Vivian Shi, MD, FAAD

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In this MEDcast episode,Raj Chovatiya, MD, PhD, and George Han, MD, PhD interview Vivian Shi, MD, FAAD, to discuss the latest clinical evidence on the management of atopic dermatitis (AD) in different age groups and patient factors to consider when selecting a treatment for AD.

Management of Atopic Dermatitis in Pediatric and Adult Patients

 We’re going to play a little game. I’m going to put each of you on pro and con. You’re in the camp for biologic therapy vs the situation that you may not want to. I’m going to give you the con position, Vivian. What are the circumstances in which biologic therapy would not be the right decision for your younger child when you’re trying to control their atopic dermatitis? Let’s say this is an infant, a toddler, or a very young child.

 The label is the biggest con. It’s not approved below age 12, so we don’t…know how to dose it. That’s 1 of the barriers. With JAK inhibitors, there’s a requirement for lab monitoring for individuals. Most children are healthy and don’t have the comorbidities that we’ve seen in some of the postmarketing studies that led to the box warning, but we need repeated needle sticks to see laboratory changes if they’re ordered too early. Most of them will return to baseline and are clinically insignificant. It can give a little high blood pressure for both the parents and the prescribing provider.

 I’m making her scrape the bottom of the barrel because we all figured out that there are mostly advantages. I’ll put you on the other side, George. In the pro column, if I’m a parent with a young child, what are the top 3 or 4 reasons why your infant with moderate to severe disease needs biologic therapy?

 Right off the bat, it’s that track record—hundreds of thousands of patients, multiple indications. It’s reassuring that you’re not the guinea pig. You’re not the 1 testing this out for the first time. Then they need to step back and think about how this disease is affecting other areas of their lives, like embarrassment and normal social development. These are all things that they might not be talking to their parents about, but they’re definitely experiencing. That’s part of it. The compliance is important: what a teenager can be bothered to start ointments? I’ve been surprised. For some of my patients, I start the discussion by painting a full picture of what’s out there. By the time they get to us in our academic centers, they’ve usually been through a couple of offices. They’ve seen their primary care provider. They’ve been on different things. They come in holding the bags of various antifungals, steroids…

 Maybe there’s voodoo witch magic. It’s nice to set the tone and say these are all the things. I’ve been surprised by some of my patients. If I’m looking at them, I don’t think they want to go on a biologic, but then the moment I say it, they’re like, “You mean I could do an injection every 2 weeks and not have to smear these ointments all over and worry about greasing up my clothes and my sheets? Give it to me. Why am I not on it already?”

 I’ll add another pro. For dosing patients who are that young, plenty of them are going to be once every 4 weeks instead of every 2 weeks. It’s a matter of prepping for that 1 dose. I love how you highlighted this idea of adherence and compliance. We get so caught up in safety and efficacy that we forget the other part of the discussion. Is it something patients are going to want to use? More important, is it something people can get? Access is another part of it. My experience is that there’s a broad range of pluses and minuses when it comes to getting the therapy I want for my patients. I’ve been empowered. We’ve been doing many things off-label for so long. There’s no reason we shouldn’t be using medications that are approved for their indication instead of wasting time with anything else. That’s my biggest feeling. I tell my patients that I’ll go to bat for them as much as I can to make sure that this is the right therapy, and that’s what we’re going to do. It’s important to support our patients through this journey, because it’s complex when it comes to thinking about advanced treatment. We need to make sure they’re getting access to a patient-assistance program and that there’s help in terms of ambassadors or other support. It can be a lot, no matter what the age group is. Have you faced any specific challenges for your patients, Vivian? We’re all in different academic centers and places, and you and I have talked about some of your specific access challenges before.

 It’s definitely academic center and state specific. I’m in Little Rock, Arkansas. My institution is the only academic center in the state. The majority of my patients are on Medicaid or Medicare. Access is not great for Medicaid in my state. I joke because the coverage for Medicaid changes if you live in a border town—you could move across the border and coverage for that biologic might change right away. I’ve had patients move 10 minutes across the state line to get access to their systemic medications. A biologic coordinator or a clinical pharmacist is so important in an academic center.They work with a specialty pharmacy. It’s true. My clinical pharmacist is the best-kept secret of my clinic. I can’t imagine running an eczema clinic without her.

