Are You On Top of Pediatric Atopic Dermatitis? Expert Guidance for Leveraging the Latest Advances in Systemic Therapy

Wendy Smith Begolka: Our first panel discussion is going to be how do patient and caregiver-reported outcomes inform your assessment of pediatric patients with atopic dermatitis. In terms of what standardized questions or tools you might use, and other questions you might ask. I will start with Dr Swanson as our pediatric dermatologist. How would you answer this?

Dr Swanson: I think most of the time in clinic, I just have a discussion with the patient and their family about how the eczema is affecting them as a family unit. How is sleep? How is school? How is work? How are friendships? Are we going to sleepovers? Are we playing the sports that we like? What is the true impact of the atopic dermatitis, and is the current regimen that we are on helping to control and normalize that, or are we still struggling? I think if I use a standardized tool, I probably use the ADCT, the Atopic Dermatitis Control Tool, which is just 6 questions that the patient and their family answer about the state of control of their eczema. Most of the time, I am a conversation girl.

Wendy Smith Begolka: Dr Lio, how would you answer that?

Dr Lio: I really like the conversation part too. In the last few years, I have become a bit of an evangelist for this special tool called the Atopic Dermatitis Control Tool, or ADCT. I really love it because it gives a little bit of structure and gives us a number at the end that I find a lot of my patients really, maybe they did not even expect to like it, but now they talk about it when they come in, and they tell me the update because they can do it themselves too. It really gives just a little structure to that conversation. I never thought I would say that about a tool like this, but this 1 has stolen my heart.

Wendy Smith Begolka: Because you both mentioned the atopic dermatitis control tool, how do you think that that has allowed you maybe, to get a sense of disease progress or maybe regression over time?

Dr Swanson: Go ahead, Dr Lio.

Dr Lio: I will just finish my thought with this idea that - really what has been interesting for me is that sometimes a patient will come in and say I will say, how are you doing? How are things? They will be like, oh, I am pretty good. Everything is pretty good. It looks pretty good that day. Maybe they are feeling good. Then I ask these questions, and by question number 3, they are like, oh, maybe I am not that good. I have had some patients start to cry and say I thought I was feeling pretty good today and maybe I am, but you are right. In the last few weeks and especially this last week, because that is really how the ADCT is structured, it is like I actually have had some hard times still. Maybe I am not out of the forest yet. You know, we are still in some trouble. I think it can be enlightening from that perspective.

Dr Swanson: I think to that point, a lot of patients come in, and maybe they have been started on a novel topical or their first systemic agent, and they are improved from where they were at. To them that feels like, wow. They might not fully realize the impacts that are hiding that they are not even thinking about because they have been slowly acclimating to the burden of atopic dermatitis during their disease course. Sometimes I think that there is that analogy that you can burn to death in a slowly heating bathtub. I think eczema can be that slowly heating bathtub for a lot of families because they just do not fully realize the impact. So you make that a little bit better, and they are pleased, but then you point out the other impacts that are still a problem with something like the ADCT.

Wendy Smith Begolka: That is so interesting, pointing out the things that even maybe the patients or caregivers are not appreciating. Dr Swanson, maybe can you elaborate a little more? Is there a particular aspect that you think is most often overlooked?

Dr Swanson: I tend to focus a lot on sleep, both for the patient and their family members, because if 1 little kid has eczema in the family, the entire family unit suffers, and sleep is so important for so many things. I dive into that. I think most families are aware of the impact on their sleep. I think 1 thing that is probably overlooked by families until we start talking about is the impact of eczema on growth. We know that kids with bad eczema tend to be small on growth curves for height, and there are a lot of theories as to why.

I subscribe to the theory that it is due to poor sleep. When you have eczema, you do not sleep as well, and you do not enter REM as long or as often. It is during REM sleep that growth hormone is secreted, so physiologically, these kids have lower growth hormone. If you make that better, then you allow them to grow. I found that talking about growth is a needle mover, pun intended, when talking about potential systemic therapy for atopic dermatitis.

Wendy Smith Begolka: That’s super interesting. Dr Lio, anything to add on that?

Dr Lio: No, I think that says it all. I love it.

Wendy Smith Begolka: Thank you both for that first brief panel discussion.

[00:20:49]

Leveraging Patient-and Caregiver-Reported Outcomes to Address the Burden of Pediatric Atopic Dermatitis

I think that that is a great lead into the next section of our presentation today, which is on leveraging patient and caregiver-reported outcomes to address the burden of pediatric atopic dermatitis.

[00:21:01]

Poll 3

We are going to go ahead and start with a poll again. Which of the following statements is a myth regarding the real-world burden of pediatric atopic dermatitis? Is it

1. Children with moderate to severe AD often experience sleep disturbances due to nocturnal itching; is it
2. Caregivers of children with atopic dermatitis frequently report minimal interference with daily routines and emotional well-being; or is it
3. The impact of pediatric AD extends beyond physical symptoms to include social and psychological challenges for both the patient and family.

Go ahead and cast your votes this is which 1 is the myth? We have got about 66% correctly identifying the myth here, which is that the caregivers of children frequently report minimal interference that is definitely the case here. Let us talk a little bit more about that here on the next few slides.

[00:22:06]

Atopic Dermatitis and the Impact of Itching

The burden of atopic dermatitis is definitely multidimensional, and you have heard our panel members already speak to that a little bit today. It is something that can affect really every aspect of an individual's life, with much of it being unseen and only really able to be ascertained from the patient or caregiver’s self-report. By far and away, the most burdensome symptom of atopic dermatitis is reported in numerous studies. If you have got a group of patients together, I am confident you would hear the same thing. It is going to be the itch.

