Dupilumab Beneficial When Antihistamines Fall Short for CSU

The addition of dupilumab significantly reduced itching and hives compared with placebo in patients with chronic spontaneous urticaria (CSU) that was uncontrolled with H1-antihistamines, based on data from 151 individuals.

“Approximately 50% of patients with chronic spontaneous urticaria do not respond to antihistamines,” said Thomas B. Casale, MD, professor of internal medicine at the University of South Florida, Tampa, Florida, in an interview. Omalizumab, the only biologic approved for this condition, is not effective in all patients, and additional treatment options are needed, said Casale, the lead author who presented the new data at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Annual Scientific Meeting.

Dupilumab (Dupixent), a fully human monoclonal antibody that targets the interleukin (IL)-4 and IL-13 pathways, is currently approved in the United States for the treatment of several allergy and dermatology indications, including atopic dermatitis, severe asthma exacerbations, chronic rhinosinusitis with nasal polyps, and prurigo nodularis.

In the study, known as LIBERTY-CSU CUPID Study C, researchers randomized 74 patients with CSU aged 6 years or older to add-on dupilumab subcutaneously every 2 weeks and 77 to placebo. (Patients were omalizumab-naive and had symptomatic CSU, despite treatment with up to four times the approved dose of standard-of-care H1-antihistamines.) Dupilumab doses were 300 mg for adults and adolescents weighing ≥ 60 kg or 200 mg for adolescents weighing

The primary outcomes were Itch Severity Score over 7 days (ISS7; range, 0-21) and Urticaria Activity Score over 7 days (UAS7; range, 0-42).

Over the 24-week study period, patients in the dupilumab group showed significantly greater change from baseline than those in the placebo group on both measures, with least squares mean changes of 8.6 vs 6.1 for ISS7 and 15.9 vs 11.2 for UAS7 (P = .02 for both).

In addition, at 24 weeks, significantly more patients in the dupilumab group than in the placebo group achieved well-controlled disease based on a UAS of 6 or lower (41% vs 23%; P = .005). Significantly more dupilumab-treated patients also achieved a complete response (defined as a UAS of 0) compared with placebo-treated patients (30% vs 18%; P = .02).

Overall rates of treatment-emergent adverse events were 53% for both groups, and safety data were mainly consistent with dupilumab’s known safety profile, the researchers wrote.

The findings were not surprising, as a previous related study, LIBERTY-CSU CUPID Study A, showed that dupilumab was effective for CSU, Casale told Medscape Medical News. “This replicate study confirms the previous study and provides evidence for regulatory approval,” he said.

If approved by the US Food and Drug Administration (FDA), “dupilumab will provide another therapeutic option for patients with chronic urticaria unresponsive to antihistamines,” Casale commented.

No new safety signals occurred, and the ability to self-administer the medication at home provides an advantage for patients, he added. As for additional research, “analysis of patient characteristics and potential biomarkers that would predict responsiveness is needed.”

More Research Needed to Fine-Tune Management

An unmet need persists for patients with CSU whose disease is not adequately controlled by higher-dose H1-antihistamines, Robert G. Micheletti, MD, associate professor of dermatology and medicine at the University of Pennsylvania, Philadelphia, said in an interview. “It is important not only to identify effective add-on therapies for these patients but also to generate data to support insurance coverage and drug access,” said Micheletti, who was not involved in the study.

Also referring to the similar findings reported in the LIBERTY-CSU CUPID Study A, Micheletti said, “as in the earlier study, the results demonstrate significantly reduced itch and urticaria in treