Dupilumab (Dupixent) has demonstrated significant efficacy in reducing itch and urticaria in patients with chronic spontaneous urticaria (CSU) whose symptoms are not adequately controlled with H1-antihistamine therapy. The phase III LIBERTY-CUPID study C revealed that dupilumab, when added to standard-of-care H1 antihistamines, led to a statistically significant reduction in itch severity compared to placebo.
Itch and Urticaria Severity Reduction
The study, presented at the American College of Allergy, Asthma & Immunology annual meeting, showed that patients receiving dupilumab experienced an 8.64-point reduction in itch severity from baseline to week 24, compared to a 6.10-point reduction in the placebo group (P = 0.02). Itch severity was measured using the 21-point Itch Severity Score over 7 days (ISS7).
Furthermore, dupilumab treatment resulted in a 15.86-point reduction in urticaria activity (itch and hive) severity from baseline, while the placebo group saw an 11.21-point reduction (P = 0.02). Urticaria activity was assessed using the 42-point Urticaria Activity Score over 7 days (UAS7).
Clinical Significance
According to Dr. Thomas B. Casale, the data at week 24 indicated that nearly twice as many patients on dupilumab achieved a UAS7 score of ≤6 (40.5% with dupilumab vs 23.5% with placebo), signifying well-controlled urticaria. Notably, approximately 30% of patients on dupilumab achieved complete remission (UAS7 score of 0) at 24 weeks, compared to 18% in the placebo group.
Study Design and Patient Population
The LIBERTY-CUPID study C, a placebo-controlled, double-blind, 24-week phase III trial, involved 151 patients aged 6 years or older. Participants were randomized to receive either dupilumab (300 mg for adults and adolescents ≥60 kg, or 200 mg for adolescents <60 kg and children ≥30 kg) or a matching placebo subcutaneously every 2 weeks, in addition to their standard-of-care H1 antihistamines.
The patient demographics were consistent with typical urticaria studies, with a predominantly female population (70%), a median age of approximately 45 years, and a median BMI of 27. The baseline ISS7 score was 15.1, and the baseline UAS7 score was 28.3. Roughly half of the patients were receiving a standard dose of antihistamines, while the other half were on a 2-to-4-fold standard dose.
Safety Profile
The safety profile of dupilumab in this study was consistent with its known safety profile. Treatment-emergent adverse events (TEAEs) were similar in both groups (53%), with nasopharyngitis being the most common (8.1% with dupilumab and 5.2% with placebo). Injection site erythema was observed in 5.4% of patients in the dupilumab group. Severe TEAEs occurred in three patients in the dupilumab group and one in the placebo group, while serious TEAEs occurred in five patients in the dupilumab group and one on placebo.
Regulatory Implications
This study is designed to replicate LIBERTY-CUPID study A, which previously demonstrated dupilumab's efficacy in reducing itch and hive severity in omalizumab-naive patients. Study A supported the approval of dupilumab in Japan for CSU treatment in individuals aged 12 years and older whose condition is not adequately controlled with existing therapies. The results of Study C will support regulatory resubmission in the U.S. following an FDA Complete Response Letter requesting additional efficacy data. If approved, dupilumab would be the first targeted therapy for CSU in a decade, according to Sanofi.
