Dupilumab reduces itch severity and overall disease activity in patients with refractory chronic spontaneous urticaria (CSU), according to the results of a recent trial supporting earlier findings from 2021.
Published in JAMA Dermatology, the phase 3 LIBERTY-CSU CUPID-C trial replicated the earlier CUPID-A study conducted between 2019 and 2021. It assessed the efficacy and safety of the interleukin (IL)-4/IL-13 inhibitor dupilumab versus placebo in patients with CSU inadequately controlled with H1-antihistamines who had not previously received anti-immunoglobulin-E therapy.
Patients aged six to 80 years were enrolled across nine countries between 2022 and 2024 and were randomised to receive dupilumab or placebo in addition to background antihistamines for 24 weeks.
LIBERTY-CSU CUPID-C cohort
The CUPID-C cohort included 151 participants (mean age 44.7 years, 70.2% female). More than half (51%) were taking antihistamines at higher-than-recommended doses, and 59.6% had severe disease activity at baseline, defined as a Urticaria Activity Score over seven days (UAS7) of ≥28.
Dupilumab dosing was determined by weight. Adults and adolescents weighing ≥60 kg received a 600 mg loading dose followed by 300 mg every two weeks. Adolescents weighing <60 kg and children ≤30 kg received a 400 mg loading dose followed by 200 mg every two weeks, while children weighing 15 to <30 kg received a 600 mg loading dose followed by 300 mg every four weeks.
At week 24, dupilumab significantly improved both itch severity and overall CSU activity compared with placebo. The least-squares mean change in the Itch Severity Score over seven days (ISS7) was −8.64 with dupilumab versus −6.10 with placebo (difference −2.54 points; 95% CI −4.65 to −0.43; P = 0.02).
Similarly, UAS7 improved with dupilumab (difference −4.65 points vs placebo; 95% CI −8.65 to −0.65; P = 0.02).
Pooled trial data confirm dupilumab efficacy
Pooling results from CUPID-A and CUPID-C created a combined dataset of 289 patients with CSU and strengthened the evidence base. In this analysis, dupilumab again showed superior symptom improvement: ISS7 decreased by −9.94 with dupilumab compared with −6.71 with placebo, while UAS7 decreased by −19.29 versus −13.13, respectively (both P < 0.001).
Clinical responses were apparent from week 3. By week 24, 43.1% of patients treated with dupilumab achieved well-controlled disease (UAS7 ≤6) compared with 23.4% receiving placebo, and 30.6% reached complete symptom control (UAS7 = 0) versus 15.9% in the placebo group.
A clinically meaningful reduction in itch severity (≥5-point reduction in ISS7) was observed in 70.3% of patients treated with dupilumab, compared with 51.9% of those on placebo, in the CUPID-C trial.
The treatment was generally well tolerated. In the combined analysis, 53.5% of dupilumab recipients and 55.9% of the placebo group experienced treatment-emergent adverse events. The most commonly reported events were nasopharyngitis and exacerbations of CSU. Serious adverse events occurred in 4.9% of the dupilumab group and 4.1% with the placebo.
Several limitations should be recognised, the authors said, including the 24-week study period, which did not allow for assessment of long-term response stability, and the relatively small number of participants aged six to 18 years. Additionally, the limited racial and ethnic diversity among participants may affect the generalisability of the results.
In conclusion, the authors stated that the CUPID-C trial confirms earlier findings from CUPID-A and that inhibition of the IL-4/IL-13 pathway may be an effective therapeutic approach for patients with CSU who remain symptomatic despite standard antihistamine treatment.
Reference
Casale T et al. Dupilumab in Patients With Chronic Spontaneous Urticaria. Phase 3 LIBERTY-CSU CUPID Randomized Trials. JAMA Dermatol 2026;Feb 18:e256023.
This article was originally published by our sister publication Hospital Healthcare Europe.
