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Jason Hawkes, MD, explains how new biologics and targeted therapies are advancing precision medicine and improving personalized care in atopic dermatitis.
As the dramatic expansion of the treatment landscape for atopic dermatitis has continued in recent years, more and more targeted biologics and small-molecule medications have been providing clinicians with additional options in the armamentarium for patients with eczema.
Beyond broadening the therapeutic armamentarium, such advances in the atopic dermatitis space are also providing new insights into the underlying biology of the inflammatory skin disease, helping researchers better comprehend why patients respond differently to various drugs. In his on-site interview with HCPLive at the Revolutionizing Atopic Dermatitis (RAD) Conference in Nashville, Tennessee, Jason Hawkes, MD, professor of dermatology at the University of California, Davis, touched on the ways in which the growing number of available therapies are shaping the future of precision medicine in dermatology.1,2
In the following written Q&A interview, Hawkes explains why clinicians are learning more than ever about the distinctions between inflammatory pathways, about disease heterogeneity, and about the ways in which these discoveries may eventually lead to more personalized care:
Hawkes: Historically, we had type 2 inflammation, but we had really a single product in atopic dermatitis. Then we started dissecting out the layers. We had the first therapy, obviously, blocking one receptor, blocking multiple cytokines. Then we started seeing the development of new therapies where we're blocking just a single cytokine with IL-13. We then had IL-31 receptor, but then we kind of went backwards a little bit in terms of blockade, with the JAK inhibitors being a little less specific, more selective for a particular enzyme, but hitting multiple pathways.
What that's allowed us to do is then compare and contrast responses. Why do some people respond to these therapies for atopic dermatitis, but only certain therapies work in urticaria or nasal polyps, for example? We're just now scratching that surface. Initially, we weren't sure what other pathways were coming, but now that we have these individual products, we can start to see the pros and cons of each of them. They're all going to have a place. We are now testing in humans, rather than in cell cultures or mouse models; we're seeing the benefits. We're seeing the drawbacks of different products, and that's allowing us to get closer to personalized medicine, where we can start to tailor the therapies to the patient in front of us. That's important.
Hawkes: I think we've started to see the differentiation, where we're seeing this unique role for IL-4 in picking up some of the differentiation of the T cells, some of these autoantibodies, playing a role in unique diseases that we wouldn't necessarily have thought type 2 would have played a role. Things like chronic spontaneous urticaria and bullous pemphigoid. On the other spectrum, we have really an itch-centric therapy with blockade of the IL-31 receptor, and then we're seeing within the IL-13 space really this development of expertise in controlling atopic inflammation. We're seeing the benefits of extended dosing with these therapies that do a really good job at shutting down IL-13 in the tissues.
This has really been kind of helping us understand, again, where do we put these different products? Also, what are they teaching us? When we have a patient who initially responds and then stops responding, what does that mean? What happens if someone's inflammation gets better, but their itch persists, or vice versa? We hit their itch, and you see different changes. I think this has given us a chance to really explore this heterogeneous group. We've talked about atopic dermatitis, but there are probably these subsets within that bucket. Now we're starting to tease them out, and it's giving clinicians insight into what they saw in the clinic, which is this heterogeneity. I think it's going to help us eventually find the best treatment for the right patients.
Hawkes: I think when we talk to patients, you hear these patients talk about type 2 inflammation. They're not saying those words, but they're saying, ‘I grew up, and I developed allergies as a kid, and I had exercise-induced asthma,’ and then ‘In college I started developing this rash and the flexural.’ They're telling you a story, and I think for a lot of clinicians that's natural to say, ‘I'm hearing this flavor of type 2 inflammation.’ In our urticaria patients, they start talking about [someone having] celiac disease, and say, ‘I develop hypothyroidism and have multiple food or drug allergies.’ So we start to hear those stories. I don't think we knew what to do with that information.
We just kind of categorize these patients as being, you know, atopics. We say that all the time. We're having atopy, and I think that that's been an evolution for us to kind of start to hear that story. But now we can start to attach it, you know, to particular therapies, and that's advancing care. The issue has been the system as really applying a one-size-fits-all, or you think about the prior authorization process where it's a formulary has been selected maybe based on cost that you know you have to go through this drug that's you know inexpensive or you know we've decided that this therapy's first line before you can get to the second or third line option, and those are counterintuitive because that one size fits all is the antithesis of personalized medicine.
