DUPILUMAB EFFICACY IN PATIENTS WITH CHRONIC SPONTANEOUS URTICARIA BY IGE LEVEL: LIBERTY-CSU CUPID STUDY A

Abstract

<h3>Introduction</h3> Chronic spontaneous urticaria (CSU) causes recurrent itchy hives and/or angioedema, significantly impacting quality of life. Many patients experience a substantial disease burden despite treatment with licensed and escalated doses of H1 antihistamines. <h3>Methods</h3> In LIBERTY-CSU CUPID Study A (NCT04180488), a randomized, placebo-controlled, 24-week, phase 3 trial, patients (≥6 years) with CSU who remained symptomatic despite H1 antihistamine treatment received add-on dupilumab (n=70) (adults/adolescents ≥60kg: 300mg; adolescents <60kg/children ≥30kg: 200 mg) or matching placebo (n=68) subcutaneously every 2 weeks. Endpoints included change from baseline at Week-24 over 7 days in Itch Severity Score (ISS7), Hives Severity Score (HSS7), and Urticaria Activity Score (UAS7). <h3>Results</h3> Baseline characteristics were balanced; mean ISS7 and UAS7 (dupilumab/placebo) were 16.1/15.7 and 31.9/30.8, respectively. At Week-24, least squares (LS) mean change from baseline in ISS7 (range: 0–21) was –10.2/–6.0 (dupilumab/placebo, respectively) (LS mean difference –4.2; <i>P</i>=0.0005) and for UAS7 (range: 0–42) was –20.5/–12.0 (difference –8.5; <i>P</i>=0.0003). Baseline median serum total IgE was 101.0IU/mL (overall population). Dupilumab significantly reduced itch (ISS7), hives (HSS7), and urticaria activity (UAS7) at Week-24 regardless of baseline serum total IgE (<100 /≥100IU/mL): ISS7 LS mean difference vs placebo(95% confidence interval) −4.2(−7.86, −0.62)/−4.6(−8.22, −1.04), respectively; HSS7, −4.2(−7.60, −0.70)/−6.1(−9.95, −2.33); UAS7, –8.2(–15.04, –1.29)/–10.6(–17.72, –3.54). Occurrence of treatment-emergent adverse events (TEAEs) for dupilumab/placebo were 35(50.0%)/40(58.8%); injection-site reactions, 8(11.4%)/9(13.2%); conjunctivitis, 0/1(1.5%); serious TEAEs, 2(2.9%)/5(7.4%). <h3>Conclusion</h3> Dupilumab demonstrated clinically meaningful and statistically significant improvements in patients with H1 antihistamine-resistant CSU regardless of baseline IgE level and was well tolerated.