Expert Perspectives on Collaborative Management of Atopic Dermatitis - Episode 15

Role of Disease-Modifying Therapy in Atopic Dermatitis

Lawrence F. Eichenfield, MD, Rady Children’s Hospital-San Diego

Rady Children’s Hospital-San Diego

,
Peter A. Lio, MD, Northwestern University Feinberg School of Medicine

Northwestern University Feinberg School of Medicine

,
Elizabeth A. Swanson, St. Luke’s Children’s Hospital

St. Luke’s Children’s Hospital

,
Jeffrey M. Bienstock, MD, FAAP, PediatriCare Associates

PediatriCare Associates

Examining the potential role for biologic, dupilumab, in the treatment of moderate to severe atopic dermatitis.

Lawrence F. Eichenfield, MD: I’ll start with the advantages and the background. We have dupilumab. I explain to patients that we’re trying to dampen inflammation in atopic dermatitis. That inflammation is in the skin, but you can also find it in the blood. With topicals, we’re treating outside in, but sometimes the inflammation is so bad that it’s nice to treat from the inside out. That desire was to be able to dampen stuff down without a lot of other effects.

I go on. I have a variety of analogies. My favorite is that I’m trying to turn off a lamp in a living room that’s next to a kitchen. I want to turn off just that lamp. Using oral corticosteroids as the analogy, I’m turning off electricity for a few houses in the cul-de-sac. The lamp does go off, but I’m turning off a lot of other stuff as well. What we really want is a much more selective switch that’s not going to take out a lot of the immune system with it.

Dupilumab is an IL-4 receptor blocker. It blocks the IL-4 and IL-13 cytokines. What’s nice is that it’s not like a systemic immunosuppressant agent that has a very narrow set of adverse effects. It has a major advantage in that it can bring long-term disease control to a great percentage of children. It started as first being approved in adults, then approved for 12 years of age and older, and now it’s down to 6 years of age and older. It’s being studied in active trials right now for patients 2 to 6 years of age. In the 6- to 12-year-old group, 75% of patients get 75% better after 4 months. Depending on the individual, they’ll be clear or almost clear. Within a few months, 40% of those patients become clear or almost clear. 

It’s a different kind of therapy that I don’t like to use. It’s an injection that’s given every 2 weeks or every 4 weeks depending on the patient’s age, dose, and weight. It’s not a drug that we like to stop and start because it’s a synthetic antibody. As I tell my patients, when you give a synthetic antibody the first time, the body sees it and it goes, “Look, there’s an antibody there.” And it’s cool with it. The antibody blocks the inflammation from happening and cools down the eczema.

But if you stop it for a while, like a few months, and then do the antibody injections again, there’s a chance that the body is going to go, “I’m not sure this thing is really part of us; let’s attack it.” Then you can get antiantibodies. You get this antibody response neutralizing antibodies, which can make the drug not work. 

For this drug, I like people who are willing to change their lives, generally for a year or 2, with a plan to get injections every 2 weeks or 4 weeks after the loading dose, depending on their particular weight tier. It’s been absolutely revolutionary.

Let’s look at the adverse-effect profile. You can see conjunctivitis in about 10% of individuals over time. That’s something to keep an eye out for. We’ve been much more conscious about periocular disease and conjunctivitis from this. You have to be careful about avoiding live vaccines. There are some rare adverse effects that we’re seeing in some patients: psoriasiform dermatitis, a persistent facial dermatitis. But it’s been going for years in adults, and they haven’t had to change the safety labeling, which is incredible given the numbers of patients treated with it. It’s been quite revolutionary for our more severe kids, adolescents, and adults.

Lisa, do you want to weigh in with your thoughts?

Elizabeth A. Swanson, MD: Yes, I would like to chime in with 2 quick thoughts. First, when I’m talking with patients and their families about dupilumab, I describe it as a life changer for the patient, their family, and their doctor. It makes me grateful to be practicing medicine at a time when we can offer these therapies to our patients.

My other comment is about duration of therapy. One of the most common questions I’m asked at that initial conversation about starting dupilumab is: How long will my child need to be on this? Once they’re on it, I never hear that question again because it is so life changing. People realize they don’t want to go back to the days before Dupixent. I address that question at the initial visit by saying, “We’ll think about that later, but this is ongoing therapy.” Once they’re on it, they realize the value in it, and everybody feels better.