It gets this rank because the impacts of itch are really 24/7 and really lead to a number of other downstream impacts that are shown by example in this slide. It certainly starts with the itch leading to scratching and leading to open sores or wounds, and to the sleep loss. We have touched on that a little bit, but it then can continue down this cascade and have a lot of different interrelated impacts on their life, as well as culminating in impacts to their mental health as well. In the next few slides, we are going to highlight some of these aspects in a little bit greater detail.

[00:23:13]

Patient Burden: Itch

Starting first with looking more quantitatively at itch per se, as you might suspect, with increasing disease severity, as shown by the stoplight colors here of green, yellow, and red, as with increasing disease severity, you can see that itch goes up and to the right. This is actually looking at the pruritus numeric rating system or numeric rating scale on a 0 to 10 scale. You can see that, for the most severe of individuals, you typically are getting scores anywhere above 6 or 7, upwards of even closer to 10, and that really is holding, regardless of what age of patient that you are looking at or caregiver report.

Even for those with mild disease, I want to point out as well, the amount of itch that is shown here is certainly less by comparative to moderate or severe disease, but by no means is considered minimal in the broadest of senses, when looking at it from a patient burden perspective.

[00:24:13]

Patient Burden: Pain

When we also look at beyond itch, 1 of the things that was highlighted on the slide is that you can also get skin pain from itch, but you can also have skin pain in and of itself as a symptom. This is something that is become to be appreciated as a slightly newer aspect of understanding the patient burden of disease. Once again, regardless of whether we are looking at mild or moderate, or severe disease, you have the same up and to the right with increasing severity. You have increased patient report of this symptom, and you have increased severity of this particular symptom. Again, this 1 is using a pain NRS scale instead of the pruritus NRS scale, but the same intention still holds.

[00:24:52]

Patient Burden: Sleep

When we look at sleep, this 1 is looking at it slightly differently. As you might again suspect, that higher and or increased atopic dermatitis severity is associated with more frequent sleep disturbance. This is both not only the level of sleep impairment from a standpoint of getting to sleep, but also staying asleep, and it can be quite profound if we focus really on, I would say, the orange and the purple aspects of this graph. You can see that definitely, upwards of 70% of individuals that have severe disease are saying either every day their sleep is affected, or at least 5 days out of the week their sleep is affected.

This goes commensurately down with disease severity again. But again, I think you can see with even with individuals that have mild disease, they are having some sleep effects and sleep impacts on their life. As Dr Swanson indicated, this lack of sleep is actually compounded for individuals in the pediatric population, for the caregivers, because when the kids do not sleep, the parents are not sleeping. What I really appreciate about this slide is that the quotes on the right-hand side convey in a more qualitative way from the perspective of a patient or caregiver, the stark reality of what it means for affected individuals and what it means to not have sleep, which can have a lot of downstream effects on their personal life as well as their social life.

[00:26:10]

Patient Burden: Quality of Life Impact

Which then takes us to more of a sense of quality of life impact. This is a very broad category. Again, essentially what you are seeing, using the same stoplight approach, is that up and to the right. This is actually looking at the CDLQI, which is the Childhood Dermatology Life Quality Index, where anything that has a score above 13 means that they are having a very or extremely significant and negative effect on their quality of life.

Again, not surprising that those that are in the moderate and severe camp are definitely well above that scale. But those that are even in the mild section of it in the green, can have individuals that are approaching a more significant impact to their quality of life. This severity is also associated with other tangible impacts, such as increased school absences, especially for the pediatric population.

[00:27:05]

Patient Burden: Stigma and Bullying

Then, as we look beyond the physical aspects of things, we are moving into the space of mental health in this slide. What this slide is showing is that there can be significant stigma that is attached to having a visible skin disease like atopic dermatitis. If we look at the data on the right, but I will just read the bullets that are on the left, that adolescents with atopic dermatitis actually experience an increased frequency of bullying compared to those without atopic dermatitis, and that children with this skin disease are actually reporting discrimination related to their visible symptoms.

They can have fewer friendships or challenges with forming friends and having different abilities to engage more socially, because they also can choose to have decreased school and extracurricular involvement. That external stigma actually compounds some of the internal stigma that these patients are also experiencing, really resulting in atopic dermatitis often being a very isolating disease for individuals.

[00:28:04]

Patient and Caregiver Burden: Topical Corticosteroids

Then, while we have also talked about now the burden of physical disease, we talked a little bit about the burden on mental health. This is looking at the burden of treatment at least a little bit, both from a time perspective, but also the concerns about using certain therapies. This is talking here specifically about the burden of using topical corticosteroids. We know that this is a very commonly used therapy. It certainly has its place in atopic dermatitis care. Later, we will hear about other options. There certainly is a lot of anxiety amongst the caregivers and amongst children that are using different topical corticosteroids, whether it is about using them for the long-term or concern about side effects, or how well they are going to work.

[00:28:47]

Impact of AD on Caregivers

Then, as we have already touched on while we are talking about the patients and the caregivers collectively, this slide is really focused on the impact of atopic dermatitis on caregivers, and they can have a very similar profile of burden of disease. As we have been talking about, atopic dermatitis, when it affects a pediatric patient, can be something that really is affecting the whole family unit, so you have disruption of family time here. We have already talked about loss of sleep, but can have other tentacles, into the family life with leading to different aspects of financial worry, care, coordination, work productivity and then other relationships between other members of the family as well. When so much attention and focus is given to the child who is affected.

[00:29:32]

Clinical Assessment Tools

Coming back then to where we started, there are a number of different ways that these different elements of burden can be captured in clinical practice. Several of those tools are shown on this slide specifically, and were highlighted in some of the previous slides. The idea here is to pick 1 that fits your practice best and can help you really identify opportunities to work with your patients to understand how these tools can be useful adjuncts to asking other questions as Dr Swanson indicated, to align on the progress that they might be making with treatments, or uncover different unseen aspects of the disease burden and ultimately align on therapies that are going to work best.

