Brittany G. Craiglow, MD

You talked about staying up to date. Maybe that’s the last question that I’ll leave you on. I know it’s hard enough for all of us to keep on top of what’s going on. I can barely keep track of every new thing I hear about every day. Do you guys have thoughts on how we keep patients and caregivers up to date on emerging options? In my clinical practice, my patients love hearing about what’s coming, what we’re thinking about, and where things are headed. I don’t know if that’s discussion everyone else is having at their clinical encounters, but I imagine that when you give your patients a little insight in terms of what’s happening, they immediately latch on and want to know more. In many ways, it’s empowering knowing about their disease. I’ll start with you, Peter. Any thoughts on how you keep the patients and caregivers up to date?

It’s our biggest challenge. Even for us, staying up to date is hard, and then you’re trying to keep everybody on the same page. One thing we’re going to need to do is unfortunately we’re going to have to sift some of the wheat from the chaff. We see this. I follow a lot of podcasts and a lot of blogs, and I have all these interests. But when things get out of control and my schedule is going crazy, I quickly go through and say, “This doesn’t look that important. That doesn’t look that important.” I pick the ones that I want. It’s an embarrassment of riches, but we’re going to have to do that a little with atopic dermatitis. There are thousands of publications practically every month. We’re going to have to sort through. Groups like ICER—the Institute for Clinical and Economic Review—are cold and calculating, and I don’t necessarily love their approach, but I’m grateful for it when they hard-and -fast say this is the one that seems to work the best, these are the ones that are most economic. We can target our focus and attention, which is a finite resource. We don’t have the ability to learn about everything.

It’s also going to happen from us too. We’re going to have to learn these things the hard way, and then hopefully we can pass on our wisdom to our colleagues so they don’t have to go through it. A word to the wise should be sufficient. We can say, “This one is probably not worth your time. This seems to be the better approach.” That’s not perfect. We’d love for everything to be balanced and equal and potentially have opportunity, but there isn’t enough time for everyone to explore every option.

How about you, Brit? Same question. How do you foresee, or in your own best practice, keeping patients and giving up to date on everything that’s happening?

I agree. It’s tough. I learned today from you guys, and I like to think that I’m fairly up to date. It’s hard, especially if you’re more of a generalist, you’re seeing a million things all day, and you don’t have a ton of patients with atopic dermatitis. For us, it’s nice for patients to hear that people care about the disease they have and that we’re working on it and constantly refining treatments. Hope is a very powerful thing and really important for people. Even in diseases where we don’t have as many options, letting people know there’s stuff in the pipeline, we’re moving, keep your eye on the news. These things, if they do well, tend to make a splash. For us and our colleagues, watching things like this, going to meetings, and looking at the throwaways, all those things can be helpful.

If you have a patient and you’re stuck, that’s a time when you learn. If I have someone and I feel as if I’ve reached the end of my options going through the literature, doing a PubMed search or seeing if there’s anything new or if there’s a report [is helpful]. When you can tie your knowledge to a patient that it sticks. We remember from med school and residency, when you had a patient with a certain disease, all of a sudden you remember it. If we’re caring about our patients and we’re striving to always do our best by them, then if there’s something you don’t know about and it would benefit your patient, you’re probably going to find it if you’re looking. If your patients are doing well, cool. But if you have someone who you’re stuck on, maybe phone a friend or ask Google, and you can get information.

You highlighted one important thing. In the age we live in, everyone wants digital content, everyone wants social media, people want things that are short, people want stuff that gets to the point. Discussions like this help our providers. One can envision similar things with patients and caregivers to give them a voice, give them evidence-based solutions, and go away from some of the mixed evidence-based stuff out there, in terms of conventional social media outlets, that we sometimes have to deal with when patients come to our offices.

It’s rare that a TikTok [video] makes people come in for the right reasons. I’ve had it happen before, but sometimes it’s very mixed. Bottom line is that thinking about ways that outside the office we can increase the education of everyone coming in is going to make that discussion much richer and empower our patients and caregivers.

On that note, that brings us to the end. Dr Brittany Craiglow and Dr Peter Lio are superstars. Thank you so much for this informative discussion. It’s been a pleasure to spend this time with you guys, and I thank you all for watching this 

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Experts in dermatology stress the importance of patient education in atopic dermatitis management and discuss their approaches to keeping patients up-to date.

The Importance of Patient Education in Atopic Dermatitis Management

In the last few minutes of our discussion, I want to talk about what’s coming and future directions and hear from the experts on the panel about what we all want to see when it comes to our patients with atopic dermatitis [AD]. I’ll start by saying we spent a little time touching on crisaborole, which is a PDE-4 inhibitor, as a potential mechanism. After about 5 or so years on the market, reception has been a bit lukewarm in the sense that efficacy hasn’t necessarily been outweighed by the number of patients who experience some degree of cutaneous sensation issues, whether it’s stinging, burning, or whatnot. For a while there was a thought about whether PDE-4 is the right target for atopic dermatitis. Is there something else we should be thinking about?

