Experts in dermatology review the indications and evolution of the use of dupilumab in patients with atopic dermatitis, highlighting its recent approval for patients 6 months and older.
Raj Chovatiya, MD, PhD: I want to make sure we have enough time to talk about some of the more recent updates when it comes to biologic therapy and dupilumab. What I want to focus on, and I’ll have Peter start and then I’ll jump back to you Brit, is…since the point of approval for adults, we’ve had a phase 3 trial in pediatric patients from ages 6 to 11, we had a phase 2 study in 6 months to 5 years, then there was this open-label extension in phase 3, looking at people 6 months to 18 years old. Maybe you can walk us through the evolution of these studies looking at dupilumab and what we’ve arrived at now.
Peter A. Lio, MD: It’s been quite a journey, hasn’t it? When it first was approved in March of 2017, it was for adults only. Initial approval was for 18 and up. And of course, we know so many of our patients are under 18. So already I think there were people dabbling in it. As we’re used to, particularly in pediatric dermatology, almost everything we do is off label. So, anybody who gets too sanctimonious about it, well find me anything on label for half the stuff we treat. We got the first drug approved for alopecia areata this year. These conditions have been timeless, and here we are.
That being said, we had adults only at first, and then we got the adolescent data. I think that was a breakthrough to see the 12- to 17-year range get approved. That really opened the door. Then of course, we got our pediatric data in 2020 for 6 years to 12 years. So we’ve watched it go lower and lower and lower. I’m really proud, and this is a little bit of a plug for the nonprofit patient group National Eczema Association [NEA] of which I’m a board member. That’s a nonpaid position. In fact, I’m a proud donor to NEA. They played a role, I really believe, in pushing the FDA in advocating to get more options for children because the historic approach from the FDA has been approve it in adults and if it goes well, we can then look at pediatric trials. I think now we’re seeing this renewed emphasis on getting stuff for these children who need it because we used all these things off label and that’s not the best medicine. We really want studies that are looking at this population. The great news is when we finally got this approval down to 6 months of age, what I love is that not only did we see the efficacy data for all of these different age groups, but also we have all the safety data. A bit of the spoiler alert is that thankfully it’s all pretty comparable, both safety and efficacy across all these different age groups is pretty similar. So that makes it a relatively easy thing to talk about. One could imagine a multiverse where in 12- to 17-year-olds we saw some weird stuff, so there might be some issue, but thankfully at least with dupilumab, we didn’t see it for this indication of atopic dermatitis [AD].
Raj Chovatiya, MD, PhD: Isn’t that wild that it’s almost in some ways boring to talk about, but exciting, because there isn’t actually anything new in the best sense of the word. I can compare the data from each of the age groups side by side, and here’s another safety table that largely looks pretty good, and here’s the efficacy that largely matches. I can’t think of that many medication examples where not only we managed to march so progressively in a linear fashion down to younger ages, and the data were so consistent. Can you think of an example of that?
Peter A. Lio, MD: It was crazy. It’s kind of a dream for a company because you don’t want to be interesting, just like when you’re a patient, you don’t want to be an interesting patient, you want to be boring, stock standard, by-the-book. Give me this simple treatment and it works. You don’t want to have an interesting drug because that means something weird is happening. Although I will say, from our standpoint, when dupilumab first launched, I was excited. I thought that this is going to help us separate some of this heterogeneity. Maybe there will be a group of super-responders and nonresponders, but even that has been kind of boring. Most patients really do respond pretty well. It’s been much fuzzier than I expected and even, frankly, surprising. Seeing that it now has several other indications from asthma to eosinophilic esophagitis [EOE] and to chronic sinusitis, it tells us that this is a broader allergic disease pathway-focused treatment. Even some of the stuff that seems quite different, like bullous pemphigoid, there’s some research on it. So I’m even surprised because early on if you would’ve asked me, I would’ve said no, it should stay just in this domain, but it ends up being broader than we thought. I think that’s a good thing for all involved.
Raj Chovatiya, MD, PhD: It’s very much like what we saw with psoriasis for 20 years. In real time we got to learn, this is how important TNF [tumor necrosis factor] is, this is where IL-17 [interleukin-17] is working in the pathway, this is where IL-23 is. In some sense, we started at a point of not only high efficacy, but we learned that thinking about Th2 [T helper cell type 2]-driven immune pathways is actually important across most people with this disease, but also across a bunch of other diseases that we may not have even thought about. Urticaria is one of those, or whether it be prurigo nodularis, or as you mentioned bullous pemphigoid. I know there is more exciting news to come there, but to swing it back to children, Britt, what’s the significance of dupilumab being the only approved, targeted, FDA treatment for this 6-month to 11-year-old population?
Brittany G. Craiglow, MD: I think this is going to go down as one of the biggest game changers in dermatology ever. It has changed not only the way we treat atopic dermatitis, but the way we think about these patients, the way we think about therapy, the level of disease that we tolerate or don’t anymore. For me, I said to my nurse the other day, “What did I do before this medicine? What did I do?” Sometimes I’ll say I miss my children with atopic dermatitis because they’re doing well. I’m not seeing them, they’re not calling because they’re flaring, or they’re not coming in every 2 months. Once they’re doing well, I see them maybe every 6 months. I think it is so game changing. We know to your point, the other indications, a lot of our children with severe AD, they have asthma, they have EOE. I have a patient who is 7 years old, at the start she had AD, EOE, and asthma. She came back happy as a clam and said, “Dr Craiglow, I ate Thanksgiving dinner all the way through for the first time.” We get to see these cases. I started to treat her for her skin, which she’s thrilled about too, but she’s reaping the reward in all these different ways. It is so dramatic and so rewarding too.
I always say yes, the conversation takes a little longer; it doesn’t take as long as a JAK inhibitor or cyclosporine, but it takes a little bit longer. There is an investment in time on our part in the room, but if people do well, it’s such a pleasure. We all went into this to help people, and it feels good and patients’ lives are being dramatically changed. These children are sleeping, and all of a sudden they’re getting fewer skin infections. We see that. Dupilumab is cutting skin infections by half in this population. As Dr Lio mentioned earlier, are we maybe going to be able to change the natural history of disease or interfere with this atopic march? Maybe. I think it’s so exciting, and I think there are so many patients who, it sounds sort of corny, but they’re going to have a different life from what they would have pre-Dupixent [dupilumab].
Transcript Edited for Clarity