To have an insurance company or a healthcare system say, ‘You have to use this drug’ really takes away the ability for the doctor to say, ‘I'm hearing this story.’ And I think they're actually going to do better on this type of therapy. But you may not be able to access it. I think we're fortunate in the US, where we have copay programs and samples, and we have access as a community to get medications that we think are the right fit. But we really haven't had a lot of science backing up why I choose therapy A, but my colleague might choose therapy B, or someone else might choose therapy C. We need some metrics or measures or testing that can help us better select therapies at the outset that have a higher likelihood of working because we just want to get those patients better. We're in a try-and-fail system, and we don't always know they can look like they're going to respond and not respond.
Hawkes: Yeah, here there's an article that's years old now, but still is relevant, which shows that when you look at the burden of prior authorizations, it's had a disproportionate impact on dermatologists. That was a paper that came out of the University of Utah. It was a well-done paper that highlights the issue, which is that across all of medicine, prior authorizations are creating an administrative burden. They don't bring in revenue for practices, but they take a lot of time. I think dermatologists have we're fortunate to have a lot of these targeted, selective therapies, but they're expensive. So how do we contain costs? Also, [how do we] not make this burden really affect those practices or trying to help patients?
I think there's a fair balance, but it's often used as a stall tactic as well. It's really hard to want to put a patient on, say, methotrexate, knowing that it's a very inexpensive medication. Knowing the drawbacks and limitations of using these therapies long term. Knowing these patients have chronic conditions. I see the rationale behind having some system in place to not be a free-for-all, but I think it has ultimately restricted the personalized care that experts can offer these that really have the expertise…We would like to really have some research and data guiding some of those decisions. I think that process has started in the research area to try to get us closer to making those better-informed decisions.
Hawkes: Urticaria has been a really fun area to work in. It's probably more common. We in dermatology don't see it as much because a lot of the allergists have managed urticaria for a lot of years. But when you start to talk to people, almost every day, we talk to individuals saying, ‘I had a bout of urticaria.’ Literally at this meeting, I talked to somebody who was saying, ‘I grew up and had many bouts of urticaria,’ so we know that that's probably a little bit more common. These patients with chronic urticaria often end up suffering in silence, and they're trying over-the-counter medications. They're trying to look at what the causes might be.
I think we saw that with atopic dermatitis as well. I think that's a condition still within atopic dermatitis. I still think there are a lot more patients out there that have it. We see a small proportion of patients as a specialty. There's been a lot of data that these patients are out there in primary care or with their general practitioners that haven't been formally diagnosed. HS is another condition where we see a lot of underdiagnosis. But I think in the type 2 conditions, urticaria comes up. I think asthma is often underrecognized, especially for those that maybe have very mild asthma. Allergic rhinitis, we know, is very common. I think that's been, you know, appreciated. And when you start talking to patients, you hear that story.
Hawkes: One area I mentioned, sort of in in our in our panel, is how do we induce remission? One really interesting component for patients living with atopic dermatitis is that there's a subset of patients who just grow out of their disease. We don't really understand that process, and that's a really important mechanism to try to understand. We see that in other disease states, so guttate psoriasis, for example, one of those acute eruptive forms of psoriasis. But we know those patients have a risk of developing chronic plaque psoriasis. But most of them are self-limiting. So, what is it that's different in gut-based psoriasis than chronic plaque psoriasis? What's different in these patients that outgrow their disease as opposed to those that have persistent disease well into adulthood?
I think if we could uncover some of those mechanisms, what's the immune system doing? Maybe it's genetic. What's happening to corral that immune response to, you know, shut it off, regulate it, so that we don't have this, you know, persistent, chronic, active disease. That's an area where it's the silver bullet. We're all looking for ways to turn off disease, but I think that's really important for these chronic conditions. These patients want to stop living with their disease. They don't want to be on therapies, and I think obviously that move towards a cure, right, or remission, finding ways to really put disease in remission.
Disclosures: Hawkes has served as a consultant, advisory board member, investigator, and speaker for multiple pharmaceutical companies involved in dermatology, including AbbVie, Arcutis, Blueprint Medicines, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Regeneron, Sanofi, Sun Pharma, Takeda, and UCB, among others. He has also received research funding and reports stock ownership in Regeneron.
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