Efficacy and Reported Outcomes With JAK Inhibitors in Atopic Dermatitis


Experts in dermatology discuss efficacy and patient-reported outcomes of topical and systemic JAK inhibitors and dosing guidelines in atopic dermatitis.

Linda Stein Gold, MD: We’ve had a great talk about the topical agent. Peter, you certainly alluded to the fact that we have these oral agents. Can you run us through what have we seen in terms of efficacy and quality of life there?

Peter A. Lio, MD: I think what we’re seeing in general with these new oral medicines is what I like to call the virtuous cycle of drug development. We are learning more about atopic dermatitis and all of its comorbidities and how these run together. We also are adjusting our treatment to its target. I think we’re hearing it today, it is so neat, what we used to settle for even just 5 or 10 years ago, “Hopefully we’ll cool you down for a bit, get you a little better.” Now we’re saying, “I want you clear, and then I want you clear safely going forward,” and ideally, we want people to be able to keep this up indefinitely. I think they are allowing us to access that for these patients. As you might expect, we are seeing a very rapid improvement in all the symptoms and signs of atopic dermatitis for our oral JAK inhibitors. We are seeing incredibly deep efficacy of these drugs, and of course both of these drugs we have in the United States have 2 dosing levels. There’s sort of a starting dose, and then each one has a double dose that can be used, particularly if a few months in you’re not seeing what you would expect.

Then we are seeing all of those comorbidities we talked about, we are seeing them improve as well, so we are seeing the depression, the anxiety, all these other markers. I would say at some point we don’t even have to keep measuring all these things because we know they should be strongly correlated. In fact, it would be noteworthy or newsworthy if we suddenly saw a disparate finding where the skin looked better, but the patient didn’t feel better. Fortunately, they do run together, so all of these things are improving. I think the next big question for us that our patients are asking all the time is: “How long do we use these, and how do we come off of them?” This is a wonderful problem to have. We’re actually at the point now where we have people better safely and we can ask that next question.

Linda Stein Gold, MD: That brings up an interesting issue. We do have the 2 doses. For both of the systemic JAKs, it is recommended to start with the lower dose initially. Are you comfortable if a patient is not where they need to be, accelerating to that higher dose?

Peter A. Lio, MD: I definitely am. I am happy to say that in my practice, it is very rare. I only have a handful of people who have needed that higher dose. With abrocitinib, there’s specific guidance on the label saying at 12 weeks is the time. With upadacitinib, there’s no guidance, so you could do it after a month or two, but I think that’s a reasonable time, giving it a month or two and seeing. In general, I haven’t needed it much. If we do, I still feel pretty good about it because we know, in particular for upadacitinib, for other indications there are even higher doses beyond what we use, 45 mg in ulcerative colitis. We know this range is probably still reasonably safe, but I do intensify my laboratory monitoring especially when we increase a dose. I’ll check again a month later just to be absolutely certain we are OK.

Linda Stein Gold, MD: If you are using an oral JAK inhibitor and a patient is exactly where you want them to be, are you comfortable adding a topical with that?

Peter A. Lio, MD: Very much so. I would say essentially 100% of my patients are using a concomitant topical therapy. I think it is really good, but what I am looking for is them to be needing it less and less. I like to say, “I’m going to see you back, and I’d like you to track for me how much you are using your medicines.” This way we can look, especially if they are using a topical steroid, but even for my patients who are sensitive to the 8-week mark with a topical JAK inhibitor, I want to know. Then I can say, “You’re doing great. The last time I saw you, you were using it 2 or 3 weeks out of the month, which is maybe on the high side of using your strong medicine. Now, you only used it a week in aggregate. You are doing so much better.” Of course, we’re going to pair that with our ADCT [Atopic Dermatitis Control Tool] to get an overall sense, and this is how we know we’re going in the right direction.

Transcript edited for clarity

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