Efficacy and Safety of Upadacitinib for Atopic Dermatitis Treatment

EP: 1.Pediatric Atopic Dermatitis: Pathophysiology, Prevalence, and Symptomology

EP: 2.Atopic Disease Heterogeneity and Physician Awareness

EP: 3.Considerations and Comorbidities Affecting Atopic Dermatitis Diagnosis

EP: 4.Role of Atopic Disease Burden Across Different Life Stages

EP: 5.Pediatric Atopic Dermatitis Treatment Landscape

EP: 6.Defining Treatment Success in Patients With Atopic Dermatitis

EP: 7.Nonpharmacological Approaches to Treat Pediatric Atopic Dermatitis

EP: 8.Advice for Curating an Atopic Dermatitis Treatment Plan

EP: 9.Challenges With Available Atopic Dermatitis Treatments for Pediatric Patients

EP: 10.Pediatric Atopic Dermatitis: Considerations and Challenges With Oral Therapies

EP: 11.Overview of Systemic Treatment Indications for Pediatric Atopic Dermatitis

EP: 12.Efficacy and Safety of Ruxolitinib for Atopic Dermatitis Treatment

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EP: 13.Efficacy and Safety of Upadacitinib for Atopic Dermatitis Treatment

EP: 14.Recent Advances for Dupilumab Use in Pediatric Patients With Atopic Dermatitis

EP: 15.Dupilumab Dosing Considerations for Pediatric Patient Populations

EP: 16.Evolution of Treatment Selection for Pediatric Atopic Dermatitis Management

EP: 17.Emerging Therapies and Future Directions for Pediatric Atopic Dermatitis

EP: 18.The Importance of Patient Education in Atopic Dermatitis Management

Raj Chovatiya, MD, PhD: I’ll transition to another JAK inhibitor, and this one is an oral medication, the only other one that has a specific pediatric indication. We’re talking about upadacitinib. Maybe you can tell us a little bit about your thoughts, Britt, on upadacitinib and the phase 3 trial program and your takeaways in the real world.

Brittany G. Craiglow, MD: It made our lives so much easier. I joke that dermatology is going to be boring in few years because we’re going to have all these choices for everything. You don’t do well with this, we can move on to that. Raj, as you pointed out, this is a medicine that is going to be second line. In my opinion, it’s a pretty hard sell to make this a first-line medicine for atopic dermatitis [AD], beyond topicals, obviously, unless someone has a comorbidity that might respond well to a JAK [Janus kinase] inhibitor. That would be the caveat there. In most of our patients who are candidates for systemic therapy, dupilumab is going to still be our first line. But we know that while a lot of patients do very well with it, it can be life-changing, there are some patients who don’t get all the way there, and who don’t respond. Now all of a sudden we have another option. I would say an oral therapy is very nice. It’s something that you do have to think about every single day instead of every 2 weeks or every 4 weeks, but we know how much patients love needles. So that can be welcoming for a lot of our patients and their families. There is some laboratory monitoring with these drugs, so that is something. There are a few needles involved. In terms of that, it’s similar to what we’re used to with other biologics, like the psoriasis biologics. The one addition would be lipids. These labels are interesting. They say checking lipids at follow-up, but don’t usually mention checking them at baseline. You want to do baseline lipids, in my opinion, because if you don’t know where they started, you have no idea how to interpret their lipids at 8 weeks or 12 weeks.

JAK inhibitors orally are like prednisone for a lot of people with atopic dermatitis. They work fast. We saw that in the trials.¼I actually had a dad text me the other day who started upadacitinib in his 12-year-old who had failed dupilumab. Three days into treatment he’s sleeping through the night, and he hasn’t slept through the night his entire life. The dad doesn’t know if this is actually possible. So sometimes it can be kind of like magic, and it’s really amazing that we have this option. It’s a different discussion, as Dr Lio mentioned even about the topicals; this is a little bit longer. This is a systemic therapy; there are some risks here. They’re not super high, and probably in our young, healthy patients, they’re even lower, but nevertheless these are not vitamins. I think having a conversation, looking at efficacy data, and working very quickly is important. If you go out to about the 6-month range, you’re pretty close to dupilumab. It may have a little bit better efficacy. But again, remember we have this medicine with no black box warning, the discussion is a little bit different, but for people who fail that, we have this other really wonderful option with more to come.

