Topical JAK Inhibition in Atopic Dermatitis Care Strategies

Transcript:

Lawrence Eichenfield, MD: Peter, if JAK inhibitors are approved, starting with topical ruxolitinib, how do you think it will fit into dermatologic care? How do you think you’ll niche it? But also, how would you compare it in strategy for use with oral JAKs?

Peter Lio, MD: We’ve been chasing topical corticosteroids for more than 60 years. Whenever I compare drugs—which we haven’t had much occasion to do in atopic dermatitis, but we’re about to get a bunch of options—I think of 5 criteria: the efficacy, accessibility, safety, and tolerability. Efficacy is actually 2-fold. It’s how fast it works and the magnitude of effect. That’s why there are 5. It’s called EAST, but E has 2 components. The topical steroids are so hard to beat historically because they’re really efficacious, hyperaccessible, generally very cheap, and they work very quickly.

Their biggest failing is not their tolerability—they’re quite tolerable for most patients but their safety profile in the medium to long term. We’ve been trying to find something that can supplant them. For the first time in my career, the topical JAK inhibitors, like ruxolitinib, have the potential to dethrone steroids or at least be co-kings. They can be right next to them if what we see in the literature bears out. We understand as clinicians that sometimes there are promises that happen in studies that don’t translate perfectly to the real world. There may be issues. Of course, accessibility is very important too, because it’s unlikely that these will be as available, inexpensive, and accessible to patients. We have to see how that all plays out.

But if—there are a few ifs—that’s true, for many patients, these could potentially be a replacement for topical corticosteroids, especially in sensitive areas where we don’t want to use too much, like around the eyes, in very delicate skin, in the flexural areas, or the folds. For my own personal practice, it’s much more likely these will become more important maintenance medicines. We still may use topical corticosteroids to cool the inflammation down, but then across all the severities potentially—mild, moderate, or severe—once we have them better, we could potentially use topical JAK inhibitors to help maintain. They show that they have itch relief and impressive anti-inflammatory potential, but also aren’t a steroidal or systemic agent.

This opens the door to this Holy Grail, if you will, in atopic dermatitis. I just have to be a little skeptical, because we’ve been excited about things before. I’ll believe it once we have it in our patients’ hands and we have some experience. But I’m extremely bullish on them. This has the potential to change our practice and alter the guidelines.

Lawrence Eichenfield, MD: One of the things I like about the development program for topical ruxolitinib is that we talked about the 8-week early study. They did the extension study up to a year, and the design of that was fairly practical, reflecting practice where people would use it twice a day until they got clear or almost clear. And then they’d treat for 3 days beyond that, which is what we tell our patients too, because we know there might be subclinical inflammation. Then they stop, and if there’s recurrence, they could come back and have the extended course over time. It showed it persisted in terms of its impact and the efficacy measures but also without additive adverse effects, with its on-off use over a year, which is so important. I tend to have a fair amount of patients who come under control and look pretty good in the office. But when I ask them about it, they say they’re still itchy at night. Do you think there will be a place for topical JAK for that?

Peter Lio, MD: I definitely do. This might be a great place, because with some of those patients in whom the disease severity and signs of the disease are under good control but are still symptomatic, this is a tough situation. You don’t want to keep wailing on them with topical corticosteroids, because as we’ve heard, we have to be careful of the skin thinning and potential growth issues—especially in littler kids using higher levels of them. This is exactly the role where a nonsteroidal can shine. We have some nonsteroidals that can play this role right now, but the question is whether we can beat them. Can we do something that’s more efficacious and potentially safer that potentially has even better tolerability? We know with some of the existing agents that stinging and burning is a major problem. If this can be better than the vehicle, that would be spectacular.

Leon Kircik, MD: Larry, in the 8-week study, almost 52% of the patients had a 4-point or higher improvement in the NRS [Numerical Rating Scale] itch scale. To your point, it can definitely be a useful agent for itch.

Lawrence Eichenfield, MD: There are lots of secondary data sets, but 1 of the things I like in the adolescent subset is there were like 250 teens in a 12-plus, and we saw a 90% improvement in EASI [Eczema Area and Severity Index]–90. It was pretty high. It was 35% or 40%, which I like. That’s great. I like my topicals to bring them to almost clear.

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Transcript edited for clarity.