Dr Raj Chovatiya on Optimizing Patient-Centered Care in Atopic Dermatitis

By better understanding the nature of atopic dermatitis and its varying comorbidities, providers might be able to better predict patient outcomes, said Raj Chovatiya, MD, PhD, assistant professor of dermatology, Northwestern University Feinberg School of Medicine.

For a long time, there was a notion that atopic dermatitis was really a disease that affected children and manifestations in adulthood were not a big deal, which can be a challenge for diagnosis and treatment for these patients, he said.

In an interview with The American Journal of Managed Care^® (AJMC^®), Chovatiya provided a thorough overview of the current treatments available and in the pipeline for atopic dermatitis. With evolving research and the promise of new therapeutics, he thinks providers will better be able to understand how to treat intermittent disease versus continuous disease and compare the outcomes.

AJMC: Can you describe a typical patient journey for atopic dermatitis?

Chovatiya: I think that probably depends a little bit on age. For younger individuals with atopic dermatitis, particularly the pediatric range, oftentimes the first place that they're going is their general pediatrician. They are the ones that are oftentimes managing a lot of cases of mild or moderate eczema. Pediatricians perhaps are even better versed in atopic dermatitis management than their adult primary care counterparts just because of how frequently they see it. Atopic dermatitis itself is a prevalent disease overall, but even more prevalent in the pediatric population than the adult population.

Oftentimes, when the case becomes more in the moderate to severe in range, or one that's not necessarily responding to topical therapy, that's the point at which they might see a pediatric dermatologist or even a pediatric allergy immunologist. Pediatric allergists also manage atopic dermatitis, as well. There's just not that many pediatric dermatologists, so sometimes that referral and getting an appointment to see one can be quite difficult outside of sort of many major academic medical centers.

In the adult range, it's a little more heterogeneous in the sense that for a long time there was this notion that atopic dermatitis was largely a disease of childhood, people grew out of it, it wasn't really a thing in adulthood. Or, for people that did have eczema, it was just a little eczema and not a big deal. We still fight that old notion of disease when we are trying to talk about the true burden that atopic dermatitis places, particularly in adults. So, a number of adults may initially start with primary care. Many of them may also go directly to dermatology. Some may end up going to an allergist. Then, there are others who possibly may not even seek care, because they've been kind of told there's either nothing to do, or it's not that big of a deal. That is definitely the population that needs the most activation in terms of having them understand it’s a real disease, with a huge burden, and there are a lot of things that we can possibly do.

So, for the route of a patient seeing a primary care physician initially, they might get management with emollients and maybe very mild topical corticosteroids. But by and large, most patients that require higher potency topical corticosteroids and systemic therapies are going to be seeing a dermatologist for ongoing care.

AJMC: Diagnosis is a concern as well, how do you ensure timely diagnosis in atopic dermatitis?

Chovatiya: We want to actually get people into care and then actually have people that understand how to make the diagnosis itself. I feel that there's probably better diagnosticians in the pediatric range, because pediatricians are sort of looking out for it. In the United States, for example, the prevalence of atopic dermatitis is almost like 13% in the pediatric population. It’s something very common and something that we are often looking for. In adults, it's mixed because oftentimes, many adult health care providers are not necessarily thinking about eczema or atopic dermatitis, because it's largely thought of by many to be a childhood disease.

The thing that really is important for timely diagnosis is being connected to health care, patients being open about their symptoms, and patients not underplaying what they go through day-to-day in terms of their skin symptoms and other aspects of the burden, as well. You can imagine that delayed diagnosis can result in a higher severity of disease, one that maybe becomes more refractory to topical therapy and requires systemic management, or even at the point where it's quite severe that it's related to other comorbidities that are connected to the disease: higher burden of itch, skin pain, mental health, sleep disturbances, and things like that.

Oftentimes, people that have the most severe disease are the ones that end up having higher rates of health care utilization. They're using the emergency room more, urgent care more, and they have much more acute episodic care as opposed to good long-term ongoing care.

AJMC: What is the utility of the 1980 Hanifin and Rajka criteria in clinical practice?

Chovatiya: Most existing formal diagnostic criteria are heavily grounded in the Hanifin and Rajka criteria, originally proposed by Jon Hanifin, MD, and Georg Rajka, MD, back in 1980. The way that these criteria work is there are a series of major and minor points that you have to hit. For the sake of brevity: on the major front, you're looking for 3 or 4 major features: pruritus, typical morphology and distribution—that refers to flexural lichenification results and facial or extensional eruptions in infants and children—chronic or relapsing dermatitis, and a personal or family history of activity. Then we need to get 3 minor points of a much longer list of about a couple dozen features that are oftentimes associated with the disease.

