Evolution of Treatment Selection for Pediatric Atopic Dermatitis Management

Raj Chovatiya, MD, PhD: That was a tour de force master class on how to dose. Peter, I don’t know how you and I could follow this. I’m just going to call you if I have dosing questions. I might toss a different question over to Peter, so we don’t embarrass ourselves because that was so good. Maybe you can tell me, Peter, what do you think about long-term treatment and therapy, and what you used to do vs what you do now with dupilumab? How is this going to change in terms of chronic treatment for people with pretty chronic moderate to severe disease?

Peter A. Lio, MD: This is my hot take on this area. I think that the next frontier, obviously we want to cure people. That’s the goal. We’re ways away from that I think, I don’t think we fully understand enough to be able to just turn it off. But the next frontier is remission. So all of my energy right now is focused on, can we induce remission for patients and what treatments are better at doing this? I wrote paper a couple years ago saying that dupilumab I really think can induce remission in some patients. Here’s the idea. We talked about this vicious cycle with those 5 pillars all fueling each other, no matter where you start, you’re getting barrier damage, inflammation, nerve-ending changes, microbiome dysbiosis, and of course, neurobehavioral issues. If you get things under control, then the barrier gets stronger. The microbiome normalizes, the inflammation calms down, the nerve endings morphologically and physiologically go back to normal, and the behavioral cycles go back to normal. Thus that vicious cycle goes to a virtuous cycle, and it follows that we should be able to pull back.

Now, not everybody, I wish everybody, but in some patients I’ve been able to successfully stop dupilumab and follow them for many weeks and even months after. We know it’s in your system for maybe 8 to 10 weeks. So this is long past when there’s any trace of the drug in the system. In this report we did, not a single patient had a rebound, so that’s part 1. We know with prednisone or prednisolone, we expect at least some of those patients to have a big rebound spike, worse than their baseline. Not a single patient in our cohort got back to their baseline, even over all those months after. I call this a relative remission, and I think that is my next frontier.

What I’m doing now is I tell patients when they say, “Is this forever? Is this like a blood pressure medicine or diabetes medicine?” I say, “No, not necessarily. I’m not going to make a false promise and say definitely no, but not necessarily. Our goal is to get you better for a period of time.” I usually define that as 6 months to a year. If they’re doing great for that longer period, and I really feel like things are back to normal, I think it is reasonable to start discussing either pulling back or spacing people out. We know some of the newer medicines, in fact there is a newer biologic that only has an indication for adults. It has a secondary dosing regimen that spaces it out to once monthly if they’re doing well. I think we can take lessons from that and use it for our other medicines, or even stopping completely and going back to other things we did leading up to it. So going back to topicals or maybe going back to phototherapy, things like that. I do believe that for at least a substantial portion of patients, we’re going to be able to get them in that remission state.

Raj Chovatiya, MD, PhD: A hot take indeed. But I think that we all agree that remission is something we all think about, of where can we get people to the point where we don’t have to burden their lives so much in terms of the treatment they use. You highlighted a very interesting point. They did this, even though it hasn’t been highlighted, in the case of dupilumab compared to tralokinumab where there was a phase of the trial where they took people from 2 weeks to 4 weeks, and a good chunk of people do end up holding before falling back. I think there’s so much heterogeneity with the disease, it’s going to come down to, like what you said early before we talked about all this, patient selection is going to be key for everything when it comes to our atopic dermatitis therapies. Maybe this is where the real proof of matching the right patient to the right treatment is going to work out. I think that’s going to be the most interesting thing we all work on over the next decade.

I’ll leave you with 1 more question, Peter, it seems like given safety, efficacy, the ages of approval, dupilumab seems to be a very feasible and real treatment that can be used in the long run for many patients. Are there medications you would not use or you would have more caution for as a chronic treatment for your pediatric patients with atopic dermatitis, some of the other options we talked about that you might use a little differently compared to dupilumab?

Peter A. Lio, MD: Definitely.I feel like if we have to go long term, and I’m defining that over years, more than a year or two, I do feel that our biologics are probably the best bang for your buck. They’re more likely to be safer in the long term because we have longitudinal data; we have 3-year, 5-year, and even some 7-year data that are already being published. That’s exciting stuff, that helps me. For our broader immunosuppressant agents, for example, cyclosporine, a great drug for many patients, but it’s not optimized for long-term use unless you are up against a wall. Typically I take the recommendation of PeDRA [Pediatric Dermatology Research Alliance], which years ago made that point. We try not to keep people on it for more than a year. My goal is 6 months and I want people already coming off, sometimes even 3 months if they’re doing well on cyclosporine. I want to be thinking about other options. Obviously, prednisone, we talked about it, I wouldn’t want to do that for more than little bursts if need be. Same for methotrexate, 1 to 2 years of use at most. Mycophenolate, in the right situation, may be the safest of the traditional ones, so maybe a year or two. But again, with long-term immunosuppression, we see all of these risks.

Now, our JAK inhibitors, where do they fall? My sense is that I would prefer to minimize them when we can. I think a year or two would be a reasonable time to think about other options for most patients. But that being said, as we’ve heard today, for some patients, these really are the only thing that has worked or the most dramatic thing. I don’t want to take that away from a patient. I’ve already had a patient, all of us I’m sure have started people on JAK inhibitors before they were actually approved. So we have people who are now on it for a year or two. I have an older gentleman who I keep asking, “Can we come off of it? Can we tinker with it?” And he says do not mess with it. He’s like, “I’m living my life the best ever, my blood work is fine, I feel great, please, don’t tinker.” You know what, I say OK. I don’t want to push him. So he is kind of a long-term user of an oral JAK inhibitor, and thank goodness he’s doing great. I hope it stays that way.

I think for most patients, I’m going to try to at least start planting the seeds. Can we think about coming down? Can we do other things? Even if it’s rotational therapy. In the old days, for psoriasis, that’s what people used to do. Maybe you would do 6 months or a year on one, take a break from that and try something else for a while, and then we can always go back to it. I like to give the body a break.

Transcript Edited for Clarity