Dupilumab Reduces Itch, Urticaria Activity in Chronic Spontaneous Urticaria

Thomas Casale, MD

Credit: University of South Florida

Pooled results from 2 phase 3 trials showed dupilumab (Dupixent) reduced itch and urticaria activity in patients with chronic spontaneous urticaria who were uncontrolled with H1-antihistamines.¹ The research will be presented at the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) annual meeting in San Diego from February 28 – March 3.

Chronic spontaneous urticaria can be challenging to manage, with many receiving inadequate treatment with H1-antihistamines. Investigators, led by Thomas Casale, MD, from the University of South Florida, examined dupilumab on itch relief and urticaria activity by pooling results from 2 replicate, 24-week, randomized, placebo-controlled phase 3 trials: LIBERTY-CSU CUPID Study A and Study C (NCT04180488).

These trials evaluated dupilumab treatment, a fully human monoclonal antibody that interferes with the signaling of the interleukin-4 and interleukin-13 pathways, in omalizumab-naïve patients aged ≥ 6 years with symptomatic chronic spontaneous urticaria.^1,2 Dupilumab had been improved in > 60 countries for the indications of atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, prurigo nodularis, chronic spontaneous urticaria, and chronic obstructive pulmonary disease.²

In LIBERTY-CSU CUPID Study A and Study C, patients were included if they had chronic spontaneous urticaria despite the standard treatment of H1-anthistimate.¹ In total, 138 patients in study A and 151 patients in study C had a ≤ 4-fold approved dose.

Patients were randomized to receive add-on dupilumab (n = 144), 300 mg for adults and 200 mg for children, or placebo (n = 145) subcutaneously every 2 weeks. Adolescents received either 300 mg or 200 mg of dupilumab.

The primary endpoints were the Itch Severity Score (range: 0 – 21) and the Urticaria Activity Score (range: 0 – 42), both over 7 days. Secondary endpoints included safety and tolerability.

The pooled analysis revealed dupilumab improved itch severity and urticaria activity compared with placebo at week 24. The Itch Severity Score demonstrated patients on dupilumab had least squares mean change from baseline of -9.9, compared with -6.7 on placebo (difference, -3,2; P < .0001). Moreover, patients on dupilumab versus placebo had least squares mean change from baseline in the Urticaria Activity Score of - 19.3 vs -13.1 (difference, - 6.2; P < .0001).

The study showed a greater proportion of patients on dupilumab compared with placebo achieved well-controlled disease status indicated by an Itch Severity Score of ≤ 6: 43.1% vs 23.4% (P < .0001). Additionally, more patients on dupilumab (30.6%) than placebo (15.9%) reached a complete response with an Itch Severity Score of 0 at week 24 (P < .001).

Dupilumab in this pooled analysis had a comparable safety profile to its safety profile seen in other trials. Treatment-emergent adverse events occurred in 53.5% on dupilumab and 55.9% on placebo. Common adverse events seen in study C were injection site reactions, accidental overdose, and COVID-19 infection.

“The positive pivotal data from this study reinforce the potential of Dupixent to offer a new treatment option for the many people suffering from chronic spontaneous urticaria who do not respond to standard-of-care antihistamines,” said Dietmar Berger, MD, PhD, chief medical officer of the Global Head of Development at Sanofi, in a press release for Study C. back in September.2 “With clinically meaningful reductions in itch and hives for patients receiving Dupixent, we look forward to sharing these data with the FDA to bring Dupixent to patients with [chronic spontaneous urticaria] in the US as soon as possible.”

References

1. Casale, T, Saini, S, Bernstein, J, et al. Dupilumab Improves Itch and Urticaria Activity In Patients With Chronic Spontaneous Urticaria: Pooled Results From Two Phase 3 Trials (LIBERTY-CSU CUPID Study A and Study C). Late-breaking abstract presented at AAAAI 2025 in San Diego from February 28 – March 3.

2. Press Release: Dupixent phase 3 study confirms significant improvements in itch and hives for patients with CSU. Sanofi. September 11, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-09-11-05-05-00-2944239. Accessed February 11, 2025.