Advancements in Treating Atopic Dermatitis

By Amy Paller, MD, as told to Stephanie Watson

Atopic dermatitis treatments have come a long way.

In the past, we had to use immune-suppressing drugs in people with moderate to severe disease. Many doctors, especially those without expertise in skin care, have used oral steroids. But we can’t keep people on these drugs long-term. Steroids cause serious side effects like weight gain and high blood sugar. They also have a rebound effect: The atopic dermatitis comes back pretty quickly, and with a vengeance.

Other immune-weakening drugs like cyclosporine, methotrexate, mycophenolate, or azathioprine have been the favorite of dermatologists. But these are also strong medications that need frequent blood tests to watch for side effects.

We needed a new treatment approach. Atopic dermatitis is a serious problem. The itch can be so severe that it keeps people up all night scratching. Severe flares can affect your ability to go to school or work and to have a social life.

It’s exciting to live in an age where we can create medications to target the pathways underlying diseases. That’s being done right now with atopic dermatitis.

Finding the Cause

From studies, we found that people with atopic dermatitis have an immune system imbalance. Their bodies make too much of certain things that inflame their skin when they’re exposed to irritants, bacteria, or allergic triggers like pollen and pet dander.

We know that the skin barrier is flawed in atopic dermatitis, which makes our skin-based immune system react more than usual when triggered on the surface. In addition, many people with atopic dermatitis do not have enough of an immune response against bacteria on their skin. All of these factors work together to trigger atopic dermatitis flares.

By understanding the driving forces behind the disease, we’ve been able to develop treatments that target the out-of-control immune system. Now, we can manage atopic dermatitis much better.

New Treatments

The FDA has approved two new treatments for atopic dermatitis in recent years. Crisaborole (Eucrisa) is the first phosphodiesterase-4 (PDE4) inhibitor. It’s a cream that blocks the enzyme PDE4 to reduce inflammation.

Dupilumab (Dupixent) is a biologic drug. It blocks the effects of proteins called cytokines that the immune system makes: interleukin-4 (IL-4) and interleukin-13 (IL-13). These contribute to the inflammation, reduced skin barrier, and severe itch of atopic dermatitis. Blocking them reduces the inflammation and the itch.

This drug has transformed atopic dermatitis treatment. Though it doesn’t work for everybody, in those it does help, it is life-changing. Sometimes, it starts to work in the first weeks after starting it.

The other advantage of dupilumab is its safety, especially in children. Immune-suppressing drugs like cyclosporine come with long-term risks like kidney damage and high blood pressure. That’s why we have to do regular blood tests in people who take these drugs.

With dupilumab, we don’t need to do blood tests. The only side effects are reactions where the needle goes in and possibly inflammation in the eye, which an eye doctor can treat. So now we can feel more comfortable treating patients safely.

Dupilumab has really been a game-changer. My patients tell me how it has changed their lives. Some of them hardly have to use the thick creams anymore to control the itch. They can play sports and go to parties again.

Coming Soon

Dupilumab is just the tip of the iceberg. Two more biologics should be coming out in the next year or so. Like dupilumab, they also target the effects of IL-13, and they have a similar safety profile. That means we’ll have more safe choices to prescribe for our patients.

The other group of medications for moderate to severe atopic dermatitis that’s coming out is the Janus kinase (JAK) inhibitors. These drugs block the messages that signal the immune system to make more cytokines.

Three JAK inhibitors are in development, and they look promising. One of them, abrocitinib, worked better than dupilumab in a head-to-head study.

Unlike injected drugs like dupilumab, JAK inhibitors come as a pill that you take daily. That is a huge plus for people who don’t want to get shots.

The big question is safety. Two JAK inhibitors that are used to treat rheumatoid arthritis and are in development for atopic dermatitis have a black box warning on the label about serious risks like cancer, blood clots, and infections.

None of these risks has come up in the studies on atopic dermatitis. But JAK inhibitors can cause nausea, headaches, acne, and higher odds of herpes infections, with risks depending on the drug. Also, people who take them will need blood testing to watch for problems.

New Topicals

A few new topical drugs — meaning you put them directly on your skin — are in development, including a topical version of a JAK inhibitor. We’re excited about these drugs because they’ll offer an alternative to topical steroids.

Another PDE4 inhibitor is also in the works, and it may be more potent than crisaborole.

Tapinarof is the first in a new class of topical drugs called a therapeutic aryl hydrocarbon receptor modulating agent (TAMA). It works in a different way to reduce the inflammation and itch of atopic dermatitis.

One problem for many people who use nonsteroid topical drugs that are currently on the market for atopic dermatitis (topical calcineurin inhibitors like tacrolimus and pimecrolimus; crisaborole) is burning or stinging. All of these new nonsteroid drugs seem to be less likely to cause these problems than ones we have now.

Another new treatment is a skin spray with healthy bacteria. These good germs fight off the bad bacteria that make atopic dermatitis worse and cause infection.

A few of these sprays are in development, and I think they will be very interesting to watch. They may be able to reduce inflammation and improve atopic dermatitis. Plus, I think a lot of people will like the fact that they’re natural — replenishing the “good bacteria” on the skin.