Matthew Zirwas, MD

We’ve had a great conversation about treating atopic dermatitis. We all see a lot of patients. What I’d like to do is ask each of you: In your practice in dealing with these patients, do you have some kernels of truth that you’ve relied on that have helped set your patients up for success, or something you can give our audience that they can take back and utilize to have the best possible outcomes? Matt, I’m going to start with you.

 Linda, I’m going to give you the spiel that I give a patient once I’ve gotten through disease education and we’re now selecting therapy. I’m a believer that setting them up for success means shared decision-making so that they’re not taking what I think they should be on, they’re taking what they think they should be on. It can be really simple. I believe that shared decision-making needs to be really simple: 2 options, at most 3 bullet points per option.

Here’s my spiel: “Luckily for you, we have great options now, they’re not steroids, you’re going to stay on them long term. I’m going to give you some choices, and you’re going to tell me which one sounds better. First, we can treat you with a pill. It’s going to start working in 2 or 3 days, but it does weaken your immune system. Or we could give you a shot that starts working in a week or two but does not weaken your immune system. You have to keep giving yourself a shot every 2 weeks or once a month. So again, a pill works that in a couple days, no shots but weakens your immune system, or a shot every 2 weeks that starts working in a week or two and does not weaken your immune system. Which one sounds better to you?”

Most patients have a very clear either, “I couldn’t imagine giving myself a shot” or “I wouldn’t want to do anything that might weaken my immune system.” If they say pill, then I’m going to talk about the boxed warning. “I do have to tell you it’s going to have some things that sound really scary.” The advice I have for everybody is when you’re talking about the boxed warning, don’t start with heart attack, stroke, death, and cancer. Start with, “Some things sound really scary. The data we have about this medication haven’t shown an increased rate of these things. But the FDA wants you to know about them because a different medication used in people who don’t have eczema that’s distantly related to this medication did slightly increase the chances of these scary things. But again, for this medication, none of the information we have about it has shown an increased rate.”

I do want you guys to know and our viewers, I didn’t say it doesn’t increase the rate. I said the information we have has not shown any increased rate. I said scary things a couple of times. I’ve said distantly related medication, people who don’t have eczema. Then I say, “The scary things, just so you’re not surprised when you get it, are things like heart attacks, strokes, and blood clots, and cancer. But again, all the information we have about this medication has not actually shown an increased rate of those things happening.” That makes people more comfortable with the JAK [inhibitors], and I don’t feel like I’ve said anything inaccurate. If that was taped and played in court, everything I said was right, and I stand behind everything I said. My pearl is shared decision-making and how I talk about the JAK boxed warnings.

 It makes me think about a quote that is often attributed to Confucius. It might be apocryphal because people attribute a lot of quotes to Confucius. But it’s, “Because the newer treatments are good, it does not follow that the old ones were bad. For if our worshipful and honorable ancestors had not recovered from their ailments, you and I would not be here today.” But they are really nice, and to have some new treatments and be able to talk about these with our patients has changed the game. I think this is the beginning of a new era in atopic dermatitis. We can now promise things and deliver in a way that we’ve never been able to before. I’m really excited about this, and also excited to see where it’s going.

 I would add that the patients who present to our office who are most undertreated are still those moderate patients. I would say my pearl would be looking, as we’ve all said today, at the patient holistically, not just the BSA [body surface area] of that patient on one day and time but considering other factors like the impact of itch. Sometimes I look at something called the BSA of itch, where you’re saying, “Your skin disease is 5% today, but where are you itchy? How is this impacting your life?” The moderate patients are as impacted quality of life-wise by their disease as our severe patients, if you look at the studies. So, make sure you are presenting your options.

I like what Aaron said, even when you have a mild patient in the office, I often say, “You look good today, but I want to show you the runway, which is very different than it was 5 or 10 years ago. If your disease control is to change, if your satisfaction about your treatment or something about your life is to change, if your disease is to change in some ways, I want you to know that other treatments exist.” Because for so many years for these patients, they didn’t. Still, I think there’s lack of awareness of our advanced therapies for atopic dermatitis. It’s capturing the moderate patients, it’s getting all of our patients to higher levels of disease control. I agree with Peter, I feel so lucky to take care of these patients in the year 2023, and I think we’ll only feel that amplified in the years to come.

This has been a fantastic discussion. I think we’ve all learned from each other. I want to thank each of you for this informative discussion. And I want to thank you all for watching this 

. If you’ve enjoyed the content, please subscribe to our e-newsletters to receive upcoming peer exchanges and other great content right in your inbox. Thanks so much.

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Experts in dermatology share practice pearls and takeaways for treatment of atopic dermatitis.