[00:30:12]

Posttest 1

With that, we are now moving to our post-test question. Our first 1 here, which is that now we have a 7-year-old child with atopic dermatitis who presents with worsening pruritus and sleep disruption, despite ongoing topical therapy. The caregiver reports increased emotional distress and absenteeism from school. Which of the following tools would best support shared decision making about advancing therapy? Is it the

1. IGA, the Investigator Global Assessment; is it
2. The Eczema Area and Severity Index, the EASI score; is it
3. The Patient-Oriented Eczema Measure or POEM; or is it
4. The Scoring Atopic Dermatitis or SCORAD.

Please enter your answer. How do we do? Still a little all over the place with this, but the majority of individuals got the correct answer, which is our POEM score, because this is a validated patient-reported outcome tool that is going to capture our symptom severity from the patient or caregiver's perspective over the prior week. It is going to focus on those quality of life issues that we have talked about itch, sleep and a few other things. It really is very helpful. In contrast, some of the other tools are really more clinician-assessed and may not fully capture that burden, but they can still be very helpful with for sure. With that, I think we are going to move to our next panel discussion.

[00:31:53]

Panel Discussion

I invite Dr Lio and Swanson to come back. We are going to start to talk about a few different questions that are on the slide here around different therapies that we might be using for children with atopic dermatitis based on some of the burdens that we have spoken. Let us talk first about some of the limitations of topical therapies for children with atopic dermatitis. This time, let us start with Dr Lio.

Dr Lio: We know that topical therapies are really the keystone of all the treatment. We are going to start everybody on them first. When we move to systemic sometimes you will hear people say, oh, once you are on the systemic therapy, now you can stop your topical. No way. Your topicals are still important. Now, ideally, you are going to be using them much less and maybe less potent ones and stuff when you are on the systemics, but they are still really important. That said, there is a lot of limitations.

Sometimes, it is just too severe, like I will try even pretty strong topicals, and it is not budging. It just laughs at it, or it does not do enough. The second situation is when it is too much body surface area. It is really hard to consistently put medicine on, I would even say, more than 20% of your skin. 30% for sure. You are putting stuff all over the place, and it really gets tiring for patients and families. Then the third piece is the limitation for especially our topical steroids and frankly, our topical JAK inhibitor as well, the ruxolitinib is they really have a time limit on them. You cannot consistently, continuously use those. You should take breaks. Some of the other ones are ok, all of these are limitations that make it tricky.

Wendy Smith Begolka: Dr, Swanson, given all of those limitations, when would you be considering a systemic therapy for a child with atopic derm?

Dr Swanson: I would even throw 2 other limitations that lend itself to thinking about systemic therapy. Number 1, burning and stinging. A lot of patients with atopic dermatitis have tactile sensitivities, and a lot of things will burn and sting, which makes topical therapies just really hard to manage. The second thing is families that feel like they are playing a game of whack-a-mole, so they get the eczema cleared up over here, and then, lo and behold, it pops up over here, and they just never feel like they are getting ahead of it. I think any time optimized topical therapy is not achieving milestones, I am going to talk about systemic therapy. That boils into a lot of things, like how it looks in the office. The patient reported symptoms of itch and sleep, and school, and sports, and all that stuff, and then what therapies that they have tried and failed.

Wendy Smith Begolka: You mentioned something really interesting there, just about optimize topical therapy. How are you assessing that for your patients?

Dr Swanson: I think it is a lot of patient-to-patient dependent. I am making sure that I talk about the importance of sensitive skin care that I do not forget to talk about that. Then I talk about the topical therapy options available to them, given age and severity of their atopic dermatitis, and we have selected a good combination or a good 1 or 2 topical therapies. Then I see them back, and they are just still not getting there.

I actually had a patient just today that I was talking to Dr Lio about before we started, where he had had atopic dermatitis for years and years. He is 13 now. It started when he was about 1 year of age. He had been through all the topical steroids and wet wraps and topical calcineurin inhibitors and all, even prednisone intermittently, not by me, but from other people. Then I met him for the first time 8 weeks ago, and I talked to them about some of the new level topicals, because he only has about, I do not know, maybe 10%, 12% BSA. So we chose topical ruxolitinib. I saw him back today and it had not budged at all, which is surprising because topical ruxolitinib is quite effective. You put your brain through the paces of, am I sure this is atopic dermatitis, given that failure? Yes. It still looked like atopic dermatitis. We talked through all the systemic therapy options, and we picked 1, and we started it today, and hopefully it will yield the positive results we are looking for.

Wendy Smith Begolka: I appreciate you sharing that recent experience as well so with that, maybe we will go ahead and transition over to Dr Lio to tell us a little bit more about systemic therapy in children with moderate to severe atopic dermatitis.

[00:36:09]

Systemic Therapy in Children With Moderate to Severe Atopic Dermatitis

Dr Lio: Yes, this is when things heat up to a certain level. We need to go to that next step.

[00:36:15]

Poll 4

Let us do some polling questions first. Which of the following is a myth about targeted systemic therapies in pediatric atopic dermatitis? Would you say

1. Targeted systemic therapies are generally considered for children with moderate to severe disease who have failed optimized topical treatments;
2. All children with AD are eligible for targeted systemic therapies, regardless of disease severity or prior treatment history; or
3. Clinical trials have demonstrated that targeted systemic therapies are safe and effective in pediatric populations.

A lot of people picked the second choice, B, as the myth. I think that is pretty good because we know they are not really designed for all severity levels or prior treatment history. We really want to make sure they use some of those things. I think that is the correct answer.

