Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): Two randomized, double-blind, placebo-controlled, phase 3 trials

Marcus Maurer; Thomas B Casale; Sarbjit S Saini; Moshe Ben-Shoshan; Ana M Giménez-Arnau; Jonathan A Bernstein; Akiko Yagami; Aleksandra Stjepanovic; Allen Radin; Heribert W Staudinger; Naimish Patel; Nikhil Amin; Bolanle Akinlade; Chunpeng Fan; Deborah Bauer; George D Yancopoulos; Kiran Patel; Leda P Mannent; Elizabeth Laws

doi:10.1016/j.jaci.2024.01.028

Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): Two randomized, double-blind, placebo-controlled, phase 3 trials

J Allergy Clin Immunol. 2024 Feb 29:S0091-6749(24)00196-9. doi: 10.1016/j.jaci.2024.01.028. Online ahead of print.

Authors

Marcus Maurer¹, Thomas B Casale², Sarbjit S Saini³, Moshe Ben-Shoshan⁴, Ana M Giménez-Arnau⁵, Jonathan A Bernstein⁶, Akiko Yagami⁷, Aleksandra Stjepanovic⁸, Allen Radin⁹, Heribert W Staudinger¹⁰, Naimish Patel¹⁰, Nikhil Amin⁹, Bolanle Akinlade⁹, Chunpeng Fan¹¹, Deborah Bauer¹¹, George D Yancopoulos⁹, Kiran Patel¹⁰, Leda P Mannent⁸, Elizabeth Laws¹¹

Affiliations

¹ Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität, Berlin, and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany. Electronic address: marcus.maurer@charite.de.
² Division of Allergy and Immunology, Department of Medicine, University of South Florida, Tampa, Fla.
³ Johns Hopkins Asthma and Allergy Center, Baltimore, Md.
⁴ Division of Allergy, Immunology, and Dermatology, Department of Pediatrics, McGill University Health Centre, Montreal, Quebec, Canada.
⁵ Department of Dermatology, Hospital del Mar, Institut Mar D'Investigacions Mediques, Universitat Autónoma y Universitat Pompeu Fabra, Barcelona, Spain.
⁶ Division of Allergy and Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, Partner Bernstein Allergy Group and Bernstein Clinical Research Center, Cincinnati, Ohio.
⁷ Department of Allergology, Fujita Health University School of Medicine, Aichi, Japan.
⁸ Sanofi, Chilly-Mazarin, France.
⁹ Regeneron Pharmaceuticals Inc, Tarrytown, NY.
¹⁰ Sanofi, Cambridge, Mass.
¹¹ Sanofi, Bridgewater, NJ.

PMID: 38431226
DOI: 10.1016/j.jaci.2024.01.028

Abstract

Background: Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by recurrent pruritic wheals (hives) and/or angioedema. Patients with CSU could remain symptomatic despite standard-of-care H₁ antihistamines (H1-AH) or anti-IgE (omalizumab) treatment. Dupilumab blocks IL-4/IL-13 signaling and is approved for multiple type 2/atopic indications.

Objective: We conducted two phase 3, randomized, placebo-controlled, double-blind trials comparing dupilumab with placebo in patients with symptomatic CSU despite H1-AH.

Methods: In LIBERTY-CSU CUPID Study A, patients were omalizumab-naive (n = 138, aged ≥6 years). In Study B, patients were omalizumab-intolerant/incomplete responders (n = 108, aged ≥12 years). The primary end point was either change from baseline over 7 days in the Urticaria Activity Score (UAS7) or Itch Severity Score (ISS7) at week 24, with the other as a key secondary end point, depending on regional regulatory requirements. Studies were pooled for safety assessment.

Results: In Study A, UAS7 and ISS7 improved with dupilumab versus placebo (difference -8.5 [95% CI, -13.2 to -3.9; P = .0003] and -4.2 [95% CI, -6.6 to -1.8; P = .0005]). In Study B, tested at α = 0.043 after interim analysis, UAS7 improved (difference -5.8 [95% CI, -11.4 to -0.3; P = .0390]), with a numerical trend in ISS7 (difference -2.9 [95% CI, -5.7 to -0.07; nominal P = .0449, not significant]). Pooled safety data were consistent between dupilumab and placebo and with the known dupilumab safety profile.

Conclusions: Dupilumab reduced urticaria activity by reducing itch and hives severity in omalizumab-naive patients with CSU uncontrolled with H1-AH. Although the primary end point for Study B was not met, dupilumab effects were small in patients who were omalizumab-intolerant/incomplete responders.

Keywords: Chronic spontaneous urticaria; H(1) antihistamines; dupilumab; intolerant/incomplete responders; omalizumab; uncontrolled; urticaria activity.