-peer education on how you can integrate RNA expression, essentially peering under that hood, into our current everyday treatments.

So, again, in my opinion, the Advanced ADTX test is already setting the standard for providing the best precision medicine for our atopic dermatitis patients today.