How an Atopic Dermatitis Biologic May Affect COVID-19 Infection
A recent study published in The Journal of Allergy and Clinical Immunology: In Practice demonstrated that patients with moderate to severe atopic dermatitis (AD) taking dupilumab experienced less severe COVID-19 symptoms and overall reduced incidence of infection when compared with patients on other systemic treatments or limited to no treatment.1
“This study is important in this era where we want to ensure that we are treating our patients with moderate to severe disease with medications that do not increase their risk to more severe COVID responses in the case of an infection and perhaps even can attenuate this risk. The findings that dupilumab, and likely other specific [T helper (TH) 2 cytokine] targeting agents, may attenuate responses in case of COVID infections has important implications for treatment choices in our moderate to severe patients with AD,” commented Emma Guttman-Yassky, MD, PhD, corresponding author of the study and Waldman Professor and System Chair of Dermatology and Immunology at the Icahn School of Medicine at Mount Sinai in New York City, NY.
To share further insights on the study, lead author Benjamin Ungar, MD, met with The Dermatologist in this exclusive interview to discuss the study, titled “COVID-19 Symptoms Are Attenuated in Moderate-to-Severe Atopic Dermatitis Patients Treated with Dupilumab.”1
Dr Ungar is an assistant professor of dermatology and director of the Rosacea & Seborrheic Dermatitis Clinic at Mount Sinai. In addition to rosacea and seborrheic dermatitis, Dr Ungar specializes in medical research that clinically focuses on AD, including vascular inflammation, type 2 immune responses, and more.
What was the reason you and your team conducted this study?
At the beginning of the pandemic, there were many, many questions in every facet regarding COVID-19. In the inflammatory skin space, biologics and immunomodulatory medications are extremely common. Thus, one of the first questions that every patient wanted to know was, “Should I continue my biologic therapies?” Part of the goal of the study was to be able to answer that question with data, not just based on past experiences.
In parallel, Dr Guttman-Yassky made an important clinical observation. She had a number of patients with moderate to severe AD being treated with dupilumab who became infected with SARS-CoV-2 but seemed to have more mild symptoms of disease. However, people in their family—partners, parents, children—had very severe manifestations of COVID-19. That observation prompted the question: is there something going on with dupilumab that was affecting COVID-19 symptom experiences for the better? With those two points in mind, we launched this huge effort to answer those questions.
What research or evidence led your group to hypothesize that TH2 targeting with the IL-4Rα antagonist, dupilumab, could rebalance the TH1/TH2 immune axis?
It was a combination of a couple different factors. First, we observed that dupilumab seemed to have a potentially protective, and certainly not worsening, effect on COVID-19. Because we know the effects of the treatment, we wanted to better understand the mechanism by which those effects manifest.
Along with that observation, it has been hypothesized for a long time that the different axes of the immune system—in this case, focusing on TH1 and TH2—may be counterregulatory, or affect the expressions of each one separately. In this study, we are referring to the idea that elevated TH2 inflammation may inhibit TH1 upregulation in the setting of infection. There is also evidence for this interaction in some other respiratory viral infections, to some extent or another where people with elevated TH2 may not mount as robust of a TH1 response, may experience more severe symptoms, and so on.
Putting those factors together, the hypothesis was that dupilumab, by blocking or modulating TH2 signaling, would allow that TH1 response that we want in the setting of a viral infection such as COVID-19.
What is known about the impact of COVID-19 on patients with moderate to severe AD taking the biologic dupilumab?
Since the start of the pandemic, there have been several case reports and case series that suggested that dupilumab treatment in the setting of moderate to severe AD did not seem to have a huge impact on people getting very sick with COVID-19.2-6 However, we cannot draw strong conclusions from that evidence because there is no comparison and the sample of patients is small.
Our recently published paper1 included more than 1200 patients with AD. Some of these patients were on dupilumab, whereas some received more broad-acting systemic therapies and others were not being treated with systemic therapies. Using these patient data, we were able to compare the effects of the different treatments on COVID-19 symptoms and outcomes.
