Comprehensive Insight into Atopic Dermatitis: Understanding Disease Burden, Treatment Strategies and Emerging Therapies | Written Recap

Matthew Zirwas, M.D., a nationally known expert in atopic and other kinds of dermatitis, is a dermatologist at DOCS Dermatology in Bexley, Ohio, outside of Columbus. In this Managed Healthcare Executive K-Cast video series, Zirwas discussed how atopic dermatitis presents differently in children than in adults, its symptoms and effects on social life and sleep, treatment choices, barriers to access and unmet needs.

How it presents

Atopic dermatitis in children typically presents before children are 5 years old, and sometimes in children as young as 6 months, Zirwas said. In pretoddlers, it occurs on the cheeks and on the elbows from crawling, he said. But once children are toddlers and older, the affected areas are the neck, the folds of the arm and behind the knees, according to Zirwas. Children with atopic dermatitis also develop atopic comorbidities, including food allergies and asthma.

Adults with atopic dermatitis present differently. For adults, the skin on the proximal arms and legs (the area nearest the trunk) and the trunk is typically affected, and it is not associated with atopic comorbidities, Zirwas said. “Some of the data now suggest that we’re not very good at identifying adult atopic dermatitis in adults, because it looks so different [than it does in children], and it’s not associated with atopic comorbidities,” commented Zirwas.

The diagnostic criteria, commonly referred to as Hanifin and Rajka [named for its co-authors, Jon Hanifin and Georg Rajka], came out in 1980 and are very sensitive and specific for children, Zirwas said. The 2014 diagnostic criteria issued by the American Academy of Dermatology are more accurate for adults, he said.

Social, health and financial effects

The rash associated with atopic dermatitis can affect people’s social lives, Zirwas said. “If you’ve got a bad rash on your hands, imagine every time you shake hands with somebody, they are thinking, ‘Oh my God, did I just catch something from you?’ Or if you’ve got a rash on your face as well. So, there are those visible aspects that are very socially and professionally impactful, whether we’re talking about a kid in school or somebody at their job,” he said. Affected areas usually covered by clothing can also affect interpersonal relationships, he said.

The itch, though, is the “really important part of the disease,” Zirwas said. Everyone has experienced itch from poison ivy, a mosquito bite or some other cause, he said. “Well, imagine that you had poison ivy every single day of your life, over a wide area of your body. That’s what it’s like to live with atopic dermatitis,” Zirwas said. The itch interferes with sleep, and the related sleep deficits have been linked to neurodevelopmental issues among children and to daytime drowsiness, mood and decreased work performance
among adults, he said.

Zirwas also described a “hidden burden” of atopic dermatitis, particularly on the parents of children, with some data showing that they spend approximately 20 hours a week dealing with their children’s atopic dermatitis. Zirwas explained that atopic dermatitis is directly driven by environmental factors, such as the clothing, bathing, humidity and air quality that parents try to manage. For adults, it is a similar story, he said, although probably not quite as time-consuming, Zirwas said. The annual out-of-pocket costs for moisturizers, bathing products, clothing and other steps to mitigate environmental factors can add up to approximately $2,000 annually, a figure that does not include
medication costs, he said,

Topical treatments

Topical steroids have the longest track record as a treatment for atopic dermatitis, Zirwas said, and they help with the redness and the itching caused by atopic dermatitis. But atopic dermatitis degrades the barrier function of the skin, according to Zirwas, and topical steroids make that worse. That is why, he said, topical steroids rarely make the condition go into remission, and it rapidly relapses when patients are using them.

The calcineurin inhibitors Protopic (tacrolimus) and Elidel (pimecrolimus) were the next topical treatments to become available, Zirwas said. He described them as “reasonably inexpensive, but not very effective,” with a slow onset of action. In addition, many people experience a burning sensation.

Eucrisa (crisaborole), a PDE4 enzyme inhibitor, was introduced next. Zirwas said it also has a slow-onset action and is not very effective — “not a particularly good drug,” he said.

