“Dupixent (ingredient: dupilumab) inhibits the Th2 pathway, which is involved in the Covid-19 cytokine storm. But it does not affect the Th1 pathway required to fight the infection. A majority of atopic dermatitis (AD) patients who were using Dupixent were asymptomatic or had mild symptoms even when they were infected with Covid-19, while many others using immunosuppressants such as cyclosporine had to be hospitalized after the infection.”

Emma Guttman, the co-founder of the International Eczema Council and specialist at the Dermatology and Immunology Department of the Icahn School of Medicine at Mount Sinai Medical Center, said this and other remarks on how to treat AD during the Covid-19 pandemic in a recent interview.

Guttman is a world-renowned expert who discovered the “type 2 inflammation” in the immunological bases of AD, proposed new treatment methods, and opened a new chapter in AD treatment.

Korea Biomedical Review conducted a video interview with Guttman to learn the latest knowledge about AD treatment and her know-how coming from treating AD patients during Covid-19.

​Emma Guttman, a professor of dermatology and immunology at the Icahn School of Medicine at Mount Sinai Medical Center​
​Emma Guttman, a professor of dermatology and immunology at the Icahn School of Medicine at Mount Sinai Medical Center​

Question: After researchers found that “type 2 inflammation” was the leading cause of AD, Korean patients and doctors pay more attention to this. What is type 2 inflammation?

Answer: Type 2 inflammation is caused by an increase in cytokines such as interleukin 4 (IL-4) and interleukin 13 (IL-13), and these two cytokines are mostly found in patients with genetic factors. When T lymphocyte cells produce too many IL-4 and IL-13, it can cause a problem. This overproduction causes allergic diseases such as AD, asthma, allergic rhinitis, and chronic rhinosinusitis. These are typical immune-mediated diseases caused by type 2 inflammation.

Q: You are one of the first researchers who applied the type 2 inflammatory mechanism to AD treatment. How did you start your research?

A: I have AD. One of my children has AD, and the other has asthma. So, I couldn’t help but pay more attention to the mechanism of pathogenesis of AD. When I started my research, little was known about the pathogenesis. There was no clear conclusion about whether the AD was caused by a problem in the skin barrier or the immune system. I only know that AD continued to appear in patients related to type 2 inflammation. So, I could naturally come up with a hypothesis that targeting cytokines that induce type 2 inflammation could affect treatment outcomes.

Q: Does type 2 inflammation cause all AD?

A: Most patients with AD have a type 2 inflammatory response. Of course, it is a very complex disease, and other factors can also affect it. But, even taking this into account, the type 2 inflammatory mechanism is almost always an “essential condition.” Reducing the type 2 inflammatory response reverses the problems of skin barrier function. In other words, type 2 inflammation is the leading cause of AD.

Q: Are the latest AD treatments such as Dupixent based on the type 2 inflammation research?

A: Yes. Existing AD treatments include cyclosporine, methotrexate, and oral steroids. These drugs have a broad scope of efficacy. Because they target various immune substances in addition to type 2 inflammation, their safety concerns may appear more broadly. As people had a better understanding of type 2 inflammatory mechanism in AD, researchers thought that selective targeting of Th2 cells could lead to effective treatment. Accordingly, biological agents, such as Dupixent, were developed. With Dupixent available, physicians can use it as an alternative treatment option in AD, but asthma, eosinophilic esophagitis, and chronic rhinosinusitis with nasal polyps caused by type 2 inflammation.

Q: You mentioned earlier that type 2 inflammation is highly associated with genetic factors. If so, does the onset of AD appear differently depending on race?

A: AD is highly prevalent in Asia. A Chinese study found that 10 percent of the adult population and 20 percent of children developed AD. Even in the U.S., the proportion of patients with severe AD is also high among Asians living in the U.S. I provide patient care in New York, and many of them are Asians. In contrast, Asians’ psoriasis prevalence is lower than that of AD.

Q: The Covid-19 pandemic has raised more concern about AD treatment because it is one of the immune-mediated diseases. What’s your opinion on this?

A: New York has been hit particularly hard by Covid-19. I could see many AD patients who were infected with Covid-19. So, the pandemic makes it more challenging to choose a drug for AD treatment.

Recently, the Mount Sinai Hospital in New York conducted a registry-based study. The study aimed to analyze the effects of various AD treatments on patients with moderate to severe AD who need to undergo systemic therapy in the Covid-19 situation.

During the study, we heard a story about Covid-19-related cytokine storm. We realized that Th2 cytokines such as IL-4, IL-5, and IL-13 were related to Covid-19 cytokine storm. Thus, we established a hypothesis that a therapeutic agent targeting Th2 cells could help treat Covid-19.

Dupixent inhibits the Th2 pathway involved in the cytokine storm but does not affect the Th1 path needed to fight infection, and I thought this could be a significant point.

Indeed, most of the Dupixent-treated patients among about 1,500 AD patients we registered were either asymptomatic or had mild symptoms when infected with Covid-19.

In contrast, those who used immunosuppressants such as cyclosporine suffered worsening conditions due to Covid-19 infection, and many of them had to be hospitalized. We could conclude that a therapeutic agent targeting Th2 was a safer approach in the current Covid-19 situation.

Q: We heard that you were participating in various AD studies. What is the outlook of the AD treatment environment, and what tips can you share based on your studies?

A: I am very interested in the accurate diagnosis of AD. It isn't easy to perform a biopsy on infants and toddlers, so I wondered if any method could be as non-invasive as possible. To address this issue, I started a study on NOS2, a biomarker, using a “tape strip.” The study aims to distinguish between AD and psoriasis using a single gene biomarker associated with NOS2. A NOS2 value could be considerably high in psoriasis patients, while that of AD patients could be low. So, this is an excellent biomarker candidate. If such a test method becomes available, we could distinguish AD and psoriasis in patients where the two are difficult to identify with the naked eye.

Also, the AD Quality of Care (QoC) study was meaningful because we could confirm the successful AD treatment experiences by dermatologists worldwide. For the AD QoC study, we visited AD specializing centers worldwide, including Israel, Europe, and South America. We gathered information after hearing medical staff about the overall process of managing diseases, including the diagnosis and treatment of AD.

We collected various information, such as how the actual treatment works, how patients participate in treatment, and what kinds of disease education are available for patients. During the AD QoC study, we could gain new perspectives and approaches from various AD treatment centers.

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