[00:37:15]

Candidates for Systemic Therapy

We know that when we look at the whole population, it could be as high as a third of the pediatric patients with moderate to severe atopic dermatitis. Those patients seem to be inadequately controlled with topical therapies. Honestly, 1 of the interesting things is it is a bit of a moving target. I think our threshold continues to get lower and lower to switch somebody up to systemics. 15 years ago, we had nothing. I think we were like, well, you are doing ok. I do not think we want to put you on an off-label immunosuppressant. It was a much bigger deal, much bigger risk-benefit trade-off.

But now, when we have safer, more targeted treatments, it is like, well, we can do better than this, and I think we can actually change the calculation for these patients. We know there is a pretty sizable group of kids out there that are not doing as well as they could be. Why does that matter? It matters because they are suffering. They are really miserable, and it affects everybody, as you have heard. It is not for fun. It is not a cosmetic thing. We are not trying to put it in the water or sell something. We are really trying to get these patients to a point where they are comfortable.

I think that discussion has to happen between patients and families, and caregivers. It is a real shared decision-making thing. I never push. I meet a lot of families who feel hesitant about especially stronger treatments, and they are like, we are afraid we do not want to do this. Do you feel like we need it? Also, our main piece is when we have done a good job with our topicals, but we really feel like we are still struggling. We are having especially sleep issues, especially potential for recurrent infections, these are big deals. I take all this into account. We look at the severity of disease, and we have a heart-to-heart I never push.

[00:38:47]

Traditional Systemic Therapy

If they do not want to do it that day, then I will say, you know what? Why do not we see how things go? We can make some tweaks. We can re-optimize topicals and I am like, you, come tell me when you are ready, and a lot of the families, sometimes they will call me that night and say, we have been thinking about it and we really do think we are ready, especially around bedtime when the kid is scratching and uncomfortable and they are like, all right, we have we have done our best.

Again, I am old enough to tell you that there was a period when we really did not have great answers at that point where we just said, well, good luck, and now I am so happy that we do. When we think about this in general, we are really trying to use as little systemic therapy as we can. We are not trying to overdo it. We are always using our adjunctive therapies. I often talk about a finite timeline. Some of the companies get mad at me when I say this. The pharmaceutical companies will say, we really like to think of it as a chronic treatment. I am like, I get it. I understand your perspective. Let me tell you my perspective and the patient's perspective that this is a disease of vicious cycle. So, my dream here is to break the bad cycle, the vicious cycle that we are stuck in, itch scratch, skin barrier damage, dysbiosis, sleep problems, break that cycle. Go to a virtuous cycle. Healed skin barrier. Better behavioral patterns. Better sleep. Better microbiome.

Then at some point, maybe 6 months, maybe a year, maybe a few years, it just depends, there is a potential for getting rid of these systemic agents or spacing them out. In fact, some of them, as you will hear about in just a couple of minutes, they actually have a built-in plan to increase the dosing interval less medicine over time. That is what I am talking about. That is really what we are thinking about. One thing I think everybody agrees with is that we want to avoid systemic corticosteroids.

I meet lots of clinicians who say, oh, we do it all the time, Prednisone, prednisolone. We really do not want to do those unless we are up against a wall. They have the potential to make things worse, and that is why it is a little bit of Russian roulette. Of course, we had a lot of agents that we used historically pre biologic era like cyclosporin, azathioprine, methotrexate, mycophenolate. These are fine medicines, and they can help. I have used many of them over the years, but they are really a bad risk-benefit calculation. In general, there are things we do not want to do. Look at azathioprine and methotrexate. 8 to 12 weeks to kick in. We know all of these have multiple boxed warnings. They are troublesome for a lot of patients.

[00:40:58]

Biologic and Small Molecule Targets

I really try not to use them. Do I still use them? Sometimes I do. I run out of options even today. Now we have an abundance of great things from dupilumab, which came out in March of 2017 in the US. Tralokinumab, its cousin, that binds to IL-13, and its more recent cousin, lebrikizumab. They both work similarly on blocking IL-13 dupilumab blocks, IL-4, and IL-13 receptor, that has shared subunit called IL-4 receptor alpha.

Then most recently, nemolizumab, which is neat because that binds to the IL-31 receptor, the master itch blocker, so that is nice. Then, of course, we have our oral JAK inhibitors. In the US, we have 2 of them abrocitinib and upadacitinib. Baricitinib we have for alopecia areata, that is available in some other markets for atopic dermatitis.

[00:41:45]

Newer FDA-Approved Systemic Agents

This is a lay of the land. This is the landscape of our treatments, and this is incredible. Everything really started in 2017, so less than a decade, essentially 8 years, where we have really had all of this stuff, and it is coming fast and furious. The guidelines are getting outdated basically as soon as they come out. Now, are any of these perfect drugs? No. Is there such a thing? They all have real potential issues. They all have real potential drawbacks. But they also can be incredibly helpful. I think all of us can attest these have literally changed the lives of so many patients and have altered the field of atopic dermatitis, how we approach it.

[00:42:23]

LIBERTY AD PED OLE: Dupilumab

Again, I say it as somebody who really gets to straddle the line between pre-biologics and post-biologics. It is a brave new world. It is incredible. Dupilumab came out in 2017 in the US. Really impressive improvement in these patients then it got approved on younger and younger. Now it has a very cool distinction. It is approved down to 6-month-old babies, which is incredible.

[00:42:44]

ECZTRA6 Efficacy and Safety Data: Tralokinumab

It has 1 of the lowest indications. The other biologics are actually all approved down to age 12 years. Dupilumab goes all the way down to 6 months, which is really great for the kids. Tralokinumab quite similar, even though it binds slightly different. Dupilumab binds to IL-4 receptor, which affects both IL-4 and IL-13. Tralo binds to IL-13 directly, and it definitely works. There are these network meta-analyses that try to compare them. We do not have any direct head-to-heads, but it seems like tralokinumab might be a little bit less effective, but honestly, pretty comparable. I have had some patients do really well on it as well.