The study showed that dupilumab appears to be protective in terms of leading to more severe COVID-19 symptoms. It reduces the symptom severity. There are some other studies that have been published that hint at that as well,7,8 but our study is really the first one with a more rigorous base for the conclusions to be drawn.
Can you share what areas of future research are needed to better understand COVID-19 immune responses and symptoms in patients with moderate to severe AD?
This is an ongoing effort in a lot of different ways, because we know from this study that COVID-19 symptoms are reduced in patients on a therapy that inhibits IL-4 activity. We still have many questions: What are the long-term effects of all of this? What happens in the setting of vaccination? Does not being treated with dupilumab help, hurt, or affect vaccine responses? How long will vaccine protection last for? Those are all very important questions, both for physicians and patients.
In parallel, we want to understand the mechanism by which dupilumab influences COVID-19 outcomes. It is one thing to say dupilumab helps reduce symptoms, and from a practical perspective, that is crucial information to know, but we still need to answer how that IL-4Rα inhibition does this. The hope is that we can use this information as a springboard to understand more, even potentially extending beyond AD and COVID-19. The hypothesis that modulating TH2 expression to allow a better TH1 response also potentially applies to other scenarios and other infections as well. There’s still a lot of work to be done.
Are there any tips or insights you would like to share with your dermatology colleagues regarding COVID-19 symptoms in patients with AD?
I think the results of this study really speak for themselves. There are two different aspects I want to highlight. First, dermatologists should not have any hesitation about starting a patient with AD on dupilumab in regard to increased COVID-19 risk. The fact that it appears to reduce symptoms actually suggests that dermatologists may want to consider having an even lower threshold for starting dupilumab, because we know that it is effective in treating the underlying AD. Second, if there is this added benefit of potentially reducing symptom severity—people less sick if they are infected with COVID-19, shorter duration of symptoms, and so on—then we get the benefit of not only treating but also protecting our patients with AD.
References
1. Ungar B, Glickman JW, Golant AK, et al. COVID-19 symptoms are attenuated in moderate-to-severe atopic dermatitis patients treated with dupilumab. J Allergy Clin Immunol Pract. Published online November 1, 2021. doi:10.1016/j.jaip.2021.10.050
2. Ferrucci S, Romagnuolo M, Angileri L, Berti E, Tavecchio S. Safety of dupilumab in severe atopic dermatitis and infection of Covid-19: two case reports. J Eur Acad Dermatol Venereol. 2020;34(7):e303-e304. doi:10.1111/jdv.16527
3. Caroppo F, Biolo G, Belloni Fortina A. SARS-CoV-2 asymptomatic infection in a patient under treatment with dupilumab. J Eur Acad Dermatol Venereol. 2020;34(8):e368. doi:10.1111/jdv.16619
4. Ordóñez-Rubiano MF, Rubiano-Mojica PC, Casas M. Young HIV-positive male patient with severe atopic dermatitis on dupilumab and SARS-CoV-2 infection, a pioneer hypothesis. Int J Dermatol. 2021;60(4):514-515. doi:10.1111/ijd.15499
5. Ceryn J, Niedźwiedź M, Skibińska M, Ciążyńska M, Lesiak A, Narbutt J. COVID-19 in patients with atopic dermatitis treated with dupilumab: three cases and a literature review. Clin Cosmet Investig Dermatol. 2021;14:1131-1138. doi:10.2147/CCID.S321003
6. Stingeni L, Hansel K, Antonelli E, et al. Atopic dermatitis in adolescents: effectiveness and safety of dupilumab in a 16-week real-life experience during the COVID-19 pandemic in Italy. Dermatol Ther. 2021;34(5):e15035. doi:10.1111/dth.15035
7. Wu JJ, Martin A, Liu J, et al. The risk of COVID-19 infection in patients with atopic dermatitis: a retrospective cohort study. J Am Acad Dermatol. Published online October 6, 2021. doi:10.1016/j.jaad.2021.09.061
8. Kridin K, Schonmann Y, Solomon A, et al. Risk of COVID-19 and its complications in patients with atopic dermatitis undergoing dupilumab treatment-a population-based cohort study. Immunol Res. Published online October 13, 2021. doi:10.1007/s12026-021-09234-z