You mentioned patient-assistance programs. It’s important to get in touch with the local pharmaceutical rep and continually check out the criteria for eligibility. A few years ago, we published a paper on a patient-assistance program for different pharmaceutical companies. If I looked at the next month, the criteria would change. I said don’t get beat up because it was denied initially. Keep checking.

 Get everybody enrolled no matter what, whether it’s through an online portal or a form. There’s no way you can investigate benefits and figure out if there’s anything that can help your patients unless you try. There’s billions of dollars pumped into this for assistance. It’s there, and it’s a huge untapped resource for a lot of patients who feel they can’t get therapy.

 It’s so important. That’s the other piece of having more medications available: there’s more competition and more pressure on companies to do better with their access programs. One clinics I work at with my wife is underserved—about half our patients are uninsured—and the joke is that it’s better because there’s no formulary to follow. We just pick the right medicine and apply it to the patient-assistance program.

 That’s an interesting way to look at it. I have different challenges than Vivian. In my population in downtown Chicago, I do have a good chunk of commercially insured patients, but I also see a lot of Medicare patients. With Medicare criteria, you often run into all sorts of things that you may end up getting approval for. But the out-of-pocket cost is so high that when you hit that not-sweet spot, it’s unaffordable. They earn a little too much to be in the assistance program. This is the bane of our existence, and it’s something I’m constantly thinking about. For anyone listening, this is 1 of the areas we need help with the most. That’s not a challenge unique to me. It’s 1 we all face.

Thank you for this rich and formative discussion to all my colleagues, George and Vivian. Thanks to the audience for tuning in. If you enjoyed the content that we were talking about, please subscribe to our e-newsletters to receive upcoming 

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Videos

Drs Raj Chovatiya, George Han, and Vivian Shi review the current challenges and opportunities surrounding the utilization and availability of biologic therapies in atopic dermatitis.

Challenges and Advantages in Use and Access to Biologics for Atopic Dermatitis

 To revisit an earlier issue, we talked about some exciting updates with biologics, where we have drugs that have a favorable safety profile and approvals going down all the way to the youngest children in infancy. A new question in my mind, for children that young, is how do you figure out that they’re the right patient for biologic therapy? Because you have several new challenges in that pediatric age group. It’s about not just the therapy working but also all the external factors—giving a shot, making sure there’s adherence, etc. Do you have any thoughts on that, George?

 It’s for the little children. I don’t think we’ve captured enough of what this disease process does to them globally. I have atopic dermatitis [AD]. My older daughter does too. But my younger 1 doesn’t, and she’ll absentmindedly start scratching. I wonder about the attention span of children being able to focus and concentrate on things with atopic dermatitis distracting them.

 We don’t have a good grip on the cost of not treating them well. For those patients who go through the emollient, if you’ve tried the short-term potent topical steroid therapy regimens and they aren’t turning around, there’s not much reason to hesitate. The biggest holdup I have for younger children is that parents ask, “When can we stop?” To some degree, this is something everybody asks. I tell those patients and parents that we hope that your child will outgrow this. In many cases, that’s possible. I don’t want to put you on a medicine that you don’t need. That’s the last thing I want to do. But we have to do it together. We come to an agreement and say that if they’re itch-free and rash-free a year or 2 from now, then we’ll gradually back off in the hopes that we can eventually get your child off the medicine. That helps persuade patients to get on because they’re scared of that commitment. Even though we think these are very safe medicines, and we have good data across many years, these are their children, so parents get apprehensive.

 In the opportunities I’ve had to push that age limit down, I’ve highlighted that the greatest risk is not treating the disease. Based on a lot of that data, that causes folks to revisit whether they truly feel that they’re a good candidate for the medication. Whatever needle phobia or general medication phobia exists ends up largely disappearing. Has your experience been like that too Vivian? Do you have any challenges in figuring out the best time to recommend biologic therapy for your younger pediatric patients?