[00:43:17]

ADore Efficacy and Safety Data: Lebrikizumab

Then Lebrikizumab, the newest of this trio, also binds to IL-13. It binds at a different point, and it binds with a really high affinity. This 1 does seem to be comparable to dupilumab when they do these analyses. A lot of my patients who failed dupilumab for 1 reason or another, have actually done really well with lebrikizumab, so it is pretty neat. They are slightly different, although admittedly, they are different types of Cola.

[00:43:41]

Nemolizumab Efficacy and Safety Data

Where the fourth member of the family, nemolizumab is like an “un-cola”. It is maybe a different type of drink altogether. This 1 is IL-31 receptor blocker, and that is pretty neat, so targeting mostly itch we would say itch first. But, it turns out it actually does help against the skin as well. It just works in a slightly different way. Very safe. It starts out with a monthly dosing where the other ones depending on the age, but generally they all start at every 2 week dosing for the older kids and the adults. This starts out at monthly. When people are better with lebrikizumab and tralokinumab, they can space out from every 2 weeks, every 4 weeks. With nemolizumab, they start at every 4 weeks. They go to every 8 weeks when they are doing better, which is really neat.

[00:44:24]

Biologic Therapy Use in AD

It is potentially just 6 shots per year, which makes it nice. Now we know the good thing is these are done at home, so patients can do it themselves, which is great. They are literally studied when topicals have failed, so we know that they are quite effective even for those tough patients. We know that the effect is durable. Some of the dupilumab has data out for 5 years and 5 years plus. It has been out for so long, and even the other ones have multiple years of durability data, and none of them require any lab monitoring, which is great.

Now, again, there are some things that are important to keep in mind. Conjunctivitis can happen for some people with IL-13. Dupilumab, tralokinumab, lebri they can all affect the eyes, and it is usually not dangerous, but it can be an issue, and we want to get ophthalmology involved. They can all cause injection site reactions. Some of them have things like headache and upper respiratory tract infections, and we should not do any live vaccinations while they are on them.

[00:45:19]

JAK Inhibitors

Now, we also know that the JAK inhibitors are really powerful, the oral JAK inhibitors once daily. Again, we have 2 of them in the US, and that is abrocitinib and upadacitinib. Super-fast, super powerful, but they have boxed warnings that talk about things like risk of cancer, risk of blood clots, risk of major adverse cardiovascular event, mortality, all this stuff, which is a little bit off-putting for patients, and they do require lab monitoring. That is the comparison where the biologics do not have lab monitoring. The JAK inhibitors do.

[00:45:51]

JAK Inhibitor Efficacy and Safety Data

Even though we know they are quite safe in our atopic dermatitis patients, for some patients and families, this can be an issue. Although again, I have many patients doing great on these medicines. They tend to be the third line for our patients, but they are fantastic when we need them.

[00:46:06]

Posttest 2

We will wrap this section up with a post-test. Which of the following clinical profiles most strongly indicates the need to initiate targeted systemic therapy in a pediatric patient with atopic dermatitis?

1. A 5-month-old with AD currently uncontrolled with moderate potency topical steroids;
2. A 14-year-old with AD refractory to optimized topical therapy and history of conjunctivitis;
3. A 6-year-old with moderate AD responsive to emollient therapy; or
4. A 16-year-old with moderate AD with a history of moderate flares during winter and wishes to get early control.

Which most strongly indicates the need to initiate targeted systemic therapy?

I think we can push forward. A little bit mixed results here. This is a hard question. I think maybe the best answer here would be B, a 14-year-old with AD refractory to optimize topical therapy and history of conjunctivitis. I think the distracter here was the conjunctivitis, and it turns out that it is actually not a contraindication to give it to somebody with a history of conjunctivitis. It is possible that they may have a slightly higher risk, but you do not have to worry about it. Somebody with AD refractory to doing good topicals, they probably are still a good candidate, even though they have had some conjunctivitis. I still think it is reasonable for that patient. I think that is the purpose of that question.

[00:47:29]

Panel Discussion

Now Wendy is going to take us back through a panel discussion.

Wendy Smith Begolka: Thank you, Dr Lio, for that whirlwind tour of the different systemic options. I am going to go ahead and start with you. How are you then bringing up all of these options with your patients and caregivers to think about which 1 they might want to pick?

Dr Lio: It is getting harder and harder. There is so many to talk about now. The good thing is that I have a little printout. We go over them, and a lot of my patients have already failed 1 of them by the time they get to me, so I tend to be a referral center for folks that have already failed. My discussion might be a little bit different, but a lot of times it is the same basic thing. Here are the pluses and minuses.

Here is what I think will be very good fit for you. We were talking before this started, Dr Swanson and I were saying the different considerations of when you are going to try different things. I think part of the question is, is there something that is very appealing to the individual patient? For example, every 4 weeks to start going out to every 8 weeks, the injection pain or injection site reaction, the risk of conjunctivitis, maybe that patient has read about this and says I do not want anything that can cause conjunctivitis because my cousin had it.

Can we try 1 that does not? Now we have enough options to go over, but I confess there is a lot of art and not as much science here, because they are all pretty good for the right patient, it can be hit or miss. I cannot predict, and no doubt about it, sometimes we just say, ok, if this 1 did not work, let us just try the next 1.

Wendy Smith Begolka: Maybe I will go ahead and ask you, Dr Swanson, to comment on that. Then also I will have you start to answer 1 of the questions that was submitted, which was that given the need for long-term management of atopic dermatitis, how can you actually prepare patients for that ongoing treatment while balancing those expectations and adherence challenges?

