Q&A: Precision Medicine's Next Steps in Atopic Dermatitis, With Peter Lio, MD

Atopic dermatitis treatment continues to expand beyond injectable biologics, even as clinicians still lack tools to match patients with the right therapy up front. Response rates with current interleukin (IL)-4 and IL-13 blockade remain good but not complete, leaving a meaningful share of patients under-treated despite an increasingly crowded pipeline.

A prospective validation study of the AdvanceAD-Tx 487-gene expression profile test examined patients starting or switching systemic therapy for moderate to severe disease.¹ Among those identified with a Janus kinase (JAK) inhibitor responder profile, 45.5% achieved EASI 90 by 3 months on JAK therapy versus 8.3% on Th2-targeted treatment (P = .021), a response 3.8 times faster.

Separately, the oral STAT6 degrader KT-621 produced median STAT6 reductions of 94% in skin and 98% in blood after 4 weeks in the Phase 1b BroADen trial.² Blood IL-31 fell 54% on average, the first reported IL-31 reduction from a drug targeting the IL-4/IL-13 pathway. These findings point toward a future where clinicians choose between JAK inhibitors, biologics, and oral options based on molecular profile rather than trial and error.

For now, testing logistics and limited practice experience keep gene expression profiling from routine use, and most clinicians still personalize care empirically, starting with a biologic and layering on topical therapy as needed. Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine and founding director of the Chicago Integrative Eczema Center, tracks this pipeline closely in his atopic dermatitis practice.

In the following interview, Lio spoke with HCPLive at LEADderm 2026 in Newport Beach, California, about where precision medicine in atopic dermatitis stands today:

HCPLive: What drugs or disease states with new data or PDUFA dates excite you?

Peter Lio, MD: There's a tremendous amount happening in dermatology. My focus is generally on atopic dermatitis, and there are several exciting drugs and new developments happening. We've seen some programs shift. A couple of drugs, particularly in the OX40 pathway for atopic dermatitis, have been dropped, which is interesting in itself, to see pathways that maybe aren't positive. But the one I'm excited about is an oral agent coming for atopic dermatitis. It's still fairly early on, but what's exciting is it's an oral pathway similar to the IL-4 and IL-13 blockades, but taken orally, and it seems to be highly effective.

There are also some new topicals in early phases, including a topical botanical agent for atopic dermatitis that I'm particularly excited about, because a lot of my patients want something more natural. It has antimicrobial effects as well as anti-inflammatory effects. I think we're finally beginning to see enough choices to start having precision medicine discussions. We also have a new lab test that can help decide between a JAK inhibitor and a more Th2-focused biologic, whether a patient is a better candidate for one or the other. I'd argue it's not quite ready for primetime, at least in my practice. I don't know how to use it yet, but it's an amazing first step.

This is exactly the kind of groundwork where, instead of just guessing, we're able to get a sense of somebody from a skin scraping or a swab and say this pathway is going to be good for you, or this pathway might not be good for you, you're more likely to have a side effect or an issue and it's not going to work. All of those pieces we're hopefully going to be able to predict and have that precision and personalized medicine, which has always been the goal, but we just haven't had the tools until now.

HCPLive: Can you describe the test, and how close are we to true precision medicine?

Peter Lio, MD: I think the precision medicine journey is something that will probably never hit an end point. It's going to be a continuous journey of refinement and improvement, much like the virtuous cycle of drug development: we get a new medicine, it teaches us more about the underlying disease state, and that in turn allows us to refine and get better medicines. It's a building process. Rarely do we have a breakthrough that solves the whole thing; most of what I'm involved in never works that way, it's a slow process of iteration. We're seeing that with psoriasis now. We've moved so far with psoriasis and refined it so much, though we still don't really have personalization yet.

What we've found is we have agents so good for so many people that you don't really have to personalize; you can say one of these newer agents gives a really good chance you'll be clear or almost clear very quickly. With atopic dermatitis, the numbers are good, but they're not that good, so there's still a lot of unmet need, and more testing would help. That first test is very specific and looks at one pathway. It would be nice to understand more: is this patient primarily a skin barrier problem, an inflammatory pathway issue and if so where, or somebody who might benefit from microbiome manipulation, or all of the above? The other possibility, especially with diseases like atopic dermatitis, is they're somewhat messy, so maybe we'll never fully personalize it because it's multiple components, and we'll always have to think more holistically.