 It’s a lot harder for parents to keep a child on topicals day after day, year after year. Just like for the adult age group, my recommendation for going systemic is when topicals are not adequate or impossible. For impossible, imagine an active squirmy toddler or baby. Topicals are particularly burdensome for them. Providers don’t talk about the cream burden enough with their families. If a child splits their time in more than 1 household, then the regimen complexity multiplies.

I completely agree with George that inadequately treated children with AD could have profound disturbances in their physical and mental development with more mood issues as they grow up, more behavioral issues like attention deficit disorder, and difficulty in school performance and extracurricular activities. I have a lower threshold and start talking about systemic treatments, but we also don’t involve children early enough in the shared decision process. Of course, you can’t involve a 6-month-old, but when my son was 10 months old, he had a preference for eczema cream vs ointment even before verbalizing it. Involving the children early on in shared decision-making is paramount because they’re going to grow more confident with the treatment they’ll be on for longer as they grow older and probably will have less of that false expectation that they’re definitely going to grow out of their eczema and get better over time. Learning early is better preparation for the longer term.

 Arming yourself with the data is the most important thing. Parents often have more questions that the adults you’re treating. They’ll say, “Give me the numbers. Does this work? What does that mean? Is this safe?” Looking at a few figures published 

 in 2022, this was the phase 3 program that looked at individuals 6 months to 6 years. The data at week 16, looking at patients who were clear or almost clear for biologic and nonbiologic, was almost 30% vs about 4%. You’re thinking about multifold more individuals who were treated with the biologic therapy, with the active getting better and a similar rate of adverse events, 60% to 70%. The worrisome adverse effects that you might think about were quite low and consistent with every other trial seen at adolescence, adults, and any other trial program. There’s some value in figuring out how to contextualize those numbers in ways that are easy to understand and that drive home that point. Are there any tricks that you picked up when you were trying to take complicated trial data and make them approachable? As a parent, you’re worried about your kid, and you want to make the best choice.

 It’s even harder to explain these clinical trial data to other physicians. We have to keep in mind that the point of a clinical trial is to prove the medicine is superior to placebo; that’s it. It’s not meant to say in what cases a treatment is a success. It’s interesting that individuals have taken treatment success in a controlled clinical trial to mean success in treating in real life, because that’s not the case, especially if our measures are a little imperfect.

I see it both ways. If you tell a patient the chance to get almost clear is around 30%, then they’re going to be say, “There’s a 70% chance of my child failing this medicine?” That’s where the real-life experience comes in: almost everybody feels so much better. The time it takes for the skin to clear might lag behind that a little. Occasionally they’ll still be itchy, and you’ll still need to moisturize them, but their quality of life is going to be much better. That’s the tough part when we look at the AD trials. It’s difficult enough to compare trials in something like psoriasis, which is more monomorphic. In AD, they’re all over the place. We need to point that out—it’s much better than placebo—and emphasize that the safety looks very good. It’s important to give them real-world experience of patients having their lives changed by this medicine.

Expert dermatologists highlight the burden of atopic dermatitis in young children and examine the clinical data for dupilumab, a biologic treatment for this age group.

Considerations for Biologic Treatments in Pediatric Patients with Atopic Dermatitis

 Maybe you guys feel different, but I’m figuring out how to balance these therapies across children, adolescents, adults, patients with more severe disease, and patients in that moderate range. What’s the best choice for them? You both highlighted 1 important distinction between some of them: age cutoffs. In the case of dupilumab, we’re talking 6 months and up. In the case of tralokinumab, it’s 18 months, but it will probably soon be lower. In some other markets, there’s adolescent dosing as well. In the case of oral JAK inhibitors, both are down to 12 years and up. In the case of our topical therapy, 12 years and up. There are many choices. It’s becoming harder to parse out the right circumstance to use these therapies for the right patient. George, how do you figure out the right treatment and the right patient? That’s a billion-dollar question.

