Beyond Antihistamines: Dupilumab for Chronic Urticaria

Original Article : Dupilumab in Patients With Chronic Spontaneous Urticaria

Phase 3 LIBERTY-CSU CUPID Randomized Clinical Trials

What are the key takeaways of this article?

Chronic spontaneous urticaria (CSU) is a condition characterized by recurrent hives, angioedema, and intense itching that persist for more than 6 weeks without a clear trigger. Despite treatment with antihistamines, many patients continue to experience persistent symptoms, significantly impairing sleep, daily functioning, and overall quality of life.

Emerging research highlights the role of type 2 inflammation in CSU pathogenesis. Key immune pathways that involve interleukin-4 (IL-4) and interleukin-13 (IL-13) contribute to mast cell activation and increased itch sensitivity. Dupilumab is a biologic therapy that blocks IL-4 and IL-13 signaling, targeting this underlying inflammatory pathway to relieve CSU symptoms.

The phase 3 LIBERTY-CSU CUPID clinical program evaluated dupilumab in patients with CSU who remained symptomatic despite antihistamine treatment and had not previously received anti-immunoglobulin E (IgE) therapy. The CUPID-C trial (2022-2024) was a randomized, double-blind, placebo-controlled study that replicated the earlier CUPID-A trial. A total of151 patients were included in CUPID-C, with pooled analyses from both trials including 289 patients. Participants received dupilumab or placebo for 24 weeks while continuing background antihistamines.

By week 24, dupilumab significantly improved both itch severity and hive activity compared to placebo. Patients treated with dupilumab had greater reductions in itch severity scores over 7 days (ISS7) and overall urticaria activity scores over 7 days (UAS7). Importantly, improvements were seen early, with symptom relief beginning as soon as week 3. A higher proportion of patients achieved well-controlled or completely controlled disease with dupilumab compared to placebo.

Dupilumab also reduced serum IgE levels and showed consistent efficacy regardless of baseline IgE levels or the presence of angioedema. This suggests that targeting IL-4/IL-13 pathways may benefit a broad spectrum  of CSU patients, including those who may respond inadequately to anti-IgE therapies such as omalizumab.

In terms of safety, dupilumab was generally well tolerated, with similar rates of treatment-emergent adverse events compared to placebo (53.5% vs 55.9%). Most side effects were mild, and no new safety concerns were identified. Serious adverse events were uncommon and occurred at similar rates between groups.

Overall, this study reinforces that CSU is a biologically driven inflammatory disease rather than solely a histamine-mediated condition. By targeting upstream immune pathways, dupilumab offers a mechanism-based treatment option for patients with persistent symptoms despite standard therapy. These findings expand the treatment landscape for CSU and support a shift toward more targeted, pathway-driven management.

Publication Date: August 3, 2026

Reference:

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. 2026;162(4):350–358. doi:10.1001/jamadermatol.2025.6023

Summary By: Nicole Chu