MOA FYI: Where Do Emerging AD and PsO Treatments Fit?

There are potential new treatments emerging in 2026 for the treatment of atopic dermatitis and psoriasis. How do these treatments work and where will they fit into the treatment landscape? Jennifer Soung, MD gives an overview. Plus, Andrea Nguyen, DMSc, MPAS, PA-C provides an update on CSU treatment and Sandri Johnson, MSN, FNP-BC, DCNP and Alexa Hetzel, DMSc, PA-C celebrate the popularity of the dermatology specialty.

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Transcript

Transcript is provided as a courtesy. It has not been edited for accuracy.

Welcome to The Dermalorian Podcast from the Dermatology Education Foundation. Dermatology has become synonymous with innovation as the specialty continues to see a slew of new drug approvals each year, bringing new chemical entities into the space and providing therapeutic options for diseases that previously had no directed treatments. Our last episode took a look at some of the recent therapeutic advances in medical and cosmetic dermatology. This month, we turn our attention to the pipeline and some promising developments for the management of atopic dermatitis and psoriasis.

We'll start with atopic dermatitis, where there is growing anticipation for new OX40 agents and S1P agonists in development. DEF Biologic and Small Molecule CME Bootcamp faculty member, dermatologist Dr. Jennifer Soung, gives an overview of the current treatment landscape and talks about where these agents may fit in.

Dr. Jennifer Soung:

As a clinical researcher, I love mechanism of action because it helps me understand how we're targeting inflammation in situations where I want to combine agents. It also helps me understand the side effects. And sometimes, some people aren't interested in the mechanism of action and just want to know if it works or not. But this is another way of thinking about your different treatment options. So, you have agents that are aryl hydrocarbon receptor agonists, which is totally new and this has to do with tapinarof, the topical cream. So, it strengthens skin barrier genes. As you know, it's indicated for both atopic derm and psoriasis, so it modulates inflammation in a very different way. And actually also strengthens the barrier, which is really fascinating.

You see next, IL-25, IL-33, TSLP, these are alarmins that are activated in the skin barrier as a result of some sort of trigger. So, we're looking at a whole host of other inflammatory proteins that are along the barrier that are involved in skin infections as well. IL-4 and 13, you know have been well established in atopic dermatitis because of dupilumab, and so these are the foundation of atopic dermatitis inflammation. IL-31 is newer, it specifically is known as an itch protein, so very powerful in reducing itch.

Next, the JAK-STAT pathway has been well established, with oral JAK inhibitors now having been available or FDA approved for almost five years now. And it is an important signaling protein in many immune cells. So what you're seeing is that it's going to modulate inflammation across many different cytokines. And that's the difference or the value proposition of a JAK, which is very different from a biologic that targets one or two cytokines versus a JAK that's targeting multiple cytokines.

And then new in development is the OX40 pathway or ligand. This is a co-stimulatory ligand on activated T-cells. Most commonly, you see them on memory cells. So the idea is that perhaps we can reduce the population of memory cells so that atopic derm patients are less hyperreactive. Their immune system is less stimulated as quickly in response to the same antigens. There are several drugs that are in clinical trials, and so the idea is that perhaps that there might be a longer lasting effect by targeting the memory cells.

And then last, signaling proteins, S1P, these are important, can play a role in inhibiting proliferation and induces differentiation at the keratinocyte level. What's unique about chronic autoimmune diseases like atopic dermatitis and psoriasis, it's not the one episode or the one flare that the patient gets. They know that's going to end or eventually get better. But it's the day in, day out, where they feel like they can't manage it, they don't know when their flare is going to come up next and it comes up even when they do everything perfect. They tell you, "I moisturize every day. I do this. And I'm minimizing exposure to this. I've changed my diet all the way around and nothing is working." And that's how exasperated they are. So, I find that I can quickly get to how severe or what they want to do based on, how does it impact your life? And they'll tell you.

The other question that I love to ask that gets quickly at how severe their disease is, "Tell me what your itch is like on a scale of zero to 10." And that's something you can document quickly. I used to ask more questions like, "How does it interfere with your sleep, your daily activities?" Those are all really good things, I let the patient talk first. But the two most impactful I think are one, how does it affect your life? And sometimes they start to cry because no one has asked them that. And then the other one is asking them about their level of itch, and that's great for documenting if you need to do a prior authorization for a systemic therapy. And then at subsequent visits, you can ask, "How is your itch?" And then you can see, is it improving? Are we 50% better? Are we getting to zero or one? Because these days, we have so many great treatments. We can get patients to zero or one itch.

