Itch and Treatment Efficacy in Atopic Dermatitis

Shawn Kwatra, MD, is an associate professor of dermatology at the Johns Hopkins University School of Medicine. He also serves as the director for the Johns Hopkins Itch Center and is on the board of directors at Skin of Color Society.

In this interview with The Dermatologist, Dr Kwatra discusses the pathophysiology of and how physicians should manage itch, including the efficacy of current treatments and those in rapid development for atopic dermatitis (AD).

What do you think providers need to know about the pathophysiology of itch in AD?

I want providers to get a sense for what are the key targets of itch and key pathways of itch.  I’d want them to understand the effect various therapies may have on modulating those key players, because oftentimes you need to use a variety of topical, systemic, injectable options. It's important to consider many different factors like if the itch is localized, if it's diffuse, and patient preferences. We just want to expand the toolbox by getting a better understanding of some of the contributing factors to the underlying pathways.

For example, the first agent on market for AD systemic in this new revolution was Dupilumab. Dupilumab targets IL[interleukin]-4 receptor alpha, which we know is a key player in itch pathogenesis. There are also other cytokines like IL-31 which is a new player on the block that actually has rapid efficacy in reducing itch. So talking more about the IL-31 mechanism, folks may not be as familiar with it. There are also other cytokines like IL-13, and a host of JAK [Janus kinase] inhibitors that target multiple cytokines which can help us better understand the relative efficacy and mechanism of action for providers to pick the right therapies for the individual patient that presents to them.

We want to make sure that we are counting for disease in patients that present in every which way. So, ethnicity and race definitely seem to be an important consideration in patients with AD. First of all, there's differences in disease prevalence. There's differences in disease presentation. In particular, African American or Black patients with AD oftentimes present with small bumps, and even prurigo nodules secondarily. This can be in extensor areas as opposed to classical flexural areas.

It's important that we highlight those ethnic and racial differences, and how the disease can present differently because AD is unique from psoriasis in that it can be extremely heterogeneous disease presentation.

What should providers know about current treatments in AD?

There are several studies about how there's differential access to care, therapeutics, and severities. It will be important for industry partners to consider what are present so that therapies that are in development should have balanced populations of patients. In AD this is crucial because the disease can look different, and oftentimes consequently has subtle molecular endotypes.

We know that the T_H2 pathways IL-4, IL-13 and IL-31, and JAK-1 signaling are all very key features of AD. Usually that's often the common feature, but there can be subtle aberrations of different immune pathways. That's why it's important that the therapy be tested in a diverse patient population.

From the lens of therapy, there’s both topical, and oral and biologic injectable therapies which within each class of therapies we can see the different efficacy and mechanism of action. At least even topically, we'll have options from steroids to calcineurin inhibitors, to phosphodiesterase 4 inhibitors, to topical JAK inhibitors, which is amazing. Then systemically, we can go from various oral JAK inhibitors to biologics.

For us clinicians, it's very important to keep pace with all the rapid development. I think that AD is probably the hottest area in dermatology right now and as time has gone by, what we've seen is some of the therapies for psoriasis has started being used for other diseases. Many of these drugs are so important for AD but having a great understanding of these drugs can also help us manage other patient conditions because these are drugs that are being approved and are going to be more available to patients. I think to be a good provider, you're going to have to have a good working understanding of the AD landscape and all of the therapies very well.