Dupilumab Provides Therapeutic Relief For Patients With Erythrodermic Atopic Dermatitis
In this video, Amy S. Paller, MD, discusses the efficacy and safety of dupilumab for patients with erythrodermic atopic dermatitis (AD), what these results mean for patients with severe AD, and how her study's findings impact specialties beyond dermatology.
- Paller AS, Silverberg JI, Cork MJ, et al. Efficacy and safety of dupilumab in patients with erythrodermic atopic dermatitis: a post hoc analysis of 6 randomized clinical trials. JAMA Dermatol. 2023;159(3):255-266. doi:10.1001/jamadermatol.2022.6192.
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Amy S. Paller, MD is Chair of the Department of Dermatology at the Northwestern University Feinberg School of Medicine, and a pediatric dermatologist at the Ann and Robert H. Lurie Children’s Hospital of Chicago
Amy S. Paller, MD: Hi, I'm Amy Paller. I'm professor and chair of dermatology at Northwestern University Feinberg School of Medicine, and a pediatric dermatologist at the Ann & Robert H. Lurie Children's Hospital of Chicago.
Consultant360: What was the impetus for this study? Why now?
Dr Paller: We've seen a lot of studies come out about dupilumab and really it has revolutionized our care for patients with moderate to severe atopic dermatitis. But really all the data that we're seeing looks more at the mean of that population of moderate to severe. This was a paper that really looked at the most severe patients in that population, pooled from six randomized clinical trials. These patients had what was called erythroderma, which of course relates to widespread erythema or redness of skin. The criterion was that one had to have at least 90% body surface area affected by the atopic dermatitis. So, we're really looking at the toughest patient population specifically to ask the question of whether that patient population did as well as the mean of the population of moderate to severe.
C360: How does this study fill a current gap in our knowledge?
Dr Paller: Even though in each study this might not have been the majority of patients, there were enough when one pulls six trials to be able to look specifically at that population and then think about that in the context of the overall results from these trials. Fortunately, these patients with the most severe, the erythrodermic atopic dermatitis did just as well with respect to their response to the dupilumab, suggesting that even these most severe patients can do well and that one can feel comfortable starting with this medication as a first line agent in these severely affected patients.
C360: What are the knowledge gaps that still remain, and what kind of research can fill those gaps?
Dr Paller: Well, I think there are two things to bring up. One is that, interestingly, this patient population did seem to have a higher risk of developing the ocular surface disease that can be induced by the dupilumab therapy. It's not clear at this point exactly what causes it, but there is a prevailing theory that the goblet cells are deficient in patients who are on dupilumab therapy because interleukin 13, perhaps interleukin 4 as well, tend to be important in the homeostasis of these goblet cells that moisturize our eyes. We're only seeing this ocular surface disease in patients with atopic dermatitis, not with the variety of other disorders for which dupilumab is now either approved or in trials. And that suggests that our patients with atopic dermatitis, and perhaps more so, these patients with the most severe disease, have an inherent conjunctivitis, an inherent ocular surface disease that we're not really appreciating clinically, but that is exacerbated by the treatment.
I think that one unmet need is to really understand that better and understand why that was greater in this patient population. The other issue I want to bring up is the term erythroderma. Now, we're talking here specifically about erythrodermic atopic dermatitis as defined by that at least 90% body surface area involvement with the erythema of the disease. But there is a differential diagnosis of those who have erythroderma. In young children, for example, it can even be immune deficiency and a variety of other genetic and immune mediated disorders. In adults, we have to think about cutaneous T-cell lymphoma, and there's been some evidence that dupilumab in that group will initially look like it's helping, but then these patients have an exacerbation with continued use. So, I think this also raises the very important caveat that when you have someone who has erythroderma, it might be erythrodermic atopic dermatitis, and therefore do very well with dupilumab, but there is a differential diagnosis for physicians to consider.
C360: What specialties are impacted by this study beyond dermatology?
Dr Paller: We're certainly not just talking about dermatologists who manage these patients. They might be seen by primary care doctors, especially if there're not a lot of specialists in the area, certainly by allergist. As I mentioned, this increased risk of ocular disease pulls in the ophthalmologist. And then when we're considering the differential diagnosis of erythroderma, we can have immunologists involved, we can certainly even have oncologists involved.
C360: What is next for this patient population and this treatment option?
Dr Paller: This patient population certainly is one that is benefiting greatly from the interest or in the past several years in finding new therapies for this very common heterogeneous disorder, atopic dermatitis. So, I'm very excited about the fact that we're not just seeing dupilumab, which was the first one out of the gate, but other biologics, JAK inhibitors, and perhaps more to come.
We also are certainly interested in expanding the use of these new medicines as a whole and repurposing them for other indications. Of course, dupilumab itself has been out for a while, including for asthma, eosinophilic esophagitis, and prurigo nodularis very recently, more in the works in terms of testing that the range of type two immune disorders, others as well coming out. For example, the JAK inhibitors are going to turn around how we might treat immune mediated skin disorders, like alopecia areata and vitiligo. In addition, a wide range of other disorders that are not dermatologic, but involve immune mediation. We might even be able to broaden the use of dupilumab or other inhibitors used for atopic dermatitis for the wide range of itchy disorders that aren't atopic dermatitis. These are all emerging uses and active investigations.