 It’s tough, but it’s interesting. With psoriasis, you have this luxury—at least in clinical trials—to exclude unstable forms of psoriasis. We exclude guttate psoriasis or erythrodermic psoriasis. How do you handle it when your baseline disease state is unstable to begin with? That’s the tough part, especially when you have patients who come in and don’t have severe eczema all the time but have bad flares over the course of a year. It’s been a struggle for me to convince patients that they need to be on year-round therapy for something they see as more episodic.

One of the challenges with biologic therapy is that the rates of antidrug antibodies go up the longer you stay off these medicines. I’ve seen some of my patients who, during COVID-19, went off a biologic for atopic dermatitis. When they tried to go back to it, they got less of a response than they had the first time. That’s 1 case where if you’re looking for a biologic and the patient still wants a biologic, another medication such as tralokinumab could be helpful.

It’s interesting that we’re at the cutting edge of immunology and dermatology with these medicines. We’re learning things about the decoy receptor and tralokinumab blocks. There’s so much interesting science behind all these developments. We’re still constrained by our clinical trial outcome measures and the time we can keep patients on them. Medicine like tralokinumab needs a little longer to get up to full efficacy, but you can’t keep patients on placebo for more than 4 months, or 16 weeks. That’s the practical side of trial design. There’s a lot of nuance that we’ll hopefully figure out even with new biologics coming out. I still mostly place my patients on JAK inhibitors or patients who haven’t done well on dupilumab. That doesn’t just mean somebody who’s totally failing. There could be improvement in a large part of their body surface area, but there are some stubborn areas, often on the head and neck, where they’re not doing so well. They might be looking for another option to carry them the rest of the way.

 I like that because I feel that we’re constrained in some ways. It’s great that we have so many trials, but we think about atopic dermatitis relatively homogeneously in terms of the way we design our studies. That million-dollar buzzword is 

. If we’ve learned anything about the biggest differences between our 2 common diseases—atopic dermatitis and psoriasis—it’s that psoriasis is much more predictable in many ways. It’s a single linear pathway involved in almost every individual. For atopic dermatitis, even with our best therapies, not everybody reacts exactly the same way. It makes selecting that right therapy for the right patient a little more complicated. I’d love to get your take, Vivian. Do you have any tricks that help you connect the right patient with the right treatment?

 Often, it’s trial and error…. But the profile of a patient doesn’t stay the same over time. I can give you an example: the flare factor is different. I have patients who previously flared only in the summer, but then environmental factors change. They move around the country, and the weather changes. Then they’ll flare in the winter if they’re in Chicago, for example. Even within 1 individual that changes. That leads to the seasonal or episodic nature of this disease. We don’t get to see that when a patient is on a biologic long term, assuming adherence.

The discussion of a drug holiday comes to up repeatedly in my clinic, but the beauty of oral JAKs is that we can do a drug holiday without the risk of an antidrug-neutralizing antibody. For patients who tend to have more stubborn disease, despite already being on a biologic, we need to know the rules before we break them, and the 3 of us are rule breakers in a way. Adding other oral medications on top of someone who’s already somewhat controlled on a biologic is another option to get stubborn areas, seasonal flares, or stress flares on top of that.

 That highlights real-world clinical practice. We may not necessarily have the disease subset in the way we want it, but now that we have more options, we can mix and match more treatments to get patients under better control.

 Context is so important. When you think about it, we give out prednisone tapers like candy. We do it all the time. If you step back and think about the risks of chronic steroid usage, there’s a long list of things that you don’t want patients experiencing. As Vivian said, wouldn’t JAK inhibitors be great in the short term? They work fast, and you can come on and off them because they’re small molecules. If your frame of reference is steroid tapers and heavier-duty immunosuppressants, they start to look less scary.

The expert panel discusses the heterogeneity of atopic dermatitis manifestation and therapy decisions for individual patients.

Vivian Shi, MD, FAAD

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