Thomas Casale, MD, on the Efficacy of Dupilumab for Chronic Spontaneous Urticaria

Dr Casale provides an overview of his poster presentation at the American Academy of Allergy, Asthma, and Immunology annual meeting on whether age, gender, BMI, presence of angioedema, or IgE level affected how patients with chronic spontaneous urticaria responded to treatment with dupilumab.

Thomas B. Casale, MD, is professor of Medicine and Pediatrics and chief of Clinical and Translational Research at University of South Florida Division of Allergy and Immunology in Tampa, Florida.

Dupilumab Demonstrates Consistent Efficacy Across Patient Subgroups in Chronic Spontaneous Urticaria (CUPID A and C Studies)

• Chronic spontaneous urticaria (CSU); dupilumab (IL-4/IL-13 inhibitor targeting the IL-4α receptor) Analyses of patients enrolled in the pivotal CUPID A and CUPID C studies, recently published in JAMA Dermatology and presented at the American Academy of Allergy, Asthma & Immunology meeting, showed that dupilumab significantly improved disease activity and itch in CSU, measured by Urticaria Activity Score 7 (UAS7) and Itch Severity Score 7 (ISS7), supporting its role as a new treatment option alongside earlier therapy omalizumab (anti-IgE monoclonal antibody, approved 2013) and newer therapy remibrutinib (BTK inhibitor).

• Subgroup analysis—age, sex, BMI, and angioedema: Patients <65 vs ≥65 years, male vs female, BMI <25, 25–30, or >30, and those with or without angioedema demonstrated similar clinical improvements with dupilumab, indicating that treatment response was consistent across demographic and disease-severity subgroups, including patients with angioedema who often have more severe CSU.

• IgE stratification analysis and dosing: Unlike prior observations with omalizumab, where low IgE levels may reduce or delay response, dupilumab showed comparable efficacy versus placebo across low, intermediate, and high IgE levels. The therapy is administered as a subcutaneous injection every 2 weeks, providing a treatment option for CSU patients whose disease significantly impairs quality of life.

TRANSCRIPT:

Hi, my name is Dr. Tom Casale. I am an allergist and immunology professor of medicine at the University of South Florida in Tampa. And at the recent American Academy of Allergy, Asthma, and Immunology meeting, we presented a couple of abstracts centered on dupilumab and its effects in chronic spontaneous urticaria. As you're aware, CSU is a very debilitating disease for a lot of people. It impairs quality of life significantly and often impairs people in their ability to enjoy outside activities because of the embarrassment of the lesions, et cetera. So it's important that we get newer therapies.

Omalizumab, the anti-IgE monoclonal antibody, was approved in 2013 for CSU, but over the last few months, we've had 2 new approvals for CSU. One is remibrutinib, which is a BTK inhibitor, and the second was dupilumab, which we're going to discuss today. Dupilumab is an interleukin-4/13 inhibitor. It blocks the IL-4 alpha receptor, which is the common receptor for both 4 and 13. And because of the role of 4 and 13 in CSU, it made a lot of sense to look at its effects in chronic spontaneous urticaria.

So what we reported are data from patients that were enrolled in the pivotal studies for chronic spontaneous urticaria, and these studies are labeled CUPID A and CUPID C. And the results of the combined dataset for A and C have recently been published in JAMA Dermatology, but in these 2 abstracts I'd like to briefly discuss, we look at subpopulations.

So overall, we know that dupilumab works in CSU, and that's why the FDA approved it, but there are some questions, and some of those questions center around earlier data from omalizumab in that patients that have certain characteristics either respond more slowly or less vigorously than other patients. And those patients in particular were noted to have high BMIs and very low IgE levels. So in these two studies that we're going to look at, we examined patient responses to dupilumab regardless of what their age, gender, BMI, or presence of angioedema was. And then in a second abstract that was presented, we looked at the responses based on IgE levels.

So in the first one, we found that patients that were broken up either into less than 65 years of age and greater than 65 years of age, or male or female, they responded equally well to dupilumab with improvements in the Itch Severity Score (ISS7)  or the Urticaria Activity Score 7. We also looked at the presence of angioedema, because we know that in patients that have angioedema with their CSU, they tend to have a more serious disease that sometimes is harder to treat. And again, we found no difference in the responsiveness whether they did or did not have angioedema.

And then we finally, we looked at BMI. So we broke up the group into 3 different BMI categories, and those include a BMI less than 25, 25 to 30, and greater than 30. And we found that patients were equally responsive to dupilumab regardless of what their BMI was.

So then we also looked at IgE levels, because as I indicated, there are some data to suggest that patients on omalizumab may not respond quite as quickly or quite as well if their IgE levels are low. So in a second abstract, we looked at that and we found that regardless of how we cut the data for the IgE levels, patients responded equally well on dupilumab versus placebo, whether they had low, intermediate, or high levels of IgE. So overall, the data suggests that patients with CSU can be effectively treated with dupilumab, which is a subcutaneous injection every 2 weeks, regardless of their age, their gender, the BMI, presence of angioedema, or IgE level.

So this provides another good therapeutic options for the patients that have this severe disease in some cases that really impairs quality of life. Thank you.