There’s been a bit of a flurry of activity with a couple of medications. There’s roflumilast and difamilast, both of which are moving through clinical trials that are showing that PDE-4 inhibition might be a reasonable and good strategy for patients with atopic dermatitis. You can potentially get even better efficacy than we saw with crisaborole, and we can also see good vehicle technology and drug technology minimizing any adverse events we thought about related to cutaneous sensation. Those are the 2 that I’m particularly excited about, especially since roflumilast is moving its way through psoriasis…in addition to atopic dermatitis. That’s going to be really exciting for all of us.

But I’ll ask you guys. Maybe we can start with Brit and then Peter. How do you anticipate the treatment landscape of atopic dermatitis going forward? Is there anything that you have your eye on that you think is going to be big? Is there something you want to see that you’re not seeing in the development landscape?

More topical medications will be welcome. Personally, I’m hoping to see a younger indication for oral JAK [janus kinase] inhibitors for AD because I do think there’s a role in a younger population. There aren’t going to be a ton of kids, but we still have kids for whom dupilumab isn’t quite cutting it or the injections are so traumatic that they fall off. For me, that’s probably the most exciting thing.

I mentioned this briefly earlier, but a lot of these kids have comorbidities like alopecia areata. About 30% of patients with alopecia areata also have atopic dermatitis. We know that JAK inhibitors are useful for both diseases, so just as we’re getting asthma and AD with dupilumab, we may be able to capture multiple comorbidities with oral JAKs in younger patients too, which will be really exciting.

The more options we have, the better. It will be interesting to see in 5 or 10 years. We don’t really have biomarkers. We don’t really have ways to say if you’ll probably respond better to this medicine or that 1 because everybody is a little different. I have patients on an oral JAK inhibitor for alopecia areata whose eczema doesn’t get much better. There are different phenotypes, probably related to different genotypes, and different things going on. We may be able to personalize our drugs a little better down the road. That’s more pie in the sky. [Right now we] try this, if it doesn’t work then we try that. Maybe we’re going to be able to say, “You have these characteristics, so this medicine might make more sense for you.” That’s going to keep it interesting.

I love it. If Peter gets to insert his hot take, then I get to insert mine. I don’t know if we’ll necessarily get to one of these biomarkers and say these 3 or 4 things [will work], given the heterogeneity of the disease. Maybe it’s going to be dependent on more patient-reported, patient-intrinsic factors. When they tell us these different things about their disease, that’s how we’re going to choose, as opposed to whatever the genes in the serum say. But that’s a different discussion for a different time. Peter, what do you have your eye on? What’s exciting to you or interesting? What do you want to see happen that’s not happening?

There are a couple things. Definitely, selfishly, we love these powerful systemic agents because those are the patients we see who are miserable and suffering and out of options. But from a population standpoint, I’m excited about the topical nonsteroidal medications as well. Roflumilast and difamilast—those are exciting. With tapinarof, which is the aryl hydrocarbon receptor inhibitor, I’m interested in what they’re doing because it’s approved for psoriasis already. They already have data in atopic dermatitis suggesting remission. This is my favorite buzzword, and I want to see how that’s going to play out. I’m also interested in the microbiome. The microbiome is the final frontier. We’re outnumbered by the microbiota on our skin and in our gut. What we find in prebiotics, probiotics, synbiotics, are there going to be things that we can do?

There are a number of companies working on some neat things, including OTCs [over-the-counter medicine]. The OTC space is blowing up. Unfortunately, we don’t have the same level of evidence and regulation. From new things like topical anti-staph treatments, which use endolysins derived from bacteriophages, to pro and prebiotics, it’s amazing. It’s hard to keep up with. The level of evidence is lower, but these can sometimes have an outsize effect on patients at large because if we can prevent them from getting to the point where they need us then everybody wins.

Raj Chovatiya, MD, PhD; Brittany G. Craiglow, MD; and Peter A. Lio, MD, provide insight into emerging therapies and future directions in the management of pediatric atopic dermatitis.

Emerging Therapies and Future Directions for Pediatric Atopic Dermatitis

That was a tour de force master class on how to dose. Peter, I don’t know how you and I could follow this. I’m just going to call you if I have dosing questions. I might toss a different question over to Peter, so we don’t embarrass ourselves because that was so good. Maybe you can tell me, Peter, what do you think about long-term treatment and therapy, and what you used to do vs what you do now with dupilumab? How is this going to change in terms of chronic treatment for people with pretty chronic moderate to severe disease?