Zirwas said there are now three new drugs for atopic dermatitis. Opzelura (ruxolitinib) is “by far the most effective topical therapy we’ve ever had for atopic dermatitis,” he said. It works “incredibly rapidly” and helps with the itch in about 15 minutes. Zirwas also said it is “incredibly effective” and that for “75% to 80% of people, their disease is completely controlled long term with as-needed use.”

Opzelura is a Janus kinase (JAK) inhibitor, Zirwas noted, and comes with a boxed warning talking about “scary things,” such as a suppressed immune system and increased risk for heart attack, stroke, blood clots, cancer and death. “We don’t think that any of those are real risks with using a JAK inhibitor topically, but the warnings are still there. That makes some patients very hesitant to use it, especially parents of young children,” he said.

Zirwas mentioned two other topical treatments, Vtama (tapinarof) and Zoryve (roflumilast). He described them as effective drugs with very good safety profiles, but not as effective as Opzelura. Zirwas noted that they do not come with the boxed warning that Opzelura has.

Opzelura, Vtama and Zoryve have been game changers, Zirwas said. “They have taken atopic dermatitis from something that was very difficult to manage to something that now is pretty easy to manage, assuming we’re able to access the treatments for our patients, because they are relatively expensive,” he said.

Patient preferences and treatment plans

One of the main decisions in atopic dermatitis is whether the disease can be treated with a topical cream or needs systemic therapy, such as Dupixent (dupilumab), Zirwas said. If the atopic dermatitis is affecting a large part of the body’s surface area, a topical treatment may not be feasible, he noted. If 50% of an adult’s body surface area were affected by atopic dermatitis, as many as five to 10 tubes of topical treatment might be needed. Zirwas noted that topical treatment is much easier in children because their bodies are smaller, and parents typically apply the cream.

Zirwas said that the topical treatments “in the modern era” are so effective that they can be used intermittently. “Because the drug works so well, that tube often will last for months, rather than having to be refilled on a monthly basis,” he said.

Patient preferences factor into treatment choice, Zirwas said: Does the patient want the most effective treatment or the one with the fewest safety warnings? If topical steroids are used, they are used as a first-line therapy, Zirwas said. If a patient uses them for a few days or a week and their disease goes away, that is a positive outcome. But he stressed that they are not a good long-term option.

If a patient has too much body surface involvement or topical treatments do not work, then the next patient preference to consider is oral administration or injection. If the patient prefers injection, then one of the issues to consider is whether the patient has atopic comorbidities, such as asthma or eosinophilic esophagitis. If they do, Dupixent will treat all those conditions. If the patient does not have atopic comorbidities, then the choices are Adbry (tralokinumab), Ebglyss (lebrikizumab) and Nemluvio (nemolizumab). Those three drugs have a better safety profile than Dupixent, according to Zirwas, but have the drawback of not treating the atopic comorbidities.

Zirwas said he considers Adbry and Ebglyss very similar drugs and noted that Nemluvio has a different mechanism of action. He described Adbry and Ebglyss as extremely effective for the rash caused by atopic dermatitis and very effective against the itch, whereas Nemluvio is extremely effective against the itch and very effective against the rash.

“So, then it’s asking the patient, what’s a bigger issue, the itching or the appearance of your disease? And that helps us in making that final determination [about treatment] and in shared decision-making,” Zirwas said.

Barriers to access

The topical steroids are very easy to access because they are cheap, Zirwas said. The topical calcineurin inhibitors and the original PDE4 inhibitor, Eucrisa, are not very effective drugs, he said. “The only time we ever use them, or that they really make a lot of sense, is when other better topicals are simply not available without a step through. But I will tell you, 100%, if my kid had atopic dermatitis, or if I had it, or if any of you, or any of your kids, had it, you would not want any of those drugs. They just don’t work very well,” Zirwas said.

On the other hand, Zirwas said that low-cost alternatives ought to be tried. “The healthcare pie is limited,” he said. Dermatologists will typically prescribe a topical steroid to control the symptoms quickly and then have them transition to a topical calcineurin inhibitor. If that approach works, “great, we’ve been able to treat that patient at a very low cost and gotten them a good result,” he said. If it doesn’t work, then the hope is that step edit criteria set by insurers have been satisfied, and the patient can move on to more advanced therapy.