Raj Chovatiya, MD, PhD: You make a good point. I will say that it is so case dependent. I was just thinking about a patient that I saw recently¼who is erythrodermic from what we figured out to be atopic dermatitis. I think they had been on some oral medications, probably a lot of steroids previously, and he was so hot and so bad we had to get him admitted inpatient. Wet wraps cooled him down, and I think we even did a little cyclosporine. Then came the discussion of what do we want to get him started on. This is a circumstance where I actually didn’t start this patient on biologic therapy, I started him on upadacitinib right away because, as you highlighted, its speed of onset was so important to me. I was worried that anything I pulled was not going to help him fast enough. This is one of those circumstances where it was a unique case, but it’s one of those ideas that we’ve been having through this entire conversation. It’s so individualized in terms of that discussion you’re going to want to have with your patients. I’m pleased to report this gentleman is doing well.

A couple of points to the ones you made. I think the speed of onset is a huge one. Largely you’re talking about 1 to 2 days typically where you can see significant impact in terms of itch in particular, and knowing that itch is tied so closely to sleep, I think that is a big thing. I’ve had similar things my patients have told me. One of the things that’s important for folks to know is that there’s 2 doses of upadacitinib that are approved for atopic dermatitis. The 15 mg and the 30 mg, it was studied in both. On-label you’re supposed to start at 15 mg, and then if you have an inadequate response at any point, moving up to the 30 mg. I’ve been very pleasantly surprised in the real-world patients that 15 mg has done a fantastic job for a lot of them in terms of getting to the point where I have not needed to use 30 mg as much as I was thinking previously. Before there was even a label I was thinking I was going to have to start at 30 mg and go down to 15 mg. That’s been very promising. Additionally, when you pool the measure of 1 and 2 phase 3 data and then do the cuts by looking at the 12-to-17 population and 18 and up, obviously for many of the specific adverse events of interest that are on the boxed warning, there’s the occasional report of 1 or 2 on the adult side. It’s almost 0 in that pediatric cut when you’re looking at the 16-week data. Really quite low when you’re looking at the 1-year long-term extension data. So to your point, different patient populations, kids are not just little adults. There are biological differences as well, so largely we’re probably going to have a more favorable risk/benefit profile when we’re talking about the age group as well. What other thoughts, Peter, do you want to share about your experience with upadacitinib?

Peter A. Lio, MD: The acronym that I use when I talk to my patients about particularly these more intense medicines is EAST: efficacy, accessibility, safety, and tolerability. We go over those 4 aspects of it. This is a situation where the safety is a little bit concerning, but the efficacy, particularly in terms of the speed of onset, is so remarkable that it can be transformative. For many patients, it does outweigh the potential safety risks. My technique for this is usually talking about it early. I bring it up, give them some information, and say I don’t expect you to make a decision on this right now. Why don’t you go home and read and we’ll talk about it. As I did that I also happened to bring in a sample. We had a sample bottle, and I said, take this just in case we do want to start it. As we were chatting the patient opened up the bottle, took a pill with her water. I said “wow.” She said, I am just so ready, and I am so miserable. I think that really fits. Just as you said about that hospitalized patient who was so over it and suffering from all of this that they were ready for a change. For those patients, it can make a difference, and it can be the right choice. That’s the secret of this—patient selection. I never want to push it on somebody because of the potential safety risks. I always want them to come into this discussion in agreement as a shared decision-making process.

Raj Chovatiya, MD, PhD: I’m going to transition here. We’ll go away from JAK inhibitors for just a second. I want to talk about our young kids. There’s a couple of options that have official approvals here. While it’s not completely new, I want to spend a minute reviewing crisaborole, which is approved at 3 months of age per the latest indication. Britt, you can share very high-level thoughts about this data in terms of young kids and how this fits in your practice, and some strengths and weaknesses, before we transition to newer updates in biologic therapy?

Brittany G. Craiglow, MD: It’s interesting. When it first came out, I thought this would be a drug just prescribed by dermatologists, but I find actually it’s prescribed more often by pediatricians. So I do often have patients coming to me who have used it or tried it. I don’t use a ton of crisaborole, but I do think there are certain scenarios in which it can be useful. For sure in more mild patients as a steroid-sparing agent. I tend to like it for hands and feet in particular. Stinging and burning can be an issue, so it’s something you need to counsel about. It’s usually something that patients kind of get over. If you have a really young child I think it’s trickier in terms of are you going to be able to tell if it’s bothering them, etc. As a maintenance for hot spots, chronic hands, and feet are places where I’ll use it. For families who want something on-label, who have concern about topical corticosteroids, it’s a really nice option because we do have that approval all the way down to 3 months. We don’t have that with other medicines. In my practice I tend to see more moderate to severe AD so I use less of it, but that’s not to say that it doesn’t have a role in some patients.

Raj Chovatiya, MD, PhD: I think that that’s a pretty nice encapsulation overview, and I think largely kind of fits my clinical practice.

Transcript Edited for Clarity