Treating Chronic Spontaneous Urticaria: Findings from the LIBERTY-CSU CUPID Study A

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The 2024 Fall Clinical Dermatology Conference for PAs and NPs in Scottsdale, Arizona, featured a poster presentation on the efficacy of dupilumab in treating chronic spontaneous urticaria (CSU). This poster detailed the findings from the LIBERTY-CSU CUPID Study A, a randomized controlled trial evaluating the use of dupilumab in CSU patients refractory to H1-antihistamines (H1-AH).¹

Background

Chronic spontaneous urticaria (CSU) is a persistent condition characterized by recurrent wheals and/or angioedema for over 6 weeks. While the majority of CSU cases resolve spontaneously within 2 to 5 years, approximately 20% of patients experience symptoms for more than 5 years, with some enduring multiple episodes throughout their lifetime. Standard treatments often fail to provide adequate relief, necessitating the exploration of alternative therapies. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, thereby inhibiting IL-4 and IL-13 signaling, is under investigation as a potential treatment for these patients.

Endpoints and Results

The LIBERTY-CSU CUPID Study A included patients aged 6 years and older, diagnosed with CSU for over six months, and symptomatic despite standard H1-AH treatment. Participants were omalizumab-naive and excluded if they had active atopic dermatitis. The study employed a double-blind, placebo-controlled design, with patients randomized to receive either dupilumab or a placebo.

Key efficacy endpoints included the proportion of patients achieving a Urticaria Activity Score over 7 days (UAS7) of ≤6 (well-controlled urticaria) and 0 (urticaria-free) from week 1 to week 36. Safety outcomes assessed treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). 

The study enrolled 138 patients (70 dupilumab, 68 placebo). Demographics and baseline characteristics were comparable across groups:

• Mean age: 41.3 years
• Female: 65.9%
• Mean baseline UAS7: 31.3
• Mean baseline ISS7: 15.9

Dupilumab demonstrated significant efficacy in reducing CSU disease activity compared to placebo:

• Well-Controlled Urticaria (UAS7 ≤6):A higher proportion of dupilumab-treated patients achieved well-controlled urticaria from week 8, with a significant difference observed at week 24 (P=0.0379).
• Urticaria-Free Status (UAS7=0):A greater proportion of patients in the dupilumab group achieved urticaria-free status starting from week 14, with a significant difference noted at week 24 (P=0.0411).

These improvements persisted through the 12-week post-treatment follow-up, indicating sustained efficacy even after discontinuation of dupilumab.

The safety profile of dupilumab was consistent with previous studies.TEAEs impacted 54.3% in the dupilumab group versus 58.8% in the placebo group. SAEs were lower in the dupilumab group (2.9%) compared to placebo (7.4%). The most common adverse events included injection-site reactions, which were more frequent in the dupilumab group but generally mild. Notably, no dupilumab-treated patients reported conjunctivitis, a potential concern with this class of medication. 

Clinical Considerations

The LIBERTY-CSU CUPID Study A provided robust evidence supporting dupilumab as an effective and well-tolerated treatment for CSU patients unresponsive to H1-AH therapy. These findings highlight dupilumab's potential to significantly improve disease control and quality of life for patients with this challenging condition. For clinicians managing CSU, these results suggest that dupilumab could be a valuable addition to the therapeutic arsenal, particularly for patients who do not achieve satisfactory control with antihistamines alone. Investigators concluded that as dupilumab continues to demonstrate a favorable safety and efficacy profile, it may become a standardized component for CSU treatment in the near future.²

Related content

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Q&A: Late-Breaking REMIX-1 and REMIX-2 Data Demonstrated Efficacy of Remibrutinib in Chronic Spontaneous Urticaria

References

1. Maurer M, Giménez-Arnau A, Kaplan A, et al. Dupilumab reduces disease activity in patients with chronic spontaneous urticaria: LIBERTY-CSU CUPID Study A. Poster presented at: 2024 Fall Clinical Dermatology Conference for PAs and NPs; May 31-June 2; Scottsdale, AZ.
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. Published online February 29, 2024. doi:10.1016/j.jaci.2024.01.028