Dr Swanson: Going back to the treatment options, I totally agree with Dr Lio, as I typically always do. We have a wealth of options, and that is wonderful. It does make our visits a little bit longer and a little bit more complex, because I really like my patients to know all the options that are available for them, given their age primarily, and then their severity of their atopic dermatitis. I actually write them out and I go through them 1 by 1 and pros and cons of each 1, and I hold them up on a clipboard so they can see the names of the medicines, because all of these words are foreign to them.

That is how I do it in treatment or in clinic. Now, if a patient and their family selects a systemic agent, let us say the only 1 approved under 12 is dupilumab, let us say I am seeing a 5-year-old and we make the decision to start dupilumab. One of the most common questions is, how long is my child going to need to be on this medicine? I say it is a bit open-ended. I would say it depends on the patient.

If I am treating a 55-year-old man that has had eczema his whole life, he has probably not coming off therapy because it is unlikely that he will outgrow the disease state at that point in his life. However, a 5-year-old, completely different story. They could outgrow it. It could become more mild. We are going to treat them with this medicine and get them better, and we are going to keep them better for a little while then once we feel confident with that, we will start increasing the time between the S-H-O-T-S to set the stage and test the waters to eventually go off of it. That is how I approach that question in the office. It is a very common question.

Wendy Smith Begolka: Dr Lio you have anything to add to that?

Dr Lio: No, I think beautifully put, including spelling out s-h-o-t-s that is my favorite, Dr Swanson.

Dr Swanson: Never say the word shot. Never do it.

Wendy Smith Begolka: Now, we are ready to pivot to our next presentation, which will be Dr Swanson on the collaborative, patient and caregiver-centered approaches to managing pediatric atopic dermatitis.

[00:51:26]

Poll 5

Dr Swanson: Let us start with a poll. Which of the following is a myth about atopic dermatitis action plans and disease triggers in children?

1. An effective AD action plan includes clear instructions for daily maintenance, flare management, and identification of individual triggers;
2. Common triggers like heat, sweat, and allergens can vary in severity and relevance between pediatric patients;
3. Although triggers can vary from patient to patient, standardized action plans can be applied universally without personalization.

Which 1 is a myth? I will let you guys choose. I feel like we can close it. The poll shows, wow, look at you guys. 100%. Way to go. Love that. You guys did a good job answering that question. You guys are learning stuff tonight. I am so proud of you. Most of you got it right.

[00:52:40]

Assess AD Severity

Let us talk about assessing atopic dermatitis severity. When I see a patient in clinic, I am taking a lot of things into account as I consider what severity of atopic dermatitis they have. Something I like to say, mild atopic dermatitis is easy to pick out and easy to identify. Severe atopic dermatitis is easy to pick out and easy to identify. Moderate is an ambiguous gray area where a lot of things factor in. A, the severity of, the overall extent of body surface area-wise, B, the impact on the patient, C the chronicity do we see lichenification, are we seeing pigmentary change, and D, prior treatment failures. All of those things bundle up in that moderate section and put patients either on the mild end of that or the severe end of that. For mild to moderate atopic dermatitis patients, I emphasize the importance of sensitive skin care, our nonpharmacologic measures, and I optimize topical therapy to see if we can get control of it.

In patients that have moderate to severe atopic dermatitis, I am again making sure to talk about nonpharmacologic and topical options, because it is important for families to know everything that is out there, and sometimes you are surprised. Sometimes you think a patient is clearly heading towards systemic therapy, then you do a last-ditch Hail Mary in the topical realm before you move on, and bingo, it is perfect for them. I think it is important to really think through that. We have these wonderful systemic agents, but some of these patients, you would be surprised, can get by with some optimized non-pharmacological and topical options. Then, if you are still struggling, you think about systemic therapy.

What I tend to do in clinic, I am an option giver. I give people all of the options, anything that they meet criteria for in terms of their age and the severity of their eczema, I am going to tell them about it. I am going to tell a patient about systemic therapy, even if I feel like at that point in time, topical therapy would probably do a pretty good job. I am still going to tell them about systemic therapy, because everybody is different in their patient preferences and their personal preferences, and it is important for them to know all the options that they have available, because there are so many.

[00:54:55]

AAD 2025 Guidelines: Baseline Therapy for AD

We have so many now that we needed updated guidelines, and we got them. We needed them, and we got them. From the American Academy of Dermatology, these are the 2025 guidelines for baseline therapy for AD and ongoing management, which we will get to in the coming slides it has been a long time since these guidelines were updated. I think the last time they were updated, Mel, the Golden Bachelor, was in high school. Just kidding. It probably was not that long ago, but it has been a good 10, 12, 15 years. So we needed new guidelines, especially with all the new medicines that we have. We still want to go over baseline management. We want to assess disease severity. We want to assess quality of life and burden of disease.

We want to emphasize the importance of identifying any known allergens or irritants that are contributing to the thing. I talk about this stuff all day, every day in clinic, and I tell people about sensitive skin care all day, every day. Sometimes I think maybe I will skip that step, either intentionally or unintentionally, or maybe the patient tells me they have seen 18 other clinicians so I feel like, ok, I probably do not need to go through the song and dance of the sensitive skin care. Then, occasionally, lessons are taught to me in the clinic.

I had a patient the other day that was not responding as expected, and I was like, ok, wait, let us back up. Let us break down sensitive skin care. It turns out they were using a laundry detergent that is a notorious aggravator for atopic dermatitis. It is important to go back to basics. Even though you have talked about sensitive skin care for 18 times already that day, it might actually be the first time somebody has really gone through that with the patient and their family. Emphasizing the role of moisturizers and emollients, I tell families with atopic dermatitis, there are 2 things that cause eczema. One is that our skin is our barrier in kids and people with eczema, their skin barrier does not work as well as other people, and they have skin barrier dysfunction. We help manage the barrier with good moisturizers, emollients, and sensitive skin care.