Lawrence F. Eichenfield, MD: I should mention that the drug is also approved for eosinophilic asthma for patients age 12 and older. It’s also approved for nasal polyposis associated with rhinosinusitis. That’s 1 of the issues you have to deal with, because if you have a patient with asthma and atopic dermatitis, it can really improve their asthma. You don’t necessarily want them stopping their asthma medications. That’s part of the counseling that we need to do. Whoever is prescribing those medications should be aware of it.

It also means that more than 1 disease that patients have can be treated. It’s a tremendous benefit for many of the patients who do have these recurrent allergies. Other atopic phenomena are being studied with dupilumab as well.

Peter, you have extensive experience with adults as well. How do you consider dupilumab? Do you think it’s disease modifying? How do you assess its place in therapy?

Peter A. Lio, MD: The longer it’s been out and the more experience I have with it, I’m shifting to trying to use it earlier in the disease course. It’s interesting, because there is this feedback loop within the understanding of the disease so we can treat to target something similar to what’s been going on with psoriasis for quite some time.

In the old days, my teachers used to talk about an old commercial on television about psoriasis that would say “the heartbreak of psoriasis,” because you didn’t have much you could do for it. Now if you look at the National Psoriasis Foundation treat-to-target goals, it’s clear or less than 1% of the time. 

For atopic dermatitis, that has simply not been the case because we haven’t had the tools. But now we’re starting to say, “Why should somebody be struggling with topical steroids over 30%, 40%, 50%, 60% of their body, which becomes incredibly challenging?” You’re slathering yourself in all this ointment all the time to try to maintain control. You’re walking that fine line between safety and efficacy when we could potentially, for at least the appropriate patient, use a systemic agent that can get better control, including of the invisible or nonclinical areas that we know still have inflammation.

I’ve increasingly lowered my threshold for starting it with really good results. I suspect there may be a disease-modifying aspect to this drug. I’ll even say a little more broadly that getting good control, no matter what the means, can lead to a disease-modifying aspect. This is just another tool in our toolbox to do it. 

We put together a paper a few years ago in which we had a number of patients, generally with quite severe atopic dermatitis, who did very well on dupilumab and stayed on it anywhere from 3 months to a year. When they were doing well, for varying reasons, they came off. Sometimes it was because of eye issues. Sometimes it was because of travel, trying to get pregnant, or many other things. So we stopped them from the medicine. 

I followed those patients. What we found in this very small anecdotal series was that not a single patient in that group had a rebound. With prednisone or something, you’ll sometimes see them get worse than they previously were when they come off. Nobody rebounded. Nobody even got back to their baseline. We called it a relative remitted effect. By no means were they cured, but it was much better. It was in a remission state.

I really think dupilumab, among other treatments, can do this for the right patient, particularly 1 who’s doing well. I use that information because, as Lisa said, a lot of patients will say to me, “Is this forever? Is this going to be like insulin and I can never come off?” I say, “Not necessarily. Let’s get you better for a long time. I want to get everything back in a virtuous cycle instead of this vicious cycle.” Then it may be possible to space out or even take a break, with the caveat that we potentially could run a risk of developing drug-neutralizing antibodies, as Larry said, or becoming sensitized to the medicine. 

Lawrence F. Eichenfield, MD: We clearly don’t know how many go into sustained remission if we start it early and we do so many years of treatment, but we believe that’s going to happen. We just need data.

I want to mention something about the safety profile. We don’t expect primary care doctors or pediatricians to be writing dupilumab or other biologic or oral JAKs in the future, which are other systemic agents.

One of the big issues is blood testing before you get started and the frequency of blood monitoring. The really nice about this drug is that none is required. As it went through its approval process, both adults and down to young kids as well, now for 6 years of age and older, there is no need for any baseline blood work. It doesn’t affect cell line significantly enough to need to do any particular blood work. There were recent data presented of longer-term laboratory data in the younger kids as well. That’s incredibly nice.

With our other systemic immunosuppressants that we use—some are oral—you need blood work all the time because you’re worried that methotrexate could wipe out your bone marrow, could cause liver disease, etc. There’s no need. That’s something patients get when you mention that to them. The drug appears to be safe enough that we don’t need to do any blood work monitoring. 

I know some specialists who will do general health blood work in patients prior to starting dupilumab. They may assess to make sure they don’t have steatotic liver disease if they’re heavy, etc. But for the drug itself, there’s no need for blood testing. That’s something that’s quite nice.

Transcript Edited for Clarity