Now, as you can imagine, this is probably a little clunkier in day-to-day clinical practice. I feel like by and large, it's not necessarily used in routine clinical settings even though this is oftentimes what's used in many clinical trials or other larger studies as the gold standard.

There are other criteria, that have tried to make this a little simpler and approachable. To give you a good example, the American Academy of Dermatology's guidelines really attempt to encompass the full age range and broaden the definition. Essentially, you're looking for some type of eczema or dermatitis and you're looking for pruritus and that’s basically it, and a lot of that's based on expert opinion. There are certain sub features, as well, but that's kind of the big thing that you're wanting to hit.

There are other criteria around the world that have really tried to take different approaches to it. There is another criteria called the United Kingdom Working Party Criteria where you're trying to hit a few major criteria on a smaller list. In general, they're all based on the same Hanifin and Rajka criteria.

AJMC: How do clinicians and payers best evaluate evidence from clinical trials when assessing new therapies?

Chovatiya: I think that in trials even a lot of the measures that are used are not necessarily ones that are made for routine clinical factors. In atopic dermatitis, 2 of the most common measures are the EASI, or Eczema Area and Severity Index, and then the SCORAD, or SCORing Atopic Dermatitis. Two composite criteria that take into account lesional severity, location of lesions, and overall extent in terms of body surface area. Those take a little while to compute and you have to be very adept at using those to actually get them scored pretty quickly. Those aren't used so much in practice. People tend to use more of a composite…maybe it's much closer to an investigator’s or physician's global assessment of the severity at that standpoint.

So, by that same logic, while the Hanifin and Rajka Criteria perhaps are not necessarily whipped out every time someone is trying to make that diagnosis, I believe largely the main principles are there, and that would be what the American Academy of Dermatology went for in their last round—those more general principles. I don't think that this is too much of a question, when it comes to talking to health care providers about their feelings based on studies. If anything, it gives you a little more confidence that the studies were done in a very clean, systematic way.

AJMC: Recently you proposed a novel classification framework for atopic dermatitis the DESCRIBE-AD. What are the goals for this tool? How does it work?

Chovatiya: This is just one example of many different ways we can perhaps try to visualize the multidimensional nature of disease. When I say multidimensional, atopic dermatitis is more than just scaly patches on the skin. There are many different ways that lesions can look. They can present in different locations. They can have a variety of extent in terms of body surface area. Symptoms can vary beyond just itch and skin pain, mental health, and sleep. There are a variety of comorbidities. The longitudinal course of disease can look very different. The quality-of-life burden could be very different from person to person. Even the response to treatment and potentially positive or negative events related to treatment itself.

It is really hard sometimes to talk that whole language from patient to patient and compare across different subsets. The goal with that particular study was trying to suggest that there are a lot of things to think about when it comes to atopic dermatitis. It might be helpful if we're all talking the same language, and maybe being systematic about how we think about all of these aspects of disease. Perhaps that's going to be the way in which we can better unlock different therapeutic subsets. If we understand who is hitting what boxes we might be able to, hopefully, one day predict what might be the best treatment for the best patient.

AJMC: Can you talk us through the current treatment landscape for atopic dermatitis?

Chovatiya: It’s one of the most exciting areas in dermatology just given how much is happening, and how much interest there is in clinical trials and how many potential treatments are in the pipeline, and how many new approvals we've had. Generally speaking, when it comes to atopic dermatitis, we think about stepwise additive treatment, usually starting with milder disease where we're just doing lifestyle modifications in terms of optimization and moisturization, optimization of bathing, and then removal of any type of known triggers of itch or eczema.

Moving upwards, we then think about our topical anti-inflammatory therapies for mild and moderate disease, which includes topical corticosteroids, topical calcineurin inhibitors like tacrolimus and pimecrolimus, topical PDE-4 inhibitors like crisaborole, and the most recently approved new therapy in this category, topical ruxolitinib cream, which is a topical Janus kinase (JAK) inhibitor. With the sort of moderate-to-severe group is when we start thinking a little bit less about topical therapies, and we start thinking a little bit more about systemic therapies. This is where we think about injectable, oral, and phototherapy, as well.