The second part of eczema is that it is due to too much inflammation in the skin, and it is the inflammation that causes the itch and the rash. There are some kids out there where just optimizing sensitive skin care does the trick and they are great, and they are golden, like the KPop Demon Hunters say they are golden. But then most of the patients I see, at least they are doing all the sensitive skin care. They are still not achieving the outcomes they want, then it is time to think about some treatments to help impact the inflammation in the skin.

[00:57:31]

AAD 2025 Guidelines: Topical and Maintenance Treatment for Mild to Severe AD

Going on with the AAD guidelines, it goes into topical and maintenance treatment for mild to severe atopic dermatitis, and it talks about all of our topical therapies. We have got topical steroids, which are cheap and are effective, but you have to make sure that you are using them appropriately. We have TCIs that we have known for a long time. They came out about 25 years ago. We have crisaborole, which is a topical phosphodiesterase 4 inhibitor that came out in 2017 and was a little bit of a negative experience for a lot of us. It really burned and stung like crazy. It did not seem to work all that well.

The crisaborole experiment was a little bit of a negative 1. The 1 time I will still use crisaborole is that it was studied as twice-a-day maintenance over a year for patients with atopic dermatitis, and 83% of them did not have to go back to topical steroid use for a year. That is cool. If you are using it for maintenance, it is much less likely to burn and sting.

Then we have our 3 new and novel topical nonsteroidal, topical ruxolitinib, which is a topical JAK inhibitor, which tends to work very quickly and very well. Imagine the speed and overall efficacy of a topical corticosteroid without being a steroid, so that is pretty cool. We have topical roflumilast, which is a phosphodiesterase 4 inhibitor. It is applied once a day at bedtime as needed.

A couple of cool things about roflumilast. Number 1, it is a phosphodiesterase 4 inhibitor do not judge it based on the crisaborole experience. This is its own. It is its own entity, you guys. It is its own person. Roflumilast, they really did a really good job formulating the vehicle. Very low rates of burning and stinging with roflumilast. Another special thing about roflumilast was that in the studies, once patients were clear, they had them use it twice a week for prevention and maintenance, and 57% of patients did not have to go back to daily use for a year.

That is pretty cool, too. Then we have tapinarof, an aryl hydrocarbon receptor modulator, topical non-steroid applied once a day at bedtime as needed. It is pretty cool too because it is naturally derived. You heard me right, naturally derived. Its origins come from the guts of worms. From worm poop to topical therapy for atopic dermatitis. We are thrilled to have it. It is nice to have all these choices.

It is a lot of choices, but everybody is different each of these options has its place. You can see a conditional recommendation for wet dressings. I think because our therapies have gotten better, we are just leaning on wet dressings less. It does not mean they are bad, but we are just having to lean on them less. Then, we are looking at maintenance therapy. The roflumilast was actually studied as part of a maintenance therapy. We like that. Things like ruxolitinib and have not been studied that way, but I heard from a little birdie that maybe they are thinking about it.

If you do your best: you are talking about sensitive skincare, you are optimizing topical therapies, and you think that they are using them, and that patient is not getting better, at least put your brain through the paces of, am I confident this is AD? Because sometimes there are masqueraders. Things like contact dermatitis, things like CTCL, things like psoriasis even, can be misdiagnosed as atopic dermatitis. Definitely let your brain think about what else could this be? Maybe do a biopsy if you have any concerns or thoughts about that.

[01:01:02]

AAD 2025 Guidelines: Systemic Therapies for Moderate to Severe AD

Now, if you are doing all that and you have double checked your diagnosis and you are spot on that, it is atopic dermatitis, and they are still not better, then it is systemic therapy time. Dr Lio reviewed all of these so nicely, and there is not much more to add. I think the 1 cool thing about dupi is that we have so many long-term studies about its potential impact on the atopic march. Its potential impact on growth. Its potential impact on potentially even encouraging kids to outgrow their atopic dermatitis when it started early. We have data from dupi simply because we have had experience with dupi over the past 8 and a half years, and dupi changed the world.

I think of my career as BD before Dupixent and AD after dupilumab because it is so much changed the world. In fact, when I think about dupi, there is 1 song that plays in my head and this is 1 situation where it is not my beloved Taylor Swift, that song is My Life Would Suck Without You by Kelly Clarkson, because dupi changed the game. Thinking back to the days before we had dupi, they were sad times.

The 1 other thing I want to call out with nemolizumab or IL-31 inhibitor. Nemo, is the least ouchy s-h-o-t in the world. It literally does not hurt, and it starts out with monthly dosing. As Dr Peter Lio said, can be spaced out to every-2-month dosing. That is awesome. That is 1 really nice thing about nemo, is that it really does not hurt, and we love that for our patients.

We see a conditional support of our systemic immunosuppressants. I have become a bit known for saying that picking a systemic agent before we had wonderful options in our toolbox, like dupi and others, was like picking a porta-potty out of a row of porta-potties. You know they are all going to suck, but you have got to pick 1 when you have to go.

I was never excited to put a patient on methotrexate or cyclosporin. I did it out of desperation because I had no idea how else to help them. Now we do not have to pick a porta-potty anymore. We see this recommendation against systemic corticosteroids. As Peter Lio said, this just aggravates the problem. It just fuels the fire. Do not use systemic corticosteroids. I think we leaned on them in the past because again, we did not have as many options, but we do not want to lean on them now. We do not need them anymore. We have so many good things.

[01:03:27]

Pediatric AD Action Plan

In the olden days, meaning more than a year or 2 ago, a lot of people reviewed this pediatric AD action plan with their patients. What to do in a green time when things were actually looking pretty good, and you are just doing gentle daily skin care? What to do in a yellow time when you are starting to have a little bit of a flare, and what topicals you would want to implement. And then what to do when it got really bad, and you were in the red phase. Taylor Swift she has a song called Red. If you are in the red phase, what do you do in that situation?