This is my hot take on this area. I think that the next frontier, obviously we want to cure people. That’s the goal. We’re ways away from that I think, I don’t think we fully understand enough to be able to just turn it off. But the next frontier is remission. So all of my energy right now is focused on, can we induce remission for patients and what treatments are better at doing this? I wrote paper a couple years ago saying that dupilumab I really think can induce remission in some patients. Here’s the idea. We talked about this vicious cycle with those 5 pillars all fueling each other, no matter where you start, you’re getting barrier damage, inflammation, nerve-ending changes, microbiome dysbiosis, and of course, neurobehavioral issues. If you get things under control, then the barrier gets stronger. The microbiome normalizes, the inflammation calms down, the nerve endings morphologically and physiologically go back to normal, and the behavioral cycles go back to normal. Thus that vicious cycle goes to a virtuous cycle, and it follows that we should be able to pull back.

Now, not everybody, I wish everybody, but in some patients I’ve been able to successfully stop dupilumab and follow them for many weeks and even months after. We know it’s in your system for maybe 8 to 10 weeks. So this is long past when there’s any trace of the drug in the system. In this report we did, not a single patient had a rebound, so that’s part 1. We know with prednisone or prednisolone, we expect at least some of those patients to have a big rebound spike, worse than their baseline. Not a single patient in our cohort got back to their baseline, even over all those months after. I call this a relative remission, and I think that is my next frontier.

What I’m doing now is I tell patients when they say, “Is this forever? Is this like a blood pressure medicine or diabetes medicine?” I say, “No, not necessarily. I’m not going to make a false promise and say definitely no, but not necessarily. Our goal is to get you better for a period of time.” I usually define that as 6 months to a year. If they’re doing great for that longer period, and I really feel like things are back to normal, I think it is reasonable to start discussing either pulling back or spacing people out. We know some of the newer medicines, in fact there is a newer biologic that only has an indication for adults. It has a secondary dosing regimen that spaces it out to once monthly if they’re doing well. I think we can take lessons from that and use it for our other medicines, or even stopping completely and going back to other things we did leading up to it. So going back to topicals or maybe going back to phototherapy, things like that. I do believe that for at least a substantial portion of patients, we’re going to be able to get them in that remission state.

A hot take indeed. But I think that we all agree that remission is something we all think about, of where can we get people to the point where we don’t have to burden their lives so much in terms of the treatment they use. You highlighted a very interesting point. They did this, even though it hasn’t been highlighted, in the case of dupilumab compared to tralokinumab where there was a phase of the trial where they took people from 2 weeks to 4 weeks, and a good chunk of people do end up holding before falling back. I think there’s so much heterogeneity with the disease, it’s going to come down to, like what you said early before we talked about all this, patient selection is going to be key for everything when it comes to our atopic dermatitis therapies. Maybe this is where the real proof of matching the right patient to the right treatment is going to work out. I think that’s going to be the most interesting thing we all work on over the next decade.

I’ll leave you with 1 more question, Peter, it seems like given safety, efficacy, the ages of approval, dupilumab seems to be a very feasible and real treatment that can be used in the long run for many patients. Are there medications you would not use or you would have more caution for as a chronic treatment for your pediatric patients with atopic dermatitis, some of the other options we talked about that you might use a little differently compared to dupilumab?

Definitely.I feel like if we have to go long term, and I’m defining that over years, more than a year or two, I do feel that our biologics are probably the best bang for your buck. They’re more likely to be safer in the long term because we have longitudinal data; we have 3-year, 5-year, and even some 7-year data that are already being published. That’s exciting stuff, that helps me. For our broader immunosuppressant agents, for example, cyclosporine, a great drug for many patients, but it’s not optimized for long-term use unless you are up against a wall. Typically I take the recommendation of PeDRA [Pediatric Dermatology Research Alliance], which years ago made that point. We try not to keep people on it for more than a year. My goal is 6 months and I want people already coming off, sometimes even 3 months if they’re doing well on cyclosporine. I want to be thinking about other options. Obviously, prednisone, we talked about it, I wouldn’t want to do that for more than little bursts if need be. Same for methotrexate, 1 to 2 years of use at most. Mycophenolate, in the right situation, may be the safest of the traditional ones, so maybe a year or two. But again, with long-term immunosuppression, we see all of these risks.

