Dupilumab Reduces Urticaria Activity in Anti-IgE–Naive Patients with CSU

Dupilumab significantly reduces urticaria activity by lowering chronic spontaneous urticaria (CSU) symptom severity in anti-IgE–naive individuals who remained symptomatic despite using histamine 1–receptor antagonists (H1-AH; antihistamines).1

These findings, resulting from the CUPID-C randomized clinical trial, confirmed previous findings from CUPID-A.2 Thomas B. Casale, MD, of the Division of Allergy and Immunology at the University of South Florida, Tampa Department of Medicine, authored these data alongside a team of other investigators.

Casale and coauthors set out to “further evaluate the efficacy and safety of dupilumab vs placebo in anti-IgE–naive patients with CSU uncontrolled by H1-AH.”1

CUPID-C Trial Design

The investigative team determined participants eligible to be involved would be between 6 - 80 years of age and have a CSU diagnosis at least 6 months prior to screening. All had reported persistent itch and hives for more than 6 consecutive weeks despite treatment with H1-AH during this interval. Patients were required to be on a protocol-specified H1-AH regimen for CSU with a stable dose for 3 consecutive days before screening at minimum, allowing doses up to 4 times the recommended amount, or up to twice the recommended dose in Japan. None had previously been treated with omalizumab therapy.

The CUPID-C analysis was designed to replicate the earlier LIBERTY-CSU CUPID-A trial. It lasted 24 weeks and used a phase 3, multicenter, randomized, double-blind, placebo-controlled study design. Casale et al assessed dupilumab utilization in anti-IgE–naive individuals with CSU who continued to have symptoms despite H1-AH use. It was conducted across 9 countries: Argentina, China, Canada, France, Hungary, Germany, Japan, the US, and Spain.

The primary efficacy endpoint in CUPID-C, as well as in pooled analyses of CUPID-A and CUPID-C, was the change from baseline to week 24 in either the 7-day Itch Severity Score (ISS7) or the 7-day Urticaria Activity Score (UAS7), with the alternate measure designated as a key secondary endpoint according to regional regulatory guidance. Statistical analyses were carried out between August and September 2024.

In CUPID-C, the investigative team involved 151 participants, with a mean age of 44.7 years and 70.2% being female. At the point of baseline, 51% were on H1-AH at doses exceeding the recommended level. Additionally, the team found 59.6% had a UAS7 score of 28 or higher. By the 24-week mark, dupilumab use was linked with significantly greater reductions in both ISS7 and UAS7 compared with placebo. The least squares mean (SE) shift in ISS7 was −8.64 (1.41) with dupilumab as opposed to −6.10 (1.40) with placebo.

This corresponded with a between-group difference of −2.54 points (95% CI, −4.65 to −0.43; P = .02). For UAS7, Casale and coauthors found the least squares mean (SE) change was −15.86 (2.66) among those in the dupilumab arm of the study, compared with −11.21 (2.65) in the placebo arm, yielding a difference of −4.65 points (95% CI, −8.65 to −0.65; P = .02). When Casale and colleagues pooled the data from CUPID-A and CUPID-C, encompassing 289 patients, improvements in both UAS7 and ISS7 were shown to be greater with dupilumab than with placebo.

In their safety findings, the results were found to have aligned with the established safety profile of dupilumab. In the investigators’ combined analysis, treatment-emergent adverse events (TEAEs) were reported in 53.5% of the subjects on dupilumab and 55.9% of those on placebo. Overall, the CUPID-C randomized study corroborated the results of CUPID-A, with the pooled findings suggesting dupilumab significantly diminished overall urticaria activity by lessening both itch intensity and hive severity in these individuals.

“These results are consistent with the findings from the previous replicate study, CUPID-A,” Casale and colleagues wrote.1,2 “The combined data from CUPID-A and -C collectively reinforce the clinical benefits and safety profile of dupilumab for H1-AH−refractory and omalizumab-naive patients with CSU.”

References

1. Casale TB, Saini SS, Ben-Shoshan M, et al. Dupilumab in Patients With Chronic Spontaneous Urticaria: Phase 3 LIBERTY-CSU CUPID Randomized Clinical Trials. JAMA Dermatol. Published online February 18, 2026. doi:10.1001/jamadermatol.2025.6023.

2. Maurer M, Casale TB, Saini SS, et al. Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): two randomized, double-blind, placebo-controlled, phase 3 trials. J Allergy Clin Immunol. 2024;154(1):184-194. doi:10.1016/j.jaci.2024.01.028.