Oral Agents for the Treatment of Atopic Dermatitis

EP: 1.A Changing Treatment Landscape in Atopic Dermatitis

EP: 2.The JAK-STAT Pathway and the Mechanisms of JAK Inhibitors

EP: 3.The Benefits of Topical Ruxolitinib

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EP: 4.Oral Agents for the Treatment of Atopic Dermatitis

EP: 5.The Impact of Itch on Patients With Atopic Dermatitis

EP: 6.Safety and JAK Inhibitors

EP: 7.Conversations With Patients Regarding Safety of JAK Inhibitors

EP: 8.The Right Type of Patient for JAK Inhibitors

EP: 9.The Future of Atopic Dermatitis Treatment

Raj Chovatiya, MD, PhD: What’s been your experience with some of the oral agents like upadacitinib and abrocitinib?

Lisa Swanson, MD, FAAD: Both are great. Upadacitinib is approved down to age 12 and abrocitinib, down to age 18, both for moderate to severe atopic dermatitis [AD]. Both are once-daily pills. The biggest take-home message with these oral JAK inhibitors is their speed of onset. That sets it apart. Within hours, within a day or 2, our patients are reporting how much better they feel. A lot of them can’t hardly believe it. A lot of them wonder if they’re experiencing a placebo effect. How could this be true? How could this be working so quickly? Then it keeps working. Patients are super happy, and they express that joy to us. That makes us much more joyful. Thus, speed of action is 1 thing that sets the oral JAKs apart from some of our other therapies.

Raj Chovatiya, MD, PhD: I love it. That’s been my experience too. It’s rare that patients will proactively message me for a good thing. It’s usually something that did not go right or a new problem that’s come up. This has been 1 of the rare circumstances, both with topical ruxolitinib and the oral agents, in which I found that patients had been very proactively saying, “I can’t believe this is working. I’m so happy about it.”

To piggyback on what you said, speed is a nice thing. We haven’t had much flexibility in terms of different routes of administration. An oral therapy is very welcome for people looking for an oral option. But dose flexibility is a nice thing too because unlike some of our biologics—or maybe there’s a general dosing regimen—there are 2 doses for both of these. Upadacitinib is available in 15- and 30-mg doses for atopic dermatitis. Abrocitinib, in 100- and 200-mg doses for atopic dermatitis. The nice thing is that you’re able to see how someone does on a lower dose and increase them if you need to, and then you can get them down to whatever maintenance dose is going to work for them.

This speaks to some of the normal long-term fluctuations we see in disease and the heterogeneous nature of the disease. With those high doses in particular, with a lot of the head-to-head studies that have been done, you can achieve truly deep and meaningful improvements. In many of the signs and symptoms with atopic dermatitis, this is a big march forward. But we’re fighting for a day in which we can talk about, maybe not a cure, but near-complete or total-complete clearance with our therapy.

Lisa Swanson, MD, FAAD: Speaking of that, Raj, I’d like to ask you a question. I’ve found that I haven’t had a patient for whom I needed to advance to the higher dose of abrocitinib or upadacitinib. Has that been your experience? Or have you briefly up-ticked the dose for a little while to get them over a hump? I haven’t had to use the higher doses.

Raj Chovatiya, MD, PhD: It’s a funny question. By and large, I’ve been very happy with the lower dose in both cases. There have been only select instances in which we’ve used the higher dose. As you put it, it’s been transient and not necessarily for long-term therapy, for people who were breaking through or having flares or a particularly refractory disease. You raised another nice point: even though there are multiple doses available, your lower dose does a lot of the heavy lifting, and patients and providers both love less medication.

You mentioned something interesting about speed of onset. That’s something unique about the JAK class in general. I want to make sure the topicals don’t get shortchanged, because topical ruxolitinib has great data to show itch improvement early on in terms of your NRS, or numerical rating scale, scores. You were talking about hours to days, and even in the case of the orals you’re talking about hours to days.

The pharmacokinetics of this response is really cool because even though there are lesions, you might see stuff on the order of days to weeks to several weeks. Itch seems to be extraordinarily rapidly responsive. This probably has a lot to do with the biology of the … vs a lot of what is going on as far as epidermal dysregulation and barrier dysfunction. It’s nice to be able to counsel patients and say, when asked, “What should I be seeing first?” It’s nice to give them a little anticipatory guidance: “You know that itch that’s keeping you up at night and driving you crazy? That’s the first thing you should start to change if you feel things are working.”

Lisa Swanson, MD, FAAD: Before we had all these wonderful systemic therapies to treat bad atopic dermatitis, I thought the itch and look of AD had equal amounts of impact on the patient experiencing it. These therapies have taught me that that’s not the case. The itch is 75%, 80% of what they hate the most about atopic dermatitis. If you make that better, they almost don’t care how their skin looks. They’re just happy they don’t itch anymore. They’re sleeping, and they’re comfortable, and they’re able to focus on work or school or their relationships. You take that itch away, and they’re happy campers.

Transcript edited for clarity