Host:

We'll pivot to a look at psoriasis, but first, let's get an update on some new and emerging options in the management of chronic spontaneous urticaria. Here's DEF advisory council member, physician assistant Andrea Nguyen in this episode's Dermalorian Clinical Clip.

Andrea Nguyen:

So, CSU can be fairly common. Over a million patients, it's like 1.7 million patients suffer from CSU, and it's characterized by recurrent hives with or without angioedema, again, six weeks or longer. Women tend to be more predominantly affected than men, and so we have a two to one prevalence in female to male adults. And then so, 50% of patients can go into remission within the first 12 months with or without therapy. However, primary treatment for us with oral antihistamine, second generation H1 inhibitors, a number of patients may still go on to be symptomatic as well. So, a percentage of these patients, 11% can have symptoms for over five years. That's a long time to suffer with CSU. Diagnostic delays are common. These patients are frequently not seeing us in dermatology, maybe even potentially not seeing allergy there. They can be bouncing in and out of urgent cares and even the ER.

A very, very, very new update. So, as of just September 30th, October 1st, we have remibrutinib or Rhapsido approved now for CSU, and so this is an oral agent approved again for CSU for patients who remain symptomatic despite oral antihistamine usage. So remibrutinib, it's a 25 milligram dose BID. Their phase 2B trial at week four, the UAS7 was reduced by 83% with treatment, as compared to 13% on placebo.

And then their pivotal trials we see here, we see REMIX-1, and this is looking at patients over time from week one to week two to week 12 to week 24. And we see the differentiation here between patients on active treatment with remibrutinib 25 milligrams BID at week one, already having some differentiation there from active treatment to week two to week 12 to week 24. After 24 weeks, all patients that were on placebo were switched to active treatment arm, and so you see many of those patients, they catch up week 28, week 32, week 36, getting very close to the respondents of clearance, UAS70. So basically, complete response, catching up fairly quickly to the patients who started on remibrutinib from baseline or day one.

There are many therapeutic options that are in clinical investigation for CSU. And so this is the fun thing about medicine and technology, right? So for a long period of time, sometimes we might not have any treatments, and then all of a sudden we have many treatments potentially brewing in the books. And it's really by identification of key cytokine pathways and mechanisms in our body, really looking at the MOA. And then potentially, you find these key pathways and then there's a lot of research and development investment here. So we have multiple agents, anti-IgE, mast cell depletion, JAK inhibitors, other BTK inhibitors, and other anticytokine therapies that are being investigated for CSU.

Host:

You are listening to The Dermalorian Podcast from the Dermatology Education Foundation. In the field of dermatology, an investigational oral IL-23 medication is generating buzz. According to data published so far, icotrokinra performs similarly to injectable IL-23 agents. With the most recent data showing efficacy for high-impact sites like the scalp, palms, and soles. The agent has been submitted to the FDA for review for the treatment of psoriasis.

Let's rejoin Dr. Soung for an update on psoriasis and the landscape of treatments, including the role of IL-23 inhibition.

Dr. Jennifer Soung:

The 17s and the 23s are key cytokines because the clinical data tells us we can get patients clear, almost clear, or 90% clear, to the point that the National Psoriasis Foundation, the IPC is now talking about disease remission, right?

Okay, so this is the same thing that's happening in the joints. So, before you can start or talk about treatment with your patient, the very most important thing is screen for psoriatic arthritis. I argue that you can't decide on your psoriasis treatment until you screen for psoriatic arthritis. In my personal practice, I like to use the PEST questionnaire, so that's five questions, whether you give it to the patient while they're waiting and they can check it off, or I go through it in my mind. So, I'm already looking during my full skin exam, do I see any dactylitis? So, swelling of the entire digit. Do I see any... Or I'll look at their Achilles heels tendon are palpated a little bit. The patient will tell you if they have soreness there. I'll ask about morning stiffness. Morning stiffness is unique to inflammatory arthritis. Osteoarthritis gets worse at the end of the day and feels better when you rest. Inflammatory arthritis associated with PSA feels better when you continue to move.

So, screening is so important because what's happening is that we in dermatology are catching arthritis much earlier. I think in about 10 years, rheumatologists are going to see much less psoriatic arthritis.