I think it would be interesting to see if people are still utilizing this now because again, our option lists are so much greater. I do not know how much the green yellow red is utilized today, but I think any system you have to convey these action plans to your patients use that.

[01:04:08]

Available Topical Therapies

We have already reviewed these topical therapies. I think we covered all the high points with these. It is really nice to have so many topical options, especially that are non-steroidal. We are grateful for that.

[01:04:18]

Systemic Therapy Considerations

When you are thinking about a systemic therapy, there is a lot of things that bundle up in that consideration. What is their atopic dermatitis phenotype? Do they have eczema psoriasis overlap? Do they have facial predominant eczema? What is their phenotype? Do they have a prurigo nodularis type phenotype? So, getting to the bottom of that, because some of our different therapies work better for some of those different phenotypes.

Patient comorbidities. Do they have asthma? Choosing dupi would help you feed 2 birds with 1 scone. We are not killing birds with stones anymore. We are feeding birds with scones. It’s PETA approved. If a patient also has alopecia areata, I might consider an oral JAK inhibitor because it can treat their atopic derm and their alopecia areata very nicely. You also want to consider the risk-benefit profile of the available treatments, patient preferences, exclamation point.

That is so important to have that shared decision-making, because if you come up with a solution for them and they are not a part of that decision-making process, I think your success rates are low. I think they are unlikely to use that therapy, or utilize that therapy in the way that it is intended for them. Then drug interactions and clinical monitoring, what is their past medical history like? What is their med list like? Make sure the options available are safe options. And then access, access - always the big stickler.

[01:05:42]

When to Consider Alternative Systemic Therapy

When to consider alternative systemic therapy. When an inadequate response has been seen, at least entertain a switch. Sometimes patients are improved on a therapy. Say somebody on dupi, and they are 50% better. That is significant, being 50% better than being that bad 12 to 16 weeks ago, that is a big deal. Maybe they are a little bit nervous about making a switch because they are nervous about a backslide.

Talk to them about the options available, about how you think they stack up, and how those options are either good or bad for them. Always think about using a topical therapy until the new systemic agent is fully effective. Some patients can get off topicals eventually, but typically not at the beginning. Often, there is a little bit of an overlap period as you are switching systemic agents, we think that is ok.

[01:06:30]

When to Discontinue Biologics

When to discontinue biologics. That big question, how long will my patient need to be on it? These clinical outcome measures somewhat display that. It is a little bit confusing, I will explain. These are patients who are on dupilumab 300 mg every 2 weeks. Then they are successful on dupilumab, and they are switched to either staying on every 2 weeks, switch to every 4 weeks or switch to every 6-8 weeks.

You see actually they maintain these clinical outcome measures very nicely, regardless of if they are in the orange group, where they are every 2 weeks, the green group, where they are every 4 weeks, or the blue group, where they are every 6-8 weeks. This is how I do it. I just increase the time between the shots and see how things go.

[01:07:13]

Shared Decision-making in AD

Shared decision making. I mentioned it before. It is worth highlighting. It is everything when you are talking about atopic dermatitis, especially with the choices that we have. Listen and engage with patients and their caregivers. Hear what they have to say and what their desires and preferences are. Accommodate the varying economic and appointment needs. Facilitate closer follow-up when needed and desired, when you just feel like you need to keep tabs on them and hold their hand through it. Consider patient goals, preferences, and cultural skin care practices when you are making these decisions. And of course, this with medication access and support resources, because a medicine can be super great, but if your patient cannot get it, it is no good to anybody.

[01:07:49]

Posttest 3

We will go to posttest 3. A 12-year-old girl was recently diagnosed with AD. She is anxious about using treatments that may affect her appearance at school. Based on shared decision-making principles, what is the most appropriate next step?

1. Recommend initiating systemics to achieve rapid symptom relief;
2. Advise avoidance of known triggers and select a personalized topical regimen that aligns with patient preferences;
3. Reinforce strict adherence to a standardized treatment protocol as it is the most evidence-based; or
4. Suggest transitioning to phototherapy as it avoids systemic exposure.

I will give you a second and then let us go ahead and see the results. I bet you guys were relatively fast, and I know we are coming to the end. 97% of you guys got it right. However, there would be a part of me that would advocate for choice A, recommend initiating systemic therapy immediately to achieve rapid symptom relief. It sounds like maybe she is not super excited about topicals, and so that might be something that I would entertain too. I do not think A is entirely wrong.

[01:08:50]

Key Takeaways

Key takeaways. Atopic dermatitis significantly impairs the quality of life for both patients and caregivers. Topical therapies remain first line. However, their inappropriate use or even appropriate use can cause burdens. Newer systemic options are available for our patients. Engaging patients and caregivers in shared decision making is imperative to improving self-management, adherence, and quality of life. Develop patient-specific action plans to address barriers to care in atopic dermatitis to optimize outcomes.

Q&A

We did it, you guys, with a minute to spare. Happy to answer any questions. I know we got 1 as we were going through. Happy to answer any other questions if people have them.

[00:09:28]

Poll 6

Wendy Smith Begolka: We did and I think we have time for maybe 1 quick question, which is, are you looking at any other functional measures to help track treatment success?

Dr Swanson: Functional measures meaning like growth and school, or what are we meaning there?

Wendy Smith Begolka: Not a lot of other detail, but I think those are good suggestions to start with.

Dr Swanson: One of my favorite things to ask people when they come back and they have been on a systemic therapy is, what were you not doing before that you are now doing? It might mean swimming or playing outside because those things can be big-time irritants. It might be trying out for a sports team. It might be finally going to sleepovers because you felt too self-conscious to go before. I like to see how their behaviors are changing as they respond to treatment.