A panel of expert dermatologists comments on newly approved and traditional treatment options, addressing how they target inflammation and the pathophysiology of atopic dermatitis (AD).
Raj Chovatiya, MD, PhD: Hello, and welcome to the HCPLive® Peer Exchange titled “Personalizing Treatment Selection in Atopic Dermatitis.” My name is Dr Raj Chovatiya. I’m an assistant professor of dermatology, the director of the Center of Eczema and Itch, and the medical director of the clinical trials unit at the Northwestern University Feinberg School of Medicine in Chicago, Illinois. Joining me in this discussion are my esteemed colleagues. We have Dr Matt Zirwas, a dermatologist at Dermatologists of the Central States in Bexley Ohio, where he’s the director of clinical trials at the dermatitis center and also a clinical associate professor at the Ohio University Heritage College of Osteopathic Medicine. Welcome, Dr Zirwas.
Matthew Zirwas, MD: Hello, Raj.
Raj Chovatiya, MD, PhD: We have Dr Adelaide Hebert, a professor and the director of pediatric dermatology at UT [The University of Texas Health Science Center] McGovern Medical School in Houston, Texas. Thanks for joining us, Adelaide. We have Dr Omar Noor, the co-owner and director of Rao Dermatology with offices in New York, New Jersey, and California. He is also a faculty member at Penn Medicine. Welcome, Dr Noor. Finally, we have Dr Peter Lio, a clinical assistant professor of dermatology and pediatrics at the Northwestern University Feinberg School of Medicine in Chicago, Illinois. Glad you could join us, Peter. I’m glad everyone could join us.
In today’s discussion, we’re going to talking about some patient cases. In particular, we’re going to focus on atopic dermatitis [AD]. We’re going to home in on the best approach to find the best treatment for each patient type. That’s our holy grail, and we’re starting to have much more therapeutic innovation in this space. We’re going to talk about the pros and cons of various classes of treatments and our personal approach to monitoring and switching therapies. I look forward to a free-flowing dialogue with my colleagues. With that all in place, you’re going to hear from me a little less and the smarter people much more. Let’s get started.
In the first part of our talk, I want to review some of the development and innovation we’ve seen in the AD space in a little more than a year. This includes heavy hitters like topical ruxolitinib, injectable tralokinumab, oral abrocitinib, and new indications for dupilumab, which has been around for a few years for atopic dermatitis. I’ll start with you, Dr Lio. Give us a quick update on what’s been going on with treatments for atopic dermatitis.
Peter A. Lio, MD: It’s an incredibly exciting time in the world of atopic dermatitis. For a long time, we were in a stagnant phase, and there was a paucity of new developments. We felt a little left out because psoriasis was undergoing this incredible revolution with each new treatment better than the last. Finally, we got some stuff that’s worth getting excited about. In 2016, we had 1 of our first new agents, crisaborole, which was a nonsteroidal, topical, phosphodiesterase-4 inhibitor. In March 2017, we had our first biologic with dupilumab. It was initially indicated very narrowly but has continued to get an expansion in terms of diagnoses and age range. It’s now ages 6 months and above, which is amazing.
We then got tralokinumab, another biologic agent. This 1 specifically targets IL-13, another exciting addition to that group. Then we got topical ruxolitinib, a topical JAK inhibitor that’s powerful and impressive. It gives us a lot of options in terms of our topical regimens, particularly for steroid-sparing agents. We’ve had a limitation on that, and this opens the door. Most recently, we got 2 new oral agents. We have our 2 oral JAK inhibitors, upadacitinib and abrocitinib. These are very similar, extremely powerful agents that have been able to open the door for patients who were previously stuck.
Raj Chovatiya, MD, PhD: That’s a great way to think about it, given that there are many types of patients who might be candidates for these medications. That’s what we’re going to talk about today. Dr Noor, I’ll throw it over to you. With traditional treatments—what we had and what we’ve added—how do these work to get at inflammation and other pathologic features we think about with atopic dermatitis?
Omar Noor, MD: One thing that’s interesting with this conversion of these newer medications for AD is that initially, a lot of the information we had and the way we were moving forward was based on a background of psoriasis and biologics—we had such an explosion of options for psoriasis. From an immunological perspective, the reason we started with psoriasis is because psoriasis was simple and easy. It’s a gold mine for immunology because it was very straightforward. This is what’s going on, this is how we’re going to target it, and patients are going to get better.
The reason there was a delay with atopic dermatitis is because we’re still learning. We’re still learning what cytokines are involved and what environmental factors contribute to it. Even at this point in time, with these new medications, we’re still learning how to visually identify improvement, even from a clinical trial perspective. With these new options, we have great opportunities for our patients. But now is when we dive deeper. We have to figure out who’s going to benefit from 1 treatment vs another and how we’re going to better stratify these options.
Raj Chovatiya, MD, PhD: That’s a nice way to visualize it. In 1 sense we get too caught up with loving the specificity of these treatments. This is no exception. But in the grand scheme of things, atopic dermatitis has revealed itself to be a truly heterogeneous disease, like the homogeneity we think about with psoriasis. The development has not necessarily been a linear path of getting to end points.
In the case of many of the medications that Peter had a chance to tell us about, they all target various aspects of many shared mechanisms in patients with atopic dermatitis. But we learned a lot, for instance, about type 2 information as driven by a lot of cytokines like IL-4, IL-13, IL-31, IL-5, TSLP, and others. That’s where dupilumab and tralokinumab do their thing, in terms of targeting the shared receptor for IL-4 and IL-13 for dupilumab and IL-13 itself for tralokinumab.
In the case of the oral JAK inhibitors and even the topical JAK inhibitors, they take a slightly different step in terms of working on the signaling pathway that all these signals use. They’re able to hit multiple signals at the same time. In the case of crisaborole, that’s the 1 that targets PDE4, an important signal in a variety of lymphocytes but also in granulocytes, as it relates to inflammatory signaling. In the case of many of the newer developing medications, we’re trying to find ways to mix, match, and combine these things as well.
Transcripts edited for clarity