The data also shows that the majority of the times, 75% of the time, patients present with the skin lesions first for about seven to 10 years before that subset of 30% get psoriatic arthritis. So again, we're in the key position to help patients make that connection that the skin inflammation can sometimes affect the joints, and this is what makes it a systemic condition.

Who says you have to use drugs in the order in which they were approved? So the reason why more drugs are invented is because they're safer and better efficacy. So in terms of Stelara, I was using for a very long time because this was one of the biologics with more convenient dosing in our adolescent patients with plaque psoriasis. So, that's where it had settled in the recent years, but Tremfya or Guselkumab is now FDA approved for as young as six years old, which is huge. Even though Stelara or ustekinumab I've used for so long, the safety is so great. Parents still read the package insert, so you have to guide them through it and talk about real world evidence. And it's so nice to be able to offer one of the IL-23 drugs because the package insert along with IL-17s is just so clean. It's really simplified, made that safety discussion so much easier. In fact, all of our safety information fits on one slide these days when I'm talking to you about IL-17s and IL-23s.

Here we're looking at a summary of the IL-23s approved both for psoriasis and psoriatic arthritis. I mentioned Guselkumab is now approved as young as six years old. They also have recent data that shows not only does it help for the signs and symptoms of psoriatic arthritis, but it also prevents radiographic progression. So, they actually did further studies to really show that a 23 can be powerful to prevent that radiographic progression.

What else is new? Next, we have tildrakizumab. In my personal practice, this 23 is very useful because it's covered on the medical benefits side. So in my patients who have Medicare and don't have access to other biologics or easily access based on finances, I will use tildrakizumab because it's covered on the medical benefits side. And then I'm sure all of you know risankizumab, another highly effective IL-23. Dosing is every 12 weeks while guselkumab is every eight. I really think that after monthly dosing, it really doesn't matter. So, in certain situations now we have a little more differentiation between guselkumab and risankizumab, especially with the data for psoriatic arthritis, and as well as the approval down to the age of six years old.

Another thing I love about 17s is I have an opportunity with ixekizumab to treat with GLPs. I think that addressing the comorbidities is really, really important. This is finally an amazing opportunity for me to help the patient be healthy as a whole. So a comprehensive approach, not only addressing the inflammation in the skin and joints, but also treating their metabolic conditions. Let's be honest, treating obesity or weight is really, really hard, and GLPs have given patients another amazing tool. And what it's really shown us is that obesity or weight management is not just about willpower. It's really a metabolic condition that has a genetic component and based on biology.

Host:

For the third year in a row, nurse practitioner was rated the top healthcare job in the US, while physician associate assistant ranked number two. Wage potential, job security, and opportunities for growth are among the components that US News and World Reports uses to create its annual job rankings. For DEF Advisory Council members, the rankings are no surprise. Nurse practitioner Sandri Johnson has thoughts on why dermatology is an attractive specialty for NPs and PAs, while Physician Assistant Alexa Hetzel gives perspective on the specialty and potential misperceptions.

Sandri Johnson:

I think dermatology is such a fantastic specialty. You know we are happy people. So personality wise, it's just leads to a quality of life that we all seek out within our lifetime. So, the growth is not uncommon, right? We all want to be in that a very satisfied quality of life, well-balanced life. We also are providing a care, especially SNPs and PAs, in areas of the country where there might be a sub-served communities, etc. So we tend to branch out a lot outside of cities in serving communities that are underserved.

Alexa Hetzel:

I wish more people knew that the skin is not just the skin, it's skin deep, and so going into dermatology is not just, you're taking the easy road. There are so many things for us to understand about inflammation and inflammatory skin conditions and how all of these things initially present in the skin that we have to know and that we have to diagnose. It also is such an art and a science, because you physically see your skin. So it's not just you have high blood pressure because I read it off of the cuff. It's, I see your psoriasis, I see it's flaring, I see your eczema, I see your acne. And so, I think that really blending the art and the science of the medicine that's going to effectively clear those conditions, but then handholding our patients to make sure that they're compliant and understand why we want to treat these conditions that we are recommending treating them.

Host:

That's it for this edition of The Dermalorian Podcast from the Dermatology Education Foundation. The Dermalorian Podcast is produced for the DEF by physician resources. Get more news and updates plus information on live events and webinars anytime at dermnppa.org. Thanks for listening.