Itch, urticaria activity improve with dupilumab after refractory antihistamine treatment
Key takeaways:
- Patients remained symptomatic despite H1 antihistamine care and had not tried omalizumab.
- 30.6% of the treatment group and 15.9% of the placebo group achieved complete response.
SAN DIEGO — Patients with chronic spontaneous urticaria that was not controlled with H1 antihistamines experienced improvements in itch and urticaria activity with dupilumab, according to a poster presented here.
These improvements persisted regardless of the patient’s BMI at baseline as well, Thomas B. Casale, MD, chief of clinical and translational research, division of allergy and immunology, University of South Florida, told Healio during the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
“Dupilumab affects the IL-4-alpha receptor, which is a receptor that’s important for both IL-4 and IL-13 signaling, and those two cytokines are very important for T2-driven inflammation, which we know happens in most patients with urticaria,” Casale told Healio.
The study included patients with chronic spontaneous urticaria (CSU) aged 6 to 80 years who had not used omalizumab (Xolair; Genentech, Novartis) with both itch and hives for more than 6 weeks even though they had been using H1 antihistamines.
The 289 patients (mean age, 43.1 years; 68.2% female; 57.1% white) in the cohort also had a 7-day Urticaria Activity Score (UAS7) of 16 or higher and a 7-day Itch Severity Score (ISS7) of at least 7 in the previous 7 days.
“The patient population is very similar to what we see in practice,” Casale said. “They’re all pretty significantly sick.”
Mean baseline UAS7 scores included 29.3 for the placebo group and 30.2 for the dupilumab group. Mean baseline ISS7 scores included 15.4 for the placebo group and 15.7 for the dupilumab group.
At week 24 of treatment with dupilumab (Dupixent; Regeneron, Sanofi), least square mean changes from baseline in ISS7 included –6.7 for the placebo group (n = 145) and –9.9 for the dupilumab group (n = 144), for a –3.2 difference (P < .0001).
Least square mean changes from baseline in UAS7 at week 24 included –13.1 for the placebo group and –19.3 for the dupilumab group, for a –6.2 difference (P < .0001).
Proportions of patients whose disease was well controlled at week 24, defined as a UAS7 score of 6 or lower, included 23.4% of the placebo group and 43.1% of the dupilumab group (P < .0001).
Similarly, proportions of patients who achieved complete response at week 24, defined as a UAS7 score of 0, included 15.9% of the placebo group and 30.6% of the dupilumab group (P = .0009).
There were 81 treatment-emergent adverse events, five severe treatment-emergent adverse events and six treatment-emergent serious adverse events in the placebo group, as well as 77 treatment-emergent adverse events, five severe treatment-emergent adverse events and seven treatment-emergent serious adverse events in the dupilumab group.
The single treatment-emergent adverse event leading to death in the study occurred in the placebo group. Also, the placebo group had five treatment-emergent adverse events leading to permanent study intervention discontinuation, and the dupilumab group had two.
The most common treatment-emergent adverse events reported by 5% or more of patients in either group included nasopharyngitis, with eight in the placebo group and five in the dupilumab group, and CSU, with nine in the placebo group and five in the dupilumab group.
Also, the researchers stratified outcomes among 68 patients in the placebo group and 70 patients in the dupilumab group based on baseline BMI.
“The problem we have with urticaria is we don’t have very good biomarkers, so it’s very hard to predict who’s going to respond and not respond,” Casale said.
“That’s what these newer drugs for urticaria have to do. They have to figure out where they fit in the treatment paradigm. You can look at some of the gaps that the existing therapies have, study those, and see whether it makes a difference or not.”
Least square mean changes from baseline to week 24 in ISS7 scores included –4.8 among those on placebo (n = 24) and –10.6 for those on dupilumab (n = 33), with a –5.8 difference between the two, for patients with BMI under 25 kg/m2.
Among patients with BMI between 25 kg/m2 and less than 30 kg/m2, least square mean changes included –6.9 among those on placebo (n = 23) and –9.6 for those on dupilumab (n = 18), with a –2.7 difference between the groups.
Least square mean changes for patients with BMI of 30 kg/m2 and higher included –5.5 of those on placebo (n = 20) and –9 for those on dupilumab (n = 19), with a –3.5 difference between the groups.
Similarly, least square mean changes in UAS7 from baseline to week 24 included –9.3 for those on placebo (n = 24) and –21.3 for those on dupilumab (n = 33), with a –12 difference, among patients with a BMI of less than 25 kg/m2.
Among patients with BMI between 25 kg/m2 and less than 30 kg/m2, least square mean changes included –14.5 for those on placebo (n = 23) and –19.2 for those on dupilumab (n = 18), with a –4.7 difference between the groups.
Least square mean changes for patients with BMI of 30 kg/m2 and higher included –10.5 for those on placebo (n = 20) and –17.5 for those on dupilumab (n = 19), with a –7 difference between the groups.
“In the omalizumab data, if you have high body weight, high BMI, you tend to respond slower, or not quite as well,” Casale said. “So, showing that it doesn’t make any difference [with dupilumab] is important.”
The researchers also are examining whether baseline IgE levels influence the effectiveness of dupilumab in treating CSU, with results to be published later.
“With omalizumab, if you have low IgE, you respond slower, or not as well,” Casale said.
But based on these findings, the researchers concluded itch and urticaria activity both fell with dupilumab for patients whose CSU was uncontrolled with H1-antihistamine treatment, with positive outcomes regardless of their BMI at baseline.
“These data will probably be enough to go to the FDA,” Casale said.
The FDA is scheduled to meet to discuss dupilumab’s approval for CSU on April 18.
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For more information:
Thomas B. Casale, MD, can be reached at tbcasale@usf.edu.