Maybe great drugs will come to market, like with psoriasis, that obviate a lot of this. In other fields of medicine, particularly oncology, we've seen the biggest leaps in precision medicine, being able to understand tumor characteristics and say, you have this mutation, so this pathway is exactly what you need. That's really been the gold standard, and oncology is setting the tone for everybody else, but I don't think we're anywhere close to that yet with inflammatory conditions, which tend to be messier and, frankly, more interesting to me because of that.

We also have this whole world of over-the-counter products, which in Europe they might call dermo-cosmetics: cleansers, moisturizers, and skincare products we use often without as much data, though the science is rapidly progressing. I love being at conferences that showcase the science behind our OTCs, and I often feel we don't give them the same spotlight as drugs. Everybody focuses on a drug, but OTCs are undergoing their own renaissance, and it's been incredibly exciting to be part of that too.

HCPLive: When did you first hear about precision medicine, and how has it evolved?

Peter Lio, MD: We've always talked about and dreamed about precision medicine. In science fiction, somebody gets a body scan and knows exactly what's wrong. That's really the goal: personalizing to you what would be safe and effective, the right solution to your specific problem. We've always wanted that. We haven't had the tools, but now we're beginning to understand more of the genetics, and that's where the early work came with genetic diseases, where there was one gene, one protein, one mistake.

That opened the door, and for a minute everybody thought this is how all of medicine is going to be, we're going to solve it all. Then we quickly hit a wall: this isn't one gene, one protein, one disease. It's way more complicated, we can't find a gene mutation that's reliable, and it's different across populations and individuals. We've kind of understood some of those simpler diseases, for better or worse, and things like gene therapy are happening. But for these more complex diseases, we still have a ways to go. I hold out hope we're going to get there and understand them, even if they're multifactorial, and that's going to make it that much more satisfying when we do.

HCPLive: Is the Castle test Dr. Swanson mentioned the one you meant?

Peter Lio, MD: Yes, that Castle [Biosciences] test is the one that helps us decide between a JAK inhibitor, which is broader, and a more targeted IL-4/IL-13 biologic. It's pretty good; it gives us a sense of which patient might do better with one or the other. Ultimately, the question it answers is whether a biologic would be enough for this patient, at least as a clinician how I interpret it. Smarter people might interpret it a little differently, but when I look at it as a clinician, it's: do I think I could get by with a biologic, which has a smaller safety profile and is a little easier to use?

The answer could sometimes be no, they're unlikely to do well with a biologic, so you have to use the bigger, more encompassing medicine, the JAK inhibitor, with the safety and tolerability issues it carries as well. We have to do lab monitoring and counsel a bit more about things like blood clots. So there's a potential bonus there. For me at this point, and it may change, and I'm excited for it to change and refine, I feel the logistics of the test and its potential to help me are fairly limited in usefulness right now. So I've often said, why not start with the biologic, and we can empirically know the answer pretty quickly?

Even if it doesn't fully help, sometimes the biologic will help a bit, and then I can add other things like topicals. I'm personalizing it a little more on what we might call a diagnosis ex juvantibus: what's helping them? I customize to the patient by trial and error, on an individual basis, to see if it's going to work. But I foresee a future when I'll be able to do a simple test and say you're not a good candidate for this, let's skip right to the good stuff.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. 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. Published online February 16, 2026. doi:10.1016/j.jaad.2026.02.034.

2. Kymera Therapeutics. Kymera Therapeutics announces positive results from BroADen phase 1b clinical trial of KT-621, a first-in-class, oral STAT6 degrader, in patients with moderate to severe atopic dermatitis. Published December 8, 2025. Accessed September 10, 2026. https://investors.kymeratx.com/news-releases/news-release-details/kymera-therapeutics-announces-positive-results-broaden-phase-1b.