Now, our JAK inhibitors, where do they fall? My sense is that I would prefer to minimize them when we can. I think a year or two would be a reasonable time to think about other options for most patients. But that being said, as we’ve heard today, for some patients, these really are the only thing that has worked or the most dramatic thing. I don’t want to take that away from a patient. I’ve already had a patient, all of us I’m sure have started people on JAK inhibitors before they were actually approved. So we have people who are now on it for a year or two. I have an older gentleman who I keep asking, “Can we come off of it? Can we tinker with it?” And he says do not mess with it. He’s like, “I’m living my life the best ever, my blood work is fine, I feel great, please, don’t tinker.” You know what, I say OK. I don’t want to push him. So he is kind of a long-term user of an oral JAK inhibitor, and thank goodness he’s doing great. I hope it stays that way.

I think for most patients, I’m going to try to at least start planting the seeds. Can we think about coming down? Can we do other things? Even if it’s rotational therapy. In the old days, for psoriasis, that’s what people used to do. Maybe you would do 6 months or a year on one, take a break from that and try something else for a while, and then we can always go back to it. I like to give the body a break.

Dr Peter A. Lio hypothesizes about the ability to induce remission in patients suffering from atopic dermatitis with the use of biologics and holistic treatment approaches.

Evolution of Treatment Selection for Pediatric Atopic Dermatitis Management

We’ll get into the weeds here a bit, and I know that you can probably say this like the back of your hand whereas the rest of us can’t, you can talk about some of the nuances and differences in dosing of dupilumab across the age groups we’re thinking about. I know oftentimes we have a very adult-centric view of things, but the actual regimen does change a little below the age of 18.

What I tell people is that you can always look it up. You need to make sure if you don’t treat a lot of children, and you’re not used to doing a lot of weight-based dosing, you can always look it up, but you also need to have a scale in your office. You can’t be trusting patients for their weight. You said something before, children aren’t just little adults, and it’s true they really aren’t. But with Dupixent [dupilumab], aside from the dosing and aside from thinking about vaccines and the younger patients, it’s really not that different. People who are worried about treating children, or maybe you see them in your practice, but you’re not sure if you can pull the trigger on this—if you can do it in adult, you can do it in a child. You can feel empowered, it’s OK. Like we said, nothing came up different in these groups in terms of adverse effects. It’s a very similar conversation, etc.

For the dosing, if you’re 18 and over, you get loaded with 2- 300 mg doses, and then you get 300 mg every 2 weeks. Once you hit 12 years old, if you’re 60 kg or more, you get treated like a grown-up. You get the same dose. As a side note I will say that if you have asthma and you’re 12, you get treated like an adult no matter how much you weigh. In my children with concomitant asthma or who are near 60 kg, I try to get them the higher dose when I can. Remember, children are always growing. If they’re on the brink, sometimes I try to get them on the higher dose because they’re going to be there in 6 months anyway.

In your 6 to 11 age group, if they’re 60 kg or more, they’re adults, so it doesn’t matter. The cutoffs are 30 to 60 kg. They’re going to be getting the 200 mg dose, but they’re still going to load with 2 doses, and then they get 200 mg every 2 weeks, so the same schedule. Then the next cutoff is 15 to 30 kg patients, these are your early elementary school children usually. What’s a little surprising for people is they get the same loading dose as an adult. So they get loaded with 600 mg, but they don’t get redosed until 4 weeks later. So they get 300 mg monthly. When the indication came out I was so excited because they had done Q every 2 weeks and Q4 weeks in the trials, but when data came out showing Q4 weeks was a little more effective, and had a little better safety, so that was what came on the label. I’m telling you, 12 shots a year we can do. Twelve shots a year is way more doable than 24, and this is something that makes it so the needle is almost never a deal breaker. I’m not saying the children like it, but it’s doable.

Now that we have the 6-month to 5-year-old indication, we have another weight range, which is less than 15 kg. What’s really cool about this age group is there’s no loading dose. You just start with either 200 mg if they’re less than 15 kg, or 300 mg if they’re 15 to 30 kg. Then you just go every 4 weeks. Again, you don’t have to memorize it, you can always look it up.

One thing to note is that as of now, the pen is only approved for ages 12 and up. We only have the syringe for our younger patients. Anecdotally, I have patients who have used both; most of them tend to prefer the syringe. You have a little more control over it, it goes faster. If you do use a pen, you have to know you have to hold it down. If you’re going to do it and teach them with a pen, you want to hold your hand with their hand while they do it because the instinct to lift up is very strong. Another practical note, for children who do get the loading dose over 6 years old, oftentimes what I’ll do is, my nurse will take 1 leg and I take the other, and we do it at the same time. Because I think there’s nothing like giving a child a shot, and then saying now you get to do that again. Sometimes that means I have to come back for teaching with the parent to do it, but I think that makes that initial encounter a little easier for everybody.

Dr Brittany G. Craiglow reviews dosing considerations and nuances for the use of dupilumab for atopic dermatitis in pediatric populations.

Brittany G. Craiglow, MD

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