Pearls for Atopic Dermatitis Management

Aaron, I’m going to come back to you. We have all these wonderful tools, but we know if the patient doesn’t do what we’re hoping they’re going to do, that turns out to be a problem. What do you find, how do you assess that, how do you keep them on track?

Patient adherence is critical in this disease, and there are good data already out there, most recently one paper looking at insurance claim data as well as diagnosis between 2017 and 2019. We recognized that topicals are still the most commonly used treatment. They didn’t dive in exactly into which topicals, but we know that when you get to greater levels of efficacy and you move into the biologics as well as the JAK inhibitors, you’re going to have improved adherence because you’re also going to have better efficacy. It is difficult with these patients with the overall mindset of “I’m better.” As Peter was saying, when do we stop these treatments and these therapies? It almost doesn’t matter what we have to say, it’s what the patients are going to do.

As we get new treatments that work really quickly, I’ve seen some patients adjusting the way they are utilizing these therapies. It’s our job to educate our colleagues, as well as our patients, that this is a lifelong disease, although hopefully not. There is some question about disease modification that’s getting even more exciting, but we don’t have time to discuss that today. Adherence is of course of the utmost importance and making sure this fits into the patient’s daily life.

Ali, do you have any special tricks or tips you use to make sure the patient stays on task?

 I find my [patient] visits in atopic dermatitis sometimes are opposite to those in psoriasis because a lot of the patients with atopic dermatitis are less familiar with the chronic and systemic nature of their disease. Atopic dermatitis is a chronic, and for most patients, a lifelong systemic, inflammatory disease. The conversation about long-term control, and in some cases the need for systemic control-long term, becomes easier when they understand their disease as inflammation that’s going on underneath the surface even when they feel better. When they can accept it as a systemic condition, just like we understand many ailments in medicine, that conversation about systemics—like if you stop insulin in a diabetic, your diabetes would still be there–it becomes easier to understand.

I always say, “Let’s get you clear and then we’ll reassess.” That needle might move, and that’s due to some of the exciting things coming through the pipeline. But for now, setting them up to say, “This is a great time to have atopic dermatitis. For the first time, I can offer you something safe for you to stay on long term that is going to get you to a better level of control.” It was not something we could say before. It’s made that conversation much easier.

 That’s an important point. Patients present to us in a variety of different ways. I’m finding now some obviously are presenting 

, new with disease, and so we’re able to get these better treatments to them earlier. Sometimes the discussion is easier with a patient who has had atopic dermatitis for 10 years, and for whatever reason they weren’t offered or maybe they didn’t consider some of these other more advanced treatments. It’s sort of a different discussion with each of these patients.

 It’s a disease state re-education. A point that Matt brought up, which I completely agree with, is that flare anticipation. It’s not only the parents feeling desperate that they can’t manage their child’s atopic dermatitis, it’s that adult patient saying, “Why can’t I get this under control? Why can’t I just be clear for a while?” It’s saying, “because it’s out of your control. This is completely not dictated by that allergy you’re trying to find, but because it’s a systemic disease.” Once that acceptance happens, I feel like the conversation becomes easier. That dominates a lot of my initial visit time and is why I run behind all the time.

Expert dermatologists discuss treatment discontinuation as a barrier to achieving desired outcomes in atopic dermatitis.

Patient Adherence in Atopic Dermatitis

Aaron, we have some other players now in the biologic realm. We have tralokinumab, which has been already FDA approved, and we have lebrikizumab, which is soon to be FDA approved. Can you comment a bit on what we expect from these?

 As we all talked about, it’s a great time to have atopic dermatitis because we’re going to have more treatments coming down the pipeline. So lebrikizumab, which we’re not going to talk about in depth today just because it’s still being studied, and there are even a few more beyond that. But we cannot forget about tralokinumab, another very important first-line agent. It is an IL-13 [interleukin-13 inhibitor]. Again, when you look at the studies, it’s very efficacious, very safe. The important key part here is that not every drug is going to work for every patient, and so it is important to have these different options. As Matt has already discussed, dupilumab works great, but there are some adverse events. When those happen, what are we going to do? I need other options, and that’s where tralokinumab comes in. It’s another great option to have for us in treating these patients.

Do you feel or are there data to show that if somebody doesn’t reach where they need to be or has an issue with dupilumab, that we shouldn’t consider something that is potentially an IL-13, or is that a viable option?

