Emerging Therapies and Future Directions for Pediatric Atopic Dermatitis

Raj Chovatiya, MD, PhD: In the last few minutes of our discussion, I want to talk about what’s coming and future directions and hear from the experts on the panel about what we all want to see when it comes to our patients with atopic dermatitis [AD]. I’ll start by saying we spent a little time touching on crisaborole, which is a PDE-4 inhibitor, as a potential mechanism. After about 5 or so years on the market, reception has been a bit lukewarm in the sense that efficacy hasn’t necessarily been outweighed by the number of patients who experience some degree of cutaneous sensation issues, whether it’s stinging, burning, or whatnot. For a while there was a thought about whether PDE-4 is the right target for atopic dermatitis. Is there something else we should be thinking about?

There’s been a bit of a flurry of activity with a couple of medications. There’s roflumilast and difamilast, both of which are moving through clinical trials that are showing that PDE-4 inhibition might be a reasonable and good strategy for patients with atopic dermatitis. You can potentially get even better efficacy than we saw with crisaborole, and we can also see good vehicle technology and drug technology minimizing any adverse events we thought about related to cutaneous sensation. Those are the 2 that I’m particularly excited about, especially since roflumilast is moving its way through psoriasis…in addition to atopic dermatitis. That’s going to be really exciting for all of us.

But I’ll ask you guys. Maybe we can start with Brit and then Peter. How do you anticipate the treatment landscape of atopic dermatitis going forward? Is there anything that you have your eye on that you think is going to be big? Is there something you want to see that you’re not seeing in the development landscape?

Brittany G. Craiglow, MD: More topical medications will be welcome. Personally, I’m hoping to see a younger indication for oral JAK [janus kinase] inhibitors for AD because I do think there’s a role in a younger population. There aren’t going to be a ton of kids, but we still have kids for whom dupilumab isn’t quite cutting it or the injections are so traumatic that they fall off. For me, that’s probably the most exciting thing.

I mentioned this briefly earlier, but a lot of these kids have comorbidities like alopecia areata. About 30% of patients with alopecia areata also have atopic dermatitis. We know that JAK inhibitors are useful for both diseases, so just as we’re getting asthma and AD with dupilumab, we may be able to capture multiple comorbidities with oral JAKs in younger patients too, which will be really exciting.

The more options we have, the better. It will be interesting to see in 5 or 10 years. We don’t really have biomarkers. We don’t really have ways to say if you’ll probably respond better to this medicine or that 1 because everybody is a little different. I have patients on an oral JAK inhibitor for alopecia areata whose eczema doesn’t get much better. There are different phenotypes, probably related to different genotypes, and different things going on. We may be able to personalize our drugs a little better down the road. That’s more pie in the sky. [Right now we] try this, if it doesn’t work then we try that. Maybe we’re going to be able to say, “You have these characteristics, so this medicine might make more sense for you.” That’s going to keep it interesting.

Raj Chovatiya, MD, PhD: I love it. If Peter gets to insert his hot take, then I get to insert mine. I don’t know if we’ll necessarily get to one of these biomarkers and say these 3 or 4 things [will work], given the heterogeneity of the disease. Maybe it’s going to be dependent on more patient-reported, patient-intrinsic factors. When they tell us these different things about their disease, that’s how we’re going to choose, as opposed to whatever the genes in the serum say. But that’s a different discussion for a different time. Peter, what do you have your eye on? What’s exciting to you or interesting? What do you want to see happen that’s not happening?

Peter A. Lio, MD: There are a couple things. Definitely, selfishly, we love these powerful systemic agents because those are the patients we see who are miserable and suffering and out of options. But from a population standpoint, I’m excited about the topical nonsteroidal medications as well. Roflumilast and difamilast—those are exciting. With tapinarof, which is the aryl hydrocarbon receptor inhibitor, I’m interested in what they’re doing because it’s approved for psoriasis already. They already have data in atopic dermatitis suggesting remission. This is my favorite buzzword, and I want to see how that’s going to play out. I’m also interested in the microbiome. The microbiome is the final frontier. We’re outnumbered by the microbiota on our skin and in our gut. What we find in prebiotics, probiotics, synbiotics, are there going to be things that we can do?

There are a number of companies working on some neat things, including OTCs [over-the-counter medicine]. The OTC space is blowing up. Unfortunately, we don’t have the same level of evidence and regulation. From new things like topical anti-staph treatments, which use endolysins derived from bacteriophages, to pro and prebiotics, it’s amazing. It’s hard to keep up with. The level of evidence is lower, but these can sometimes have an outsize effect on patients at large because if we can prevent them from getting to the point where they need us then everybody wins.

Transcript edited for clarity