Opzelura, Vtama and Zoryve are “incredibly effective drugs,” Zirwas said, that can be used anywhere on the body.

“We really are just telling patients, ‘Put this on anytime you’ve got eczema, anywhere you’ve got eczema. Once your eczema clears up, stop using it until it comes back,’ ” Zirwas said. “These are the first drugs that that kind of instruction really works on, and it’s part of why these drugs are really life-changing for patients, because they now feel confident that if their eczema flares up, they’re going to be able to go home and use their topical and it’s going to work quickly and get that flare-up under control.”

Dupixent was a ‘game changer’

The newer topical agents have transformed the care of atopic dermatitis that is mild and affects a relatively small area of the body, Zirwas said. The systemic therapies have dramatically changed the approach to patients with more severe cases that affect a larger proportion of the body, he said. “Dupixent was obviously the biggest change, because until then, we had literally no effective therapies for widespread or moderate to severe atopic dermatitis,” he said.

Dupixent is a very effective drug, he said, and real-world studies show it is adequately effective, meaning that it works well enough in 90% of people. Zirwas said there are alternatives to Dupixent, and that having choices was important, but none of the other drugs have displaced Dupixent. “I would say there hasn’t been another drug that has been, ‘Wow, this is way better than Dupixent.’ It’s really been, ‘Well, this drug is better in this niche situation or that niche situation, or this is good whenever Dupixent doesn’t
work well enough.’ ”

Cost-effectiveness

Older systemic therapies, such as methotrexate, had toxicity issues and were not very effective at the doses that were not toxic, Zirwas explained. In contrast, the new drugs are “incredibly effective, incredibly safe,” he said, but have a high price: “shockingly better drugs also shockingly more expensive.” The cost-effectiveness trade-off is a “cheap drug that didn’t work or an uber-expensive drug that works unbelievably well.” Zirwas again stressed how much better the drugs are than those of the prior generations.

“If I was a patient or had a family member who had atopic dermatitis, I would do almost anything to get on one of the advanced systemic therapies as compared to the traditional systemic agents,” he said.

Monitoring

Zirwas said the “biggest thing” about incorporating the newer, more effective topical treatments into clinical practice is striking the right balance in monitoring and adherence. Data show that the more frequently patients come into the office, the more adherent they are, he noted. But in his experience, the new topical treatments are so effective that Zirwas said he is mindful of having patients come in too often. “We don’t want to do excessive monitoring and drive up costs that way, but we don’t want to undermonitor,” he said. Zirwas said three months does seem to be a “sweet spot” for checking on whether patients’ atopic dermatitis is getting better. If it isn’t, then the prescribed drug is probably not the right drug, and he considers switching to a different one. But if they’re getting a lot better, “we probably want to give them six to eight months for the drug to reach its full effect,” he said.

Unmet need

In Zirwas’ view, the biggest gap in atopic dermatitis treatment is therapy for widespread disease — a large percentage of the body surface area is affected — but the disease is mild: “It’s a little bit pink, it’s a little bit flaky, it’s itchy, but it’s not driving them
insane.” The widespread disease makes topical treatment impractical, but systemic therapies aren’t warranted if the disease is mild, he said. Drugs are in development to meet this need, said Zirwas, and he mentioned phase 2 trials of a reactive aldehyde species inhibitor.

Managed care

Zirwas said the difference between the treatments before 2017 and those that have been introduced since is stark. “As physicians, we’re taking these people who are absolutely miserable, having their lives ruined; they’re constantly in misery. I frequently [would] hear from people, ‘I just can’t go on like this. I can’t go on like this,’ and being able to get them on...these highly effective therapies has really just been indescribable.”

But Zirwas said it can be difficult to get patients on the newer, effective drugs — and keep them on them — because of the cost. He said he understands the challenge that poses to his “managed care colleagues, but I really want you to understand that the price of the drugs is worth it for how incredibly dramatic the step up in efficacy was from the traditional agents.”