Atopic Dermatitis: Pathophysiology Driving Management Decisions - Episode 7

Systemic Treatments for Atopic Dermatitis

Emma Guttman, MD, PhD, reviews the use of systemic therapies in atopic dermatitis, including the latest evidence for the monoclonal antibody dupilumab.

We have our baseline recommendation of avoiding things that are irritating, and using a gentle general approach with moisturizers to help keep that barrier strong, and our topical corticosteroids as a first-line therapy. I often call that a reactive therapy. If the patient is flaring up, we use our topical steroids, but then we have several nonsteroidal agents like the topical calcineurin inhibitors [TCIs] and the phosphodiesterase [PDE] inhibitor to maintain or to be used in medium-term or long-term management so that we’re not overusing our steroids.

Let’s say we’re doing all that. Emma, you then get there, and the patient comes back and says, “It’s not enough; I’m still pretty miserable” or much more commonly, “I’m needing steroids all the time. The PDE4 and TCIs are just not enough for me; I’m still miserable.” What do you say then? Where do you go next?

Emma Guttman, MD, PhD: Next, I would go to a systemic approach, and I am also often judging this by the body surface area. Sometimes, when I see a patient with 20% or 30% of the body surface area involved, I will always give them topical agents first. And I am telling them up front, I say, “Let’s see you in a month or two because if that’s not enough, then we will ultimately need to go for some systemic medication.” When I then talk about the systemic medications, I tell them what we have available. I tell them that we have phototherapy, depending on the physician and if they have phototherapy in their office. It also depends on the patients. For some patients, phototherapy is safe, but some patients would not like the idea of coming to the doctor’s office 3 times a week. For many patients, it’s not feasible.

I then tell them that we now have approval of a new biologic that changed the game for atopic dermatitis. It’s a safe drug, and you don’t need to do blood work as we need to do for the immune suppressants. I tell them that, in atopic dermatitis, we know that we need to spend some time with patients because we need to explain. After that, they will often decide one way or another, and we do a trial. Even after phototherapy sometimes, I have quite a few patients who, after phototherapy still decide that they want to do dupilumab. It’s still a discussion with the patient to lay out all the options, and it’s an informed decision with the patient.

Peter A. Lio, MD: That’s a perfect segue to our next question, which is going to be this: can you tell us a bit about the evidence and the mechanism of action for dupilumab and talk us through what the data have been so far?

Emma Guttman, MD, PhD: Yes. Luckily, I was involved with dupilumab almost from the beginning, I was involved with the first study in terms of the mechanism. My laboratory [at the Icahn School of Medicine at Mount Sinai Medical Center] investigated the mechanism of action of that study; I was not involved with the clinical site myself, but I was involved in clinical trials in phase 2 and phase 3. I was also involved in the mechanisms of action, and my lab did the mechanism of action of dupilumab. It was clear right from the beginning that the drug works because we could differentiate patients for whom the drug works vs those for whom it didn’t work. Sometimes, you do not know who is on placebo and who is on the drug. Here, it was quite clear.

Seeing it in practice, we have many patients who were in the trials. I’m talking about trials that were 8 or 9 years ago, and they are still on the drug. For me, that is showing that, first of all, it’s safe. The patients continue to respond over time, so the drug didn’t lose efficacy. We know that it sometimes happens in psoriasis. They are happy, and it changed their life.

I have a patient who said that he was 100%, meaning that he was 100% covered with eczema. Now, you cannot even tell that he has it. It changed many lives. It’s now approved for atopic dermatitis in adults and adolescents. We now also have the pediatric approval for patients aged 6 to 11.

The beauty of it is that you don’t have to do blood work. That’s something that physicians and patients like. You also don’t need to see them every month because you don’t need to do any blood work. Taking away that blood monitoring that we all feel is a pain with the immune suppressants is an important thing for us and for the patients.

In terms of patient selection, the type 2 immune axis is upregulated in all the patients. It is possible to use dupilumab in all the patients. Of course, there will be patients for whom dupilumab may not be enough, and there are also some patients for whom dupilumab doesn’t work. That’s the minority of patients; for the majority, it works really well.

Peter A. Lio, MD: Thank you. Linda, are there patients who you can pick from the beginning and say, “I think this patient’s going to need a systemic approach” from the moment they walk in the door?

Linda Stein Gold, MD: Yes. What we have to realize is that, when a patient walks in, we are seeing a small snapshot in their life. I always say to them, especially if it’s a new patient, “How many days in the past month have you been clear?” Some of them are going to say, “You know what, I just put a new body cream on, and I just flared up. I’m always clear, but now I’m just terrible, and it just happened this past week.” Then there are other patients who look at you with a strange look on their face. They don’t understand what you’re talking about and say, “I’m never completely clear. Sometimes I’m not bleeding, but I’m never completely clear.” Those are the patients for whom you have to understand how they live on a day-to-day basis and gauge that at the first visit. Sometimes, I’m surprised. Even when I’m doing these clinical trials and start somebody on a topical agent who has horrible disease, we put them on a steroid but give them enough medication, they come back and they say, “I’ve never looked so good.” I’m thinking, “This was nothing. This is a regular steroid. I can’t believe you look so great.”

Some of it is compliance, and some of it is the maintenance; this is a chronic disease that needs chronic maintenance therapy even when they’re not flared up. There are those patients for whom I feel like our job is this: when a patient has moderate to severe disease, their disease is front-and-center every single day all day. Our job may not be to get rid of it completely but move it to the back of their mind so some days they don’t even think about it. They live a regular life where they can say, “Oh that’s right, I have it,” but it doesn’t come up every minute of every day. For those patients, I’m thinking about it as soon as they come in.

Peter A. Lio, MD: It’s true, I will often say that there is a cost to not treating it as well. There are risks of course to all the medicines and treatments we’re talking about, but there is an enormous risk to not treating. The impact is huge.

I have an interesting setup because my focus is a bit more on integrative care. I have some patients who come in and say, “I’m not using steroids.” From the very first visit, they say, “I’m not using any Western drug.” For me, that’s tough. It’s sometimes like fighting with both hands behind your back. I don’t know what we can do, but that is one of my favorite times to use phototherapy. I probably use it a lot because I have this population. I say, “We’re going to then rely upon the healing power of light.” Maybe 75% of the patients get significantly better on phototherapy, but the issue is that it’s expensive, even when it’s covered. They often have a co-pay that goes with it, and there’s a time issue. The mechanics of getting to the clinic, parking the car, and coming up and getting the treatment are what makes it so tough, but I love those certain patients.

The thing I often find is such a good predictor of whether phototherapy is going to work is if the patient says that they get better when they’re out in the sun. It sounds obvious, but if they are the people who are better in the summer, they’re better when they’re on vacation someplace warm, and they’re worse in the winter, you have a high likelihood of getting them better.

On the flip side, we have those patients, and it’s always fun when I talk to other dermatologists in Florida and places that are more humid than up here in Chicago, they’ll say, “You guys say that it’s always during the winter that it’s bad, but we have lot of people who say that, when it’s hot and humid, they are miserable.” I feel like it almost does require a slightly different approach. Sometimes we’ll recommend the heavier things, and some of these treatments can exacerbate it. It’s fascinating to see these personal preferences. You’re right, we have to get the patient fully on board if they’re going to use the treatment.