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Addressing atopic dermatitis with IL13 inhibition
Evidence-Based Care in Atopic Dermatitis: IL-13 Inhibitors to Treat Moderate to Severe Disease

Released: June 25, 2025

Andrew F. Alexis
Andrew F. Alexis, MD, MPH
Daniel Butler
Daniel Butler, MD
Shawn G. Kwatra
Shawn G. Kwatra, MD
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In this episode, Andrew F. Alexis, MD, MPH; Daniel C. Butler, MD; and Shawn G. Kwatra, MD, discuss IL-13 inhibition for treating patients with moderate to severe atopic dermatitis (AD), including:

  • The available biologic therapies that specifically target IL-13
  • Where these agents fall in the 2024 American Academy of Dermatology treatment algorithm
  • How these agents compare to other AD therapies like topical corticosteroids and oral JAK inhibitors
  • A detailed patient case to highlight take home points

We are going to talk about IL-13 inhibitors in your more significantly affected patients. This is that moderate to severe category of patients which reflects over two million people in the United States alone.

Let us move forward with this.

When you are thinking of these moderate to severe patients, 10 years ago this did not exist. We did not really know it scientifically, nor did we have all these wonderful treatments.

You have:

  • Dupilumab;
  • Lebrikizumab;
  • Tralokinumab;
  • Nemolizumab.

Those are your biologics that are FDA approved for atopic dermatitis.

Then:

  • Baricitinib;
  • Abrocitinib;
  • Upadacitinib.

Those are your JAK inhibitors that are also available for atopic dermatitis. Baricitinib not being available in the United States. But this is pretty wonderful to be able to have this.

Then to have even better than just the medications is a sophisticated understanding of the pathophysiology. You are seeing the ability for us to target some of these key players, chiefly IL-4, 13 and IL-31.

We can do this in different ways, like dupilumab can do it through blocking the IL-4 receptor alpha subunit, which blocks IL-4 and 13, whereas we have specific IL-13 blockers with lebrikizumab and tralokinumab, which are direct cytokine blockers. Then the last one is nemolizumab, which blocks IL-31 via its receptor, the IL-31 receptor alpha subunit.

So long story short, we have all these different ways of targeting this sophisticated pathway that contributes to the disease of many of our patients, and that is a really exciting place for us to be.

I am going to ask our patient case with Mark to help us understand it.

Mark is a 42-year-old man. He has a story that we have heard many times, persistent symptoms despite therapy. He has refractory moderate to severe AD despite topical corticosteroids, emollients and even intermittent systemic corticosteroids which are used everywhere. He reports intense pruritus, widespread lesions. He describes his quality of life as poor, with emotional distress and frustration.

Again, this is nothing new for anyone who sees AD patients and really patients across the moderate to severe derm spectrum in general. His past medical history is that he has had atopic dermatitis since he was a child. It is now progressed to that moderate to severe category, which is not unusual in adults. He has a history of seasonal allergies and asthma. So this is just a slam dunk atopic patient.

His physical exam shows widespread erythematous and lichenified plaques of the arms, trunk and legs. He has areas of excoriations basically all over with no signs of active infection, which is great. This is easily someone that we can target.

Stark erythema, that really red color in that moderate to severe category. Of course, that there is a huge body surface area involved here, which usually means major quality of life impairment.

Let us go into some of the guidelines. So the AAD, the American Academy of Dermatology published their guidelines in 2024, which is interesting because it seems like it was very recent, but we have had a lot of progression since then. Specifically looking at systemic therapies for moderate to severe patients.

The general recommendation is for a first-line therapy for moderate to severe patients is to include biologics. Now the interesting piece of this is in 2024 we only had two of the possible now available biologics. We had dupilumab and tralokinumab, but we now have added lebrikizumab and nemolizumab to that group. We really consider that that moderate to severe first-line therapy should be the biologic step first.

I want to go over some of the differences between the biologics. We already talked little bit about their classifications, meaning what they target specifically. I would love for us to also go over some of the nuances for their approval. For example, dupilumab is approved for those over six months of age, while the other biologics are approved for those over 12 years of age. They are all given subcutaneously.

There are slight variations in some of the dosing for the pediatric patients, but for the most part, it is pretty straightforward for all of them. Then the other thing to note is the availability of extended dosing for both tralokinumab and lebrikizumab, your IL-13 agents, which can after a certain amount of time, typically about 16 weeks, you can extend them out to Q4 week dosing, which is really nice.

Nemolizumab is always Q4 week dosing, whereas dupilumab is Q2 week dosing. Then there is also the warnings or the side effects of the medications. The IL-4 and 13 in biologics have a shared side effect profile, which is predominantly conjunctivitis and a very small concern for parasitic infections, whereas nemolizumab, the recommendation is just for avoiding live vaccine specifically. But I think we are all lucky because we can really put these in the category of very safe medications.

Let’s dive into those AAD guidelines a little bit more. Mor generally the treatment algorithm for AD. It is not surprising to see that for mild patients, you are really starting with your topical regimens, your stronghold historical treatments like topical corticosteroids and then topical calcineurin inhibitors, PDE-4 inhibitors. We have others now that are available. Then of course emollients making sure someone is well hydrated.

But for that moderate patient the main thing is seeing that the AAD guidelines really do recommend stepping into that biologic world right off the bat. If those biologics are not quite working, then you could possibly go into some of those more significant JAK inhibitor medications, which are still very effective and very predictable with all the studies that have been done. It is really nice to have them as backup options.

Then for long term management, you are probably using a balance of still the topical medications with a more systemic option for the patients for their consistent treatment, not just for breakthroughs.

When we look at the comparative data between all the biologics and all the systemic agents out there, we can do something called a network meta-analysis. It is really nice to have this, although I do want to make sure that we are cautious interpreting everything because each one of these is created off of different studies. Each study is a little bit unique.

These are not a true head-to-head comparison where you are using the medications in the exact same environment. We always have to take a little bit of a step back when we are looking at this. But I think it is truly helpful to see certainly how many really effective treatment options we have out there. Then we can glean some comparative efficacy from these network meta-analyses.

If we are looking at this specific biologics, in this network meta-analysis, the top effective biologic is lebrikizumab. That is certainly for EASI-75. This is as compared to Dupixent as well as trailokinumab in there. Then for some of the data there for EASI-90, where the biologics are very similar. Dupilumab, a little bit higher, but lebrikizumab and tralokinumab very close behind with still a significant amount of patients, almost one in five patients who are getting EASI-90, which for those who are not familiar with the EASI score, is a clinical score that shows the improvement of 90% of eczema on someone's skin.

This is pretty impressive. Of course, a lot of those JAK inhibitors that are really, really effective right off the bat. I think that is important to point out. But those first-line biologics are still really effective. When you are looking at that pretest question that we talked about two of those IL-13 inhibitors right there in front of you, which are showing really great efficacy, both an EASI-75. A 75% improvement and EASI-90, so a 90% improvement.

All in all, very impressive.

Let us discuss. I am going to pull on a couple of my colleagues, Dr. Alexis and Dr. Kwatra for some of these questions. There is one that I really want to touch on here. But let us go over the questions first.

Based on the clinical guidelines, what are the key advantages of biologic therapies, such as IL-13 inhibitors, over systemic corticosteroids in treating moderate to severe AD?

That is really the question I want to harp on. The reason being is that a lot of people, systemic corticosteroids was what they used for ever, before we had this glut of options. Now that we have this, I want to dive into why the AAD would be making those recommendations to use these biologics as first-line for those moderate to severe patients.

Dr. Alexis, what do you see as some of the benefits of using biologics as opposed to systemic corticosteroids for your moderate to severe patients?

Dr. Alexis: Yes. Dan, I see so many advantages to using a targeted biologic therapy, like an IL-13 inhibitor over systemic corticosteroids in treating moderate to severe AD as well as topical corticosteroids. With systemic corticosteroids, we are all familiar with the potential side effects of systemic corticosteroids, including, adrenal suppression and other less common things like avascular necrosis of the femoral head and so on. The list goes on.

But even moving from side effects and just talking about effective control of this chronic condition, this chronic immune-mediated condition, moderate to severe AD, when we use corticosteroids for short periods of time to just treat flares. We are essentially just putting out fires. The patients experience is like a roller coaster ride, where they come in flaring and miserable and then maybe get some short-term relief with a two, three week course of corticosteroids and then are fine for a little bit, but only for the next flare to occur down the line.

That historically has been a very frustrating and not a great way to function as an atopic dermatitis patient. Not to mention the safety concerns of having to be on corticosteroids frequently or for prolonged periods.

Meanwhile, let us contrast that with targeted therapy like IL-13 biologic. You are able to achieve longitudinal control of this and give that patient like a smooth long-term trajectory = where flares are rare and minimal in severity as compared to the alternative.

Dr. Butler: Yeah. I mean that is a bag of pearls there for everybody listening. Dr. Alexis is an excellent educator and you can totally see there why. Well, thank you for that, Dr. Alexis. I totally agree. I am going to pass it to Dr. Kwatra as well to talk a bit about systemic corticosteroids. Then the second part of this question here is how do you also make that comparison with the oft used topical steroids as well. What would be the benefit in a patient who has perhaps historically used only topical steroids and then intermittent systemic steroids?

Dr. Kwatra, how do you have that conversation with the patient about the potential of using an IL-13 targeted biologic versus this historic use of just steroids topically and systemically?

Dr. Shawn Kwatra (University of Maryland School of Medicine): Yeah. Dan, thanks. It is a great question. I love the way you and Andrew think about it. I think we need to have a paradigm shift about what these medications really are because people think, okay, topical steroids, this is a shot versus an oral pill. Ultimately people sometimes mistakenly think that a shot must be more dangerous, but that really could not be further from the truth.

What I try to impress upon folks is that this is a very specific, tailored treatment to one thing. It is just one thing, IL-13, the major mediator. All the biomarker studies show IL-13 is dysregulated the most. This is the master conductor of your disease. Why should we have this non-specific approach both topically or via oral steroids when we know that those steroids affect so many other cytokines and have so many local and systemic side effects. That is a big consideration is educating. It is not just a cream or an ointment versus a pill versus a shot. It is what is in it.

I 100% believe an IL-13 target inhibitor is way safer than an oral steroid, a topical steroid. It just is safer. These diseases where you have chronic itching or other symptoms like that, there have been studies showing that even at a minimal amount, an itch of three to five on a 10-point scale, you have systemic inflammation in your whole body.

I think the second part of this is if you are having symptoms, especially that are not amenable to current therapies, you actually are having more likelihood of developing other comorbidities and other problems. I always talk about the price of not treating.

When you treat, you want to treat with a really tailored, therapeutic agent. I think we just need that paradigm shift reinforcing it. A shot is not worse than a pill versus a cream. It is what is in it. I think we are we are peeling it back and we are getting down to the science and the mechanism, like, you guys did such a great job. I think that is starting to emerge.

Dr. Butler: Absolutely. I love that. My takeaway points from that are a paradigm shift and the cost of not treating or partial treating, which is what I think we are doing if we are just giving systemic corticosteroids and temporizing with topical steroids.

Thank you both for your pearls there.

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