JAK Inhibitors, Monoclonal Antibodies, Corticosteroids: Choosing a Treatment for Atopic Dermatitis

Two novel treatments for atopic dermatitis, tralokinumab-ldrm and abrocitinib, received FDA approval in the last 6 months. In September 2021, the first topical JAK inhibitor was approved for short-term use in patients with atopic dermatitis. More novel agents are currently being evaluated in clinical trials. 

In this interview with First Report Managed Care, Raj Chovatiya, MD, PhD, director of the Center for Eczema and Itch at Northwestern University, offers insight into how clinical decision making has changed as new therapies become available.

When treating patients with atopic dermatitis, what factors influence a clinician’s decision to use a JAK inhibitor, monoclonal antibody, or corticosteroid?

Atopic dermatitis is a heterogeneous, multidimensional disease. Historically, people have conceptualized atopic dermatitis as itchy patches on the skin in characteristic locations, end of story. But it is more complicated than that.

People can have different types of lesions on different parts of the body with different severity. Obviously, symptoms are important, like itch, skin pain, mental health symptoms, or even sleep disturbances. We know there is variation in the comorbid burden that patients experience. There is also variation in the longitudinal course of the disease and how symptoms present over time.

There are differences between patients in how they have responded to treatments in the past and how atopic dermatitis affects their quality of life. All these things need to be accounted for in one equation when it comes to deciding what is the best treatment choice for a patient.

For atopic dermatitis, we think about treatment as a stepwise additive approach as we transition to different types of severity—people that are clear or almost clear, and then mild, moderate, and severe.

For people that are on the very mild or mild-to-moderate spectrum, we oftentimes think about foundational care, with optimization of bathing and moisturizer trigger avoidance, as well as the use of topical anti-inflammatory agents. This can include topical corticosteroids, topical calcineurin inhibitors, topical PDE-4 inhibitors, and the recently approved topical JAK inhibitor.

For people whose atopic dermatitis is moderate-to-severe, we think about advanced therapies. Many of these therapies are our classic systemic therapies. Phototherapy and oral immunosuppressives are some of these options. Oral JAK inhibitors are also an option, as well as biologic therapies such as monoclonal antibodies.

We think about people in these 2 general buckets: are they topical patients or are they systemic patients? Then, we want to draw out the subtleties of what is important to the patient and the provider. We use shared decision making to balance all these factors and make the right treatment choice.

Topical corticosteroids would be a great option for someone who needs intermittent reactive treatment or even proactive treatment for mild-to-moderate disease. The one nice thing about topical corticosteroids is there are a lot of choices—there is a variety of vehicles and a range of potencies, so this can be a flexible option for a lot of patients.

For people who need a higher degree of control for their atopic dermatitis, this is where we start thinking about biologics or oral JAK inhibitors. The differences between these 2 options really matter in the clinical setting.

Biologic therapies, like dupilumab and tralokinumab, are considered first-line options after somebody has had a nonoptimal response to a topical treatment, like topical corticosteroids. Whereas oral JAK inhibitors are typically going to be the next line option, after somebody has had a systemic therapy of some sort, which can include biologic therapy, an oral immunosuppressive therapy, another oral JAK therapy, or even oral steroids.

Secondly, there are differences in terms of speed of onset. If you need something that is going to act extremely quickly, oral JAK inhibitors are very fast-acting compared to biologics. In the case of efficacy, at some of the higher doses, oral JAK inhibitors can be more efficacious, or at least as efficacious as biologic therapies.

How has clinical practice changed with the approval of new agents?

For so many years, we had limited options for our patients that did not achieve good control of their atopic dermatitis. In many ways, this handcuffed clinicians because, after topicals, we oftentimes had to transition patients to some of the older, broader immunosuppressive therapies like methotrexate, mycophenolate, and cyclosporine.

These agents have data backing them and work, but they are not great long-term solutions. There are a lot of risks that come with long-term use, as well as lab monitoring, so that was always a difficult discussion to have with patients.

Now, with the amount of innovation that has happened in this space—topical, oral, and biologic innovation—we have choices. And I think that is great because atopic dermatitis is such a heterogeneous disease. I keep coming back to this word, heterogeneous. The same thing that works for one patient does not work for another patient. Every patient's disease is different, so people have different values and levels of risk and benefit they are willing to incur.

That is one of the great things about having so many choices: to treat our patients and give them the chance to achieve better short-term and long-term control with targeted treatment that is safe overall.

What unmet needs still exist for this patient population?

One of the areas we talk about often is itch, which is a huge burden for our patients. There has not been incredible innovation in this area, in part because how the nervous system and the skin interact to signal itch has largely been mysterious. So itch is one area in which we are starting to see investment and research. How can we attack this extremely burdensome aspect of the disease that is tied into quality of life and mental health considerations?

Another question that comes up frequently with patients is treatment duration. Atopic dermatitis is a chronic disease, so chronic therapy is an important part of treatment. But patients ask, “What if I treat, and then I stop? Or can I just be off therapy and be under control for a long time?"

We are not necessarily there yet, but this is probably going to be one of the big future avenues we all want to pursue. Many of our patients do not want to be on therapy all the time, so it would be good if the next generation of therapies addresses how we can pursue long-term symptom control, potentially in the absence of therapy, or at lower or infrequent doses.

Thank you, Dr Chovatiya. From your perspective, what should payers keep in mind when evaluating new treatments for atopic dermatitis?

I harped on this before, but there is not a cookie cutter approach to patients with atopic dermatitis. The concept of step therapy, where somebody must try drug A to get to drug B to get to drug C, is antiquated for a disease with so many nuances. And the same stepwise treatment for one patient is definitely not going to apply for another patient. This makes it difficult when clinicians want to start somebody on a therapy, especially knowing we have had so much innovation in this space.

The whole point of innovation was to design targeted, safe therapies for our patients that we can use in different combinations. We have hundreds of therapies in clinical trials right now, and I am hoping that as we get even more choices, our insurers understand a good option for one patient may not be a good option for another.

About Dr Chovatiya

Raj Chovatiya, MD, PhD, is an assistant professor of dermatology and director of the Center for Eczema and Itch at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.