Phototherapy, typically narrowband ultraviolet B–based therapy, is something that's definitely an option for patients. As far as oral therapies go, there are your classic oral immunosuppressants: this should be things like methotrexate, ciclosporin, mycophenolate, azathioprine, things that can work broadly, but they do suppress the immune system and, unfortunately, they can suppress immune activity and result in a variety of other systemic side effects that require lab monitoring.

Newer entrants into the oral space include the oral JAK inhibitors which are sort of very potent, exciting targeted therapies that work in a more specific fashion than previous oral therapies. These JAK inhibitors include upadacitinib and abrocitinib as well, both of which can definitely result in very deep responses and improvement both in the signs and symptoms of atopic dermatitis. So, that's one exciting advancement this past year.

Then we have the biologic therapies. Dupilumab was the first one of this entrant, the monoclonal antibody that binds to the shared IL-4 receptor α-subunit that's used by IL-4 and IL-13 for signaling in atopic dermatitis. Those are 2 really important signals that hit highly upstream when it comes to disease pathogenesis. We had another entrant into the biologic space about a year ago, and that was tralokinumab, which is a specific anti–IL-13 antibody which targets one of those signals that's important.

AJMC: How might the management of atopic dermatitis differ for patients with relapsing remitting disease versus those with chronic persistent disease?

Chovatiya: The big question there is that does somebody require year-round consistent treatment if their disease is a little more intermittent, or can someone effectively start and stop their interventions? There isn’t a great answer to that, but I think we're going to end up learning a lot more about this because with biologic therapies, typically the way they work is they have a little bit of a slower onset. It takes them a lot to get therapeutic, and you're typically not using them at the signs and symptoms of atopic dermatitis right when they break out, but rather consistently. Whereas, with oral therapy, while they definitely can work consistently in the long run, that does allow you to understand a little better about how episodic management might work in terms of a safe targeted therapy.

I think that over the next few years as we get more and more entrance into this space—particularly targeted topicals, targeted orals, and then targeted biologics—we're going to understand exactly how you can treat intermittent disease versus more continuous disease, and whether or not there's an actual difference in overall outcome.

AJMC: What are some of the biggest unmet needs of patients with atopic dermatitis?

Chovatiya: Obviously even with the therapies that we have now, there are still a huge number of patients with moderate to severe disease that require management. A lot of that just has to do with reaching those patients, getting them into the clinic, getting them to have a discussion about therapy, and really moving forward both the health care provider dialogue and patient understanding of what's out there for atopic dermatitis.

A subset we oftentimes do tend to sort of forget about, because we think of more severe diseases, are mild-to-moderate groups. They encompass the biggest chunk of patients with atopic dermatitis. They can have consistent symptoms and signs of disease, but I think we understand a little bit less about what that means overall in terms of their chronic burden, because the moderate-to-severe population is the one that gets studied a lot for these newer therapies. I think that, hopefully, over the next decade or so, we're going to understand a bit more about the people that have more chronic persistent but milder disease.

In terms of the symptoms associated with disease, itch has always been a difficult thing to treat and treating the disease with many therapies can help with itch, but there are still patients that do have persistent high levels of itch. A lot of the comorbidity that we associate with disease as well. So, both atopic and allergic comorbidities and non-atopic comorbidities. Are these things that are going to improve as we improve disease? Are they disconnected? Are there ways we could hit multiple targets at once? I think that's going to be another area that we learn a lot more about. Finally, how do we connect the right patient to the right treatment? Now that we actually have a lot of choices and we're going to add even more, hopefully we'll begin to understand how we can actually individualize treatment.

AJMC: What is the economic burden of atopic dermatitis?

Chovatiya: We're talking about a disease state that when you combine direct and indirect costs in the billions of dollars in the United States. Direct costs are the obvious thing we think about with disease when it comes to real health care utilization, when it comes to outpatient visits, medications, and emergency/urgent care. It is that indirect cost aspect that actually is a huge one when it comes to missed work, lost productivity, and other aspects related to quality of life where they're sometimes really difficult to measure. I think that this is a big one for atopic dermatitis and one that we probably need to understand a little better, but probably is a sizable chunk of disease.

People that have chronic disease burden are oftentimes just not at their highest capacities as an individual, and they’re really not as productive as they could be in all the things they do in life. I think that's more of the silent burden that we often think about with disease.

The obvious one is still very clear. Study after study has shown that patients with atopic dermatitis spend a lot when it comes to prescription medications, out-of-pocket costs for therapies, and on their normal outpatient health care utilization. Patients with atopic dermatitis have increased visits to the emergency department, increased visits to urgent care, oftentimes increased hospitalization, and longer and more expensive hospitalizations, as well.