Dupilumab in Patients with Chronic Spontaneous Urticaria (LIBERTY-CSU CUPID): Two Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trials.

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 H 1 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, placebocontrolled, 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 a = 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.