Northwestern University Feinberg School of Medicine

Peter A. Lio, MD, Northwestern University Feinberg School of Medicine 

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 

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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’ll toss it over to Peter and think about our more classic oral agents, methotrexate, cyclosporine. Maybe you can, for those who aren’t super familiar, tell us how long these have been around as an important mainstay for therapy. What are some of the challenges patients have in terms of adherence, and ease of use, and burden with these therapies?

I feel like once we have maximized and optimized our topical therapy, and my area of focus is trying all these crazy alternative and integrative approaches as well, but once we feel that we have done as best we can with that and we’ve maximized that, then I think we have to start bringing up the potential for going to a systemic agent. We know historically we’ve had, all off-label by the way, none of these we’re about to talk about are FDA approved. Well, let me say 1 is FDA approved that’s been grandfathered in, and that’s prednisone. Systemic corticosteroids technically are approved for the treatment of corticosteroid response to dermatoses, of which this would fall in place. But of course, we often try to push against using those because not only do they have a whole host of potential adverse effects, but for some patients, they can cause a pretty terrible rebound flare-up. I inherited, and I’m sure all 3 of us have inherited, lots of tough patients who have kind of become corticosteroid addicted or are really used to it, and that is a bad plan for most patients.

Now, do we meet people who sometimes use them and say I’ve never had trouble? Yes, but we’ve also met people potentially who say they’ve played Russian roulette for years and never died, but I wouldn’t recommend it. I don’t think it’s a wise game to play. I try to avoid it. Are there times when we need to use systemic corticosteroids? Yes, I would argue there are certain scenarios to use them as a rescue. If somebody’s going to Europe, somebody’s getting married, you just kind of have to do it. But in general we try to avoid it. So let’s take that off the table for a minute.

Then we have our conventional immunosuppressants. Methotrexate, cyclosporine, mycophenolate, azathioprine, those are the big 4. Most dermatologists in the United States, in particular pediatric dermatologists who use them more than adult dermatologists in this context, they’ve picked cyclosporine. I think cyclosporine really is the drug of choice. If you look, there’s this wonderful figure I was able to put together. Somebody helped me do it, but we put it together looking at the discontinuation rate of the conventional immunosuppressant agents, and it turns out that the best bang for your buck is cyclosporine. It still isn’t pretty. Many people have to discontinue due to potential adverse effects, and relatively few people get good control on that medicine long term, but compared to methotrexate it’s unbelievable.

Methotrexate is quite terrible. Approximately 6% of people get control on methotrexate, and mycophenolate was approximately 11%. These are very low numbers. I feel like it’s the wrong tool for the job for most patients. It’s kind of like using a brick to hammer in a nail, it can work, but there are all sorts of issues. Of course, with all of these agents, we have a whole host of potential adverse effects, lots of monitoring we have to do, and they’re all off-label. It’s very challenging to use them, and we’ve done it, but I think cyclosporine has been my favorite. Britt, for you too, I know you have mostly pediatric patients, do you use cyclosporine as your first line before some of the newer agents came out?

Before they came out, yes for sure. Now, I joke that the residents aren’t going to know how to use this for atopic dermatitis anymore. I think especially if you want to try to cool someone down quickly, that was always our go-to for a severe patient who failed topicals, and/or phototherapy, or where phototherapy wasn’t a reasonable option. I used a lot of it. But again, you can’t use it forever, there’s a big conversation about risk, you’re subjecting a child to blood draws. It is something that you have to worry about the patient adhering to it. You can’t give someone a prescription for 3 months and just let them go. It’s very labor-intensive on the part of both the family and the clinician because of the monitoring.

This thought about the labor associated with thinking about the treatment, then talking about the treatment, then monitoring for the treatment, and then thinking about when to stop it, that’s the big thing. It is a labor that’s on us, and it’s a labor on the patient and caregiver. If anything could highlight why we needed a bit of a revolution in treatment, I think that was it. And the fact that, bottom line, it works for some people but not everybody. You’re not getting people to the point of saying, “OK I’m almost completely clear and can get my life back.”

Peter A. Lio, MD, describes the challenges pediatric patients face with oral therapies for atopic dermatitis, focusing on ease of administration and patient adherence.

Peter A. Lio, MD, Northwestern University Feinberg School of Medicine

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