ֱ brought together three expert leaders for a virtual roundtable discussion on atopic dermatitis: Moderator Peter Lio, MD, of Northwestern University Feinberg School of Medicine in Chicago, is joined by Linda Stein Gold, MD, of the Henry Ford Health System in Detroit, and Alexandra Golant, MD, of the Icahn School of Medicine at Mount Sinai in New York City.
This final of four exclusive episodes explores how to approach modifying, pausing, or discontinuing atopic dermatitis treatment. Click here to watch other videos from this roundtable series.
Following is a transcript of their discussion:
Lio: And that brings us to our final question, which is really about maybe the best thing that can happen to our patients in some ways. When they're doing great for a while, and this comes up -- I think it comes up at the very beginning of therapy because patients often say, "So is this forever? There's no endpoint? I'm going to be on this for life?" And usually I say, "Not necessarily. You may be able to come off or come down at some point, so let's keep that in mind." But the best day happens when they do that 6-month follow-up and we say, "How have you been?" "I've been great, I haven't had any flareups. I'm not even using any topicals. I'm feeling awesome. Doc, what do you think? Could I take a break from this?"
How do you guys approach it, Dr. Golant, when you have a patient like that, what do you usually say? How do you make that decision?
Golant: That's also been evolving. I think sometimes patients do the experiment on their own, especially with the biologics where they just start... there are patients we know that need it probably more than the approved dosing regimens. And there are definitely patients that need it less, but I think sometimes they tell me, and oftentimes they do not.
But those are the patients that go longer than you know you've given refills and they see you back in a year and you're like, "How did you use 6 months of medications over a 12-months period?" It's a really interesting topic. And will we learn one day that if you treat for a certain duration, then you can kind of give patients a drug holiday and see some type of durable remission? I think the population we'll learn quickest that answer from is the pediatric population because that's also a population that has just changing nature of disease without drugs sometimes.
I always say, let's get you clear and then let's revisit the conversation. I'm not opposed to patients trying to stretch out that window. We know from the trials, at least on approved dosing, there didn't seem to be drug-drug antibody formation. So I am usually happy to do the experiment with them. I'd be curious to know what the two of you do as well.
Stein Gold: So just to comment on that too, I think we're learning so much and maybe the most interesting data looks at lebrikizumab, when we looked at their long-term data of what happens when, after you get these patients clear, almost clear, and then you stretch out the dosing or you go to placebo. And we saw that there was a significant number of people who maintained efficacy over the course of the rest of the year. So that tells us that we might have some flexibility there. Maybe we only have to give them injections twice a year. Maybe they need once a year like a vaccine or once-a-year your flu shot, maybe once-a-year your biologic, I don't know. But I think we're going to learn a lot as these drugs are available and as we see patients kind of fool around with it a little bit, stretch it out a little bit more.
I think with the JAK [Janus kinase] inhibitors though, we don't maybe have the same kind of flexibility or dosing possibilities. We've seen, at least in the clinical trials and in actual practice, that they do amazingly well while they're on drug. But for some of my patients, if they miss, if they stop taking their JAK, I think some of them start to feel itchy within a few days. They start to notice something's going on. That's why they tend to be very compliant with their medication because they feel it when they're not.
So I'm not sure. We've seen with some of the data that maybe about 20% or so of patients can go off a JAK and still maintain that efficacy, but the majority do start to lose response within those early weeks to early months. So I really think that a patient has to be completely clear before I would consider maybe stopping their JAK.
Lio: It's such a good point. And I often feel that -- and I don't know if this is really a rule or a law or just sort of an observation with our relatively limited data -- but it's that medicines that work more quickly, that are faster on and off, so I think about our systemic corticosteroids, our JAK inhibitors, they're very fast on and off, they seem to have the highest risk of rebound or relatively rapid flare of disease. Whereas the slower medications seem to give you a little bit more remittive. And it's fascinating. I think our biologics and even to some degree, cyclosporine. I mean in the old days there was a little bit of a literature on relative remission or being able to have some quiet time. Of course, phototherapy as well. I view as a generally remittive therapy, you get people better and you take a break and they often stay better.
But I would love to fine tune this. I'd love to be able to figure out how can we optimize it for patients? How can we get the highest number of patients on the lowest dose of medicine, overall? And that's been challenging.
But I agree. I have the same thing where patients, if they miss a day, they say, boy -- or even I have a woman, she was telling me this a couple of weeks ago. She said she takes her JAK inhibitor in the morning and she said sometimes at bedtime she's starting to feel itchy. And I thought, wow, I see you're definitely not ready. You're barely holding off as you're getting to the lower doses. Crazy.
Golant: I was just going to add, I think that's really the next frontier for atopic dermatitis is I think, disease-modifying, or is there the possibility for disease modification? We start to see I think a hint of it if you look further down the pipeline to the OX-40 inhibitors, but that I think is going to be very, very interesting. Not only what it does for atopic dermatitis, but also what it does in our younger patients for the rest of the atopic march, rates of asthma, seasonal allergies, what happens to those?
Lio: I love it. And I think there was that paper that came out just in the last year where they did an atopic dermatitis prevention study where they vigorously treated in the first few months of life and they had an outlier -- an outcome measure, actually -- looking at egg allergy. And they showed that they were able to decrease the egg allergy by treating the disease. So I love this concept that by treating it, you may not just treat eczema, which is important by itself, but we may actually be modifying other allergic comorbidities. And, for sure, we're going to be modifying sleep in some of the psychological pieces because some of those are driven by the skin. And to me that's huge. I think that might take longer for those to stick if we can't be as fast on those, but I do think that we can make a difference.
Dr. Stein Gold, do you find that your patients who have a behavioral component or sleep, this impact on sleep -- do you find that that often takes longer even though their skin maybe has been better for weeks or months, that some of those other pieces have a longer echo before they actually improve completely?
Stein Gold: It's interesting. Sometimes I even see it the other way. Their skin might still look disastrous, but they'll say to me, "I slept through the night," and so that is huge. And I worry so much about our kids who have severe disease. Imagine sitting in middle school trying to pay attention to a complicated math problem and all you want to do is scratch your skin off. Their education is suffering, their social life is suffering, their family life is suffering.
So it's huge. And so even seeing just an early onset of itch that helps with the sleep, that helps with all the other aspects is absolutely critical.
Lio: Well, this has been amazing. Thank you both so much for chatting with me today. What an exciting time to be focused on atopic dermatitis, both for the patients and for us. And thank you to the viewers. Thank you so much for joining us. We really appreciate it.