Patients with chronic spontaneous urticaria (CSA) who has uncontrolled disease despite treatment with H1-antihistamines may benefit from using dupilumab, which has been shown to reduce itch and urticaria activity in two phase III trials.

“CSU can be difficult to manage, with inadequate disease control in many patients despite H1-antihistamine treatment,” said lead author Dr Thomas Casale, Division of Allergy and Immunology, Department of Medicine, University of South Florida, Tampa, Florida, US.

Casale presented the findings from LIBERTY-CSU CUPID Study A and Study C at the 2025 AAAAI/WAO Joint Congress. He and his team conducted the replicate, 24-week, randomized, placebo-controlled, double-blind, phase III trials of dupilumab treatment in omalizumab-naive patients with symptomatic CSU (aged ≥6 years) despite standard-of-care H1-antihistamine treatment (A: n=138; C: n=151).

Eligible patients were randomly allocated to receive add-on dupilumab (pooled: 144 patients) 300 mg (adults, adolescents: ≥60 kg) or 200 mg (adolescents: <60 kg; children: ≥30 kg) or matching placebo (pooled: 145 patients) subcutaneously every 2 weeks.

To assess efficacy, the researchers measured the Itch Severity Score over 7 days (ISS7; range, 0?21) and Urticaria Activity Score over 7 days (UAS7; range, 0?42). They also assessed the safety and tolerability of dupilumab in CSU patients.

Compared with placebo, dupilumab use resulted in significant improvements in ISS7 and UAS7 at week 24 in the pooled dataset. Least squares mean change from baseline was ?9.9 with dupilumab versus ?6.7 with placebo (difference, ?3.2; nominal p<0.0001) for ISS7 and ?19.3 versus ?13.1, respectively (difference, ?6.2; nominal p<0.0001), for UAS7. [AAAAI/WAO 2025, abstract L02]

At week 24, significantly more patients treated with dupilumab than placebo achieved well-controlled disease status (UAS7 ≤6: 43.1 percent vs 23.4 percent; odds ratio [OR], 3.0; nominal p<0.0001) or complete response (UAS7=0: 30.6 percent vs 15.9 percent; OR, 2.8; nominal p<0.001).

The incidence of treatment-emergent adverse events did not significantly differ between the two groups (53.5 percent vs 55.9 percent). In addition, the safety profile of dupilumab was generally consistent with previous reports.

LIBERTY-CSU-CUPID

In an article published by the Journal of Allergy and Clinical Immunology, findings from LIBERTY-CSU CUPID Study A and Study B showed clinically significant improvements in urticaria disease activity with dupilumab. Reductions were observed in itch and hive severity among omalizumab-naive patients with CSU who remain symptomatic despite H1-antihistamine use. [J Allergy Clin Immunol 2024;154:184-194]

Those who were intolerant of or incomplete responders to omalizumab also achieved slight improvements in urticaria activity score, including in itch and hives severity, following dupilumab use.

“These findings are particularly important given the lack of approved treatment options for patients with CSU who do not respond to high-dose H1-antihistamine and anti-IgE treatment,” according to the researchers. “Dupilumab reduced urticaria disease activity driven by improvements in itch and hive severity in patients with CSU uncontrolled with standard of care.”

CSU, a chronic inflammatory disease, is characterized by recurrent pruritic wheals (hives) and angioedema for 6 weeks or more with no known trigger. [Handb Exp Pharmacol 2022;268:117-133]