LIBERTY-CSU CUPID-C: Improved Itch in Spontaneous Chronic Urticaria with Dupliumab

Key Takeaways

• Data from the LIBERTY-CSU CUPID-C  trial suggests dupilumab improved itch and hives severity at 24 weeks in anti-IgE–naive patients with chronic spontaneous urticaria (CSU) uncontrolled by H1-antihistamines.

• Pooled CUPID-A and CUPID-C data (N = 289) showed improvements in urticaria activity as early as week 3, as well as higher rates of well-controlled and completely controlled disease.

• Safety was comparable to previous dupilumab studies. 

Dupilumab significantly reduced itch and hives severity in patients with chronic spontaneous urticaria (CSU) who remained symptomatic despite histamine 1–receptor antagonist (H1-AH) therapy, according to results from the phase 3 LIBERTY-CSU CUPID-C trial published in JAMA Dermatology.

LIBERTY-CSU CUPID-A (2019-2021) was a previous phase 3 randomized controlled trial showing dupilumab significantly reducing itch and hive severity in anti−immunoglobulin E (IgE)−naive patients with CSU uncontrolled with H1-AH. As a replicative trial required by the FDA, CUPID-C was a 24-week, randomized, double-blind, placebo-controlled trial conducted across nine countries between 2022 and 2024. The study included 151 anti-immunoglobulin E (IgE)–naive patients aged 6 to 80 years with CSU inadequately controlled on stable H1-AH doses. More than half (59.6%) of included patients had severe disease (UAS7 ≥28) at baseline. Participants were randomized 1:1 to dupilumab or placebo plus background antihistamines.

At week 24, dupilumab-treated patients saw greater reductions in Itch Severity Score over 7 days (ISS7) vs. placebo (least squares mean change −8.64 vs −6.10; difference −2.54 [95% CI, −4.65 to −0.43]; P = 0.02). Urticaria Activity Score also improved over 7 days (UAS7) (−15.86 vs −11.21; difference −4.65 [95% CI, −8.65 to −0.65]; P = 0.02) and Hives Severity Score over 7 days (HSS7) (P = 0.03).

Pooled analyses of CUPID-A and CUPID-C (N = 289) showed dupilumab associated with larger reductions in ISS7 (−9.94 vs −6.71; nominal P < 0.001) and UAS7 (−19.29 vs −13.13; nominal P < 0.001), with separation from placebo beginning at week 3. At week 24, 43.1% of dupilumab-treated patients achieved well-controlled disease (UAS7 ≤6) vs. 23.4% with placebo; 30.6% vs. 15.9% achieved complete response (UAS7 = 0).

Treatment-emergent adverse events occurred in 53.5% of dupilumab-treated patients and 55.9% of placebo recipients in pooled analyses. Serious adverse events were infrequent.

“Dupilumab demonstrated significant and clinically meaningful efficacy in omalizumab-naive patients with CSU who remained symptomatic despite H1-AH treatment in CUPID-C,” the authors wrote. “The combined data from CUPID-A and -C collectively reinforce the clinical benefits and safety profile of dupilumab for H1-AH–refractory and omalizumab-naive patients with CSU.”

Source: Casale T, et al. JAMA Dermatology. doi:10.1001/jamadermatol.2025.6023