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Recent Approval of Oral JAK Inhibitors for Atopic Dermatitis


A brief review of 2 oral JAK inhibitors recently approved for patients with atopic dermatitis.


Christopher G. Bunick, MD, PhD: Dr Lio, we just heard about a topical JAK inhibitor, an atopic dermatitis treatment. But as Dr Cohen mentioned earlier, we have approvals of 2 oral JAK inhibitors. What role are these new oral JAK inhibitors going to play in the atopic dermatitis treatment spectrum?

Peter A. Lio, MD: This is exciting, to finally have powerful new medicines that we can use for appropriate patients. The first thing I’ll say is that the labeling helps us know where these belong. These are for moderate to severe uncontrolled patients who have, in general, failed or aren’t good candidates for other systemic agents. These are put in that zone of second-line systemic agents. That’s appropriate because they’re incredibly powerful. Even though we don’t have that much experience with them because they’re fairly new, what I’ve seen has been pretty exciting.

The downside to these medicines is that they come with some risks. I often say the sword can cut both ways—meaning any powerful weapon can be used against us as well—so we have to be careful. Here those black-box warnings rise to the forefront. I love what Dr [Linda] Stein Gold described about that trial. This makes our job tricky. We understand that there are important class effects of medicines. But we also understand that to get closer to precision medicine, personalized medicine, we’re going to have to figure out both risks and benefits for an individual patient. Clearly, looking at a group of older patients with rheumatoid arthritis—often on other medications and who, by definition, had a cardiovascular risk factor—that might not be the perfect group…to give them a sense of what they can be expecting or what we have to be on the lookout for. That being said, we have to talk about these things in aggregate, and it requires some lab monitoring.

But both of these drugs are exciting, upadacitinib and abrocitinib. In my honest opinion, they seem fairly comparable. What’s neat about them is that they have some more selectivity against JAK1, so that may make them a little more favorable. We don’t fully understand what that means. As opposed to a true pan-JAK inhibitor, these may have a little selectivity that makes them a little better suited for treatment. Upadacitinib was given FDA approval for ages 12 years and up, so it does have that pediatric indication. But abrocitinib is approved only in 18 and older, although my sense is that it may eventually get the same approval because they’ve done some studies in this domain as well. We may see that; it’s a matter of timing. I don’t know, of course.

What I like about both medicines is that they work incredibly quickly. I’d argue that they’re responsible for increasing our level of goal setting for atopic dermatitis disease improvement. They’re both able to show us these incredible scores of EASI-90 [Eczema Area and Severity Index 90] [in patients who are] clear or almost clear. That’s a sea change from what we had before. We understand, at least from some of the head-to-head trials that have already been published, including the Heads Up study—of course, abrocitinib had a similar trial where dupilumab was 1 of the active agents in an arm—is that these are, at the very least, comparable to our biologics but in some settings are superior, especially in terms of timing. All this makes them incredibly useful tools, but we have to make sure we’re on our best game in terms of counseling the patients and picking the patients.

Patient selection is important. We want to ask about risk factors and if they’re comfortable with the amount of risk we’re taking on. Of course, lab monitoring is something we’re going to have to get comfortable with. Sometimes people say, “If they don’t want them to do shots, then they can do this oral medicine.” Maybe, but there are still needles involved because we’re going to be doing a fair amount of lab work. All these things come into play. But already I’ve seen some patients who legitimately have failed everything else we’ve thrown at them and have had incredible response on these medicines. I’m super grateful for them. They’ve already changed some of my patients’ lives, and as a clinician, that’s what we’re in the game for: trying to get people better and able to get back to their lives.

Christopher G. Bunick, MD, PhD: Right on. Absolutely, many dermatologists have probably seen patients with atopic dermatitis who haven’t responded to the prior therapies, so your personal experience is encouraging. I have pediatric patients, so that indication for upadacitinib down to age 12 is useful if they’ve failed injectables or they don’t like needles. They’re very afraid of needles; that’s an important distinction. So having 2 great oral options is a wonderful addition to our treatment spectrum.

Transcript edited for clarity.

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