 That’s a very important point. Obviously, these are different drugs, and they bind differently as well, even on the same molecules. It is important to recognize that if you do switch, you may get different efficacy. It’s not to say one is superior or inferior, it’s just that people are different, their diseases are different, and we need different treatment options. Another thing that Matt had mentioned is EASI-75 [75% reduction in the Eczema Area and Severity Index], and what about those higher numbers like EASI-90? Getting full clearance, I know we haven’t talked about it, but that really is our goal. That’s really what I want for our patients. I want an IGA [Investigator’s Global Assessment score] of 0.

I want it to be completely clear, not almost completely clear, but completely clear. Because not just in the eczema disease state but other disease states, what have we learned, what have we recognized? Sure, if you get them 75% clear, it’s going to have a huge impact on their life. You can have even more of an impact when you get them to 90%, or the holy grail, get them completely clear. As somebody with very significant allergies myself, you start to just live with these symptoms. You think, well, this is maybe as good as it’s going to get. Matt, I came into your office, I’m OK, I’m doing all right. But wait, I can get even more clear? I didn’t even realize how great that would feel. I can actually breathe now. So really pushing the next line of treatments, including utilizing a variety of the ones that we have now, sometimes even in combination, is very important.

I want to give a realistic illustration of the difference between an EASI-75 and an EASI-90. One of the ways I like to explain it is, when you’re bad, as a moderate to severe patient, you can’t go to Macy’s and try on clothes. Because if you try on that white blouse, you’re going to bleed through and then you’re going to have to buy it because you bled on it. So you think about the fact that I can’t go do an activity that I would love to do. When you get to EASI-75, I can now go and try on clothes. I’m not going to bleed on them. I’m going to be able to go in the dressing room and be OK. But you get to an EASI-90, I can now put on a bathing suit and go out to the pool or the beach and nobody’s going to look at me funny and wonder what’s wrong with me.

 There was a series of about 28 patients from a European center who either had an inadequate response or an adverse effect from dupilumab and got transitioned to tralokinumab. If you did not respond adequately to dupilumab, there was a 50-50 chance you would respond adequately to tralokinumab. Now on the other hand, the red face that we sometimes see with dupilumab, that pretty much went away in everybody when they switched onto tralokinumab. The conjunctivitis, again, was kind of 50-50.

We need those data. We keep encouraging them to please show us, tease out those data of patients who are in one similar category to the next.

Aaron S. Farberg, MD, comments on use of different treatments for atopic dermatitis when a patient does not respond to treatment.

Use of Tralokinumab in Atopic Dermatitis

I would like to move a bit deeper and talk about what treatment options are available. Matt, if you don’t mind starting us off, dupilumab was revolutionary for our moderate to severe patients. It changed so many lives. What did we see in the clinical trials? What do we see in real life in terms of efficacy and safety?

 Dupilumab, as you say, is absolutely revolutionary. When it hit the market, we got to see what it did for patients, and wow. It starts working very quickly. We’ve got data out there that within the first week, sometimes less than a week, we start to see improvements in itch and thereby improvements in quality of life. It starts working very quickly. And then the overall efficacy, one of the interesting things in atopic dermatitis is asking which end point we should care about. Very quickly, we’ve got EASI [Eczema Area and Severity Index] scores of 50 to 100, IGA [Investigator’s Global Assessment] scores of 0 or 1, Itch NRS [Numeric Rating Scale] score of 4, then we’ve got quality of life measures. We’ve got Itch NRS 0 or 1, which is an itch-free state.

What’s the right end point? If you just ask patients, would you rather get 50% better or 75% better, they will say 75%; 75% or 90%, they say 90%; 90% or 100%, they say 100%. “OK, I’ve got one that’ll get you 100% better, grow your hair, get rid of your wrinkles and whiten your teeth. I’m going to call that one, it’ll get you to 120%.” That’s the one I want, right?

There are data that give us a hint that EASI-75 [75% improvement from baseline] is where we see topical steroid use drop off. While certainly we want the best outcome we can for a patient, I most closely pay attention to EASI-75. I want to have a level playing field where this is what I’m going to look at from drug to drug. I think EASI-90 or IGA 0 or 1 probably differentiate the drugs a bit better. But something that happens in atopic dermatitis much more so than in psoriasis is the challenge of comparing trial to trial. I know we’re not supposed to do that, but psoriasis results are pretty darn consistent from trial to trial.

In a number of atopic dermatitis trials, even the 2 identical phase 3s that the FDA requires, you’ll see a 10% difference in efficacy…that’s a real difference. So, we really have to be careful in atopic dermatitis comparing trial to trial. If one drug got 90% of people to EASI-75, and another one got 40% of people to EASI-75, I would say the 90% one is better. But EASI-75 versus EASI-70, or EASI-73 versus EASI-67, I don’t think are real numbers. I don’t think we can hang our hat on those differences. Dupilumab, whenever we look at the EASI-75, which is my favorite end point, combined with topical steroids gets about 65% to 70% of people to EASI-75. If we look at a higher end point, IGA 0 or EASI-90, it gets around 50% of people to that end point.

As those of us who do trials know, there are specific definitions of what clear or almost clear means. The way that you should think about it as a clinician, a patient who’s clear is clear. But I’m always like, “What the heck does almost clear mean?” The way that I describe almost clear in a clinical sense is the patient says their eczema is gone. If you say to the patient, “Do you have any eczema?” If they’re an almost clear patient, they’re going to say, “No, my eczema is totally gone.” Whereas you’re going to notice, “Oh, behind your left knee there’s a slight bit of pinkness you didn’t even notice.” That’s almost clear. But for our friends out there who are clinicians and not trialists, when you see the 0 or 1 data, that’s how many patients are going to come back and say their eczema is gone. A score of 1 is not really quite gone. I describe a 2, which is as mild, as a patient who’s going to come in and say, “Compared to where I started, it’s not that bad.” That’s really the clear or almost clear. With dupilumab, we get about 50% of people, whenever you combine it with topical steroids, where the patient would say their eczema is gone.

Safety with dupilumab is really interesting. I honestly say to patients, it is safer to be on this drug than not on this drug. That really comes from the infection data. We know that the risk of skin infections, and I use the term MRSA [methicillin-resistant 

] rather than saying staph. Because if you say staph, a patient’s like, “What?” If you say, “Well, you’re less likely to get a MRSA infection,” now the patient’s like, “Oh my God, it’s going to protect me from MRSA? Yes, I need to be on that.” The data for dupilumab has shown a 40% reduction in the risk of skin infections.

With adverse events, we know conjunctivitis is relatively common. The real challenge with the conjunctivitis is there’s no gold standard for differentiating conjunctivitis because you have allergies or you have dry eye, from a drug-induced conjunctivitis. The best numbers we have say that probably 7% of patients on dupilumab will get a dupilumab-induced conjunctivitis. Again, the problem is we know that about 20% of people will get a conjunctivitis, and there’s no gold standard for knowing which 13% were just because you got conjunctivitis and which 7% were from dupilumab. I never use the term conjunctivitis when I’m talking to a patient. I say bloodshot eyes because the patient doesn’t know what conjunctivitis is. If I say bloodshot eyes, they know what that means. So I tell them, “If you get bloodshot eyes, give me a call.” If they get bloodshot eyes, I send them to see an eye doctor. Like we said, we know that about 7% of patients will get dupilumab-induced conjunctivitis. As long as it’s managed appropriately by an ophthalmologist, we can almost always treat through it if we want to.

The other interesting adverse event with dupilumab that’s now in their label is arthralgia. We don’t have great numbers around this, but it’s about 1 in 250 patients seems to be the best number for how many will get what we would call a meaningful arthralgia. Now it’s more common than that if we say a bit of arthralgia. If it’s just a bit of arthralgia, which is relatively common, but those people don’t even notice it. If you ask, they’ll say, “After my shot, my finger hurts for 2 days.” That’s maybe 1 in 20 people, but it’s an irrelevant thing; 1 in 250 people get real arthralgia.

In terms of dupilumab’s impact on quality of life…there are major improvements in anxiety and depression, and quick improvements in anxiety and depression, major improvements in sleep quality. It’s always interesting trying to tease these things out. Is the anxiety and depression getting better because the itch is better or because they’re sleeping better? We don’t really know. It’s almost impossible to tease them out.

Other places where it starts to get interesting, there’s an increase in the diagnosis rate of ADHD [attention-deficit/hyperactivity disorder] in children with atopic dermatitis. We don’t know if that’s a true pathophysiologic association, or if the sleep deprivation makes them more irritable, or if the itching makes them seem more distracted. But the latest study that came out showed there was a decrease in the use of stimulants in children who were on dupilumab. Because people thought they must not really have ADHD, they got diagnosed with it because they were scratching and distracted all the time. Well, if it’s getting them off of their stimulants, I don’t care.

 I’ve heard that over and over, a patient saying this gave me my life back, and that’s a powerful moment when you say, wow, you’ve come alive now because this disease had held you back so much. I think those are the kind of end points we’re looking for where people feel like they have control.

And for the first time, we’re able to deliver that. In the past, we haven’t been able to do that. Matt, that was a lovely overview of the revolution that we’ve seen when dupilumab came into the picture, an IL-4 [interleukin-4], IL-13 inhibitor.

Expert dermatologists review the positive impact dupilumab has on quality of life for a patient with atopic dermatitis.

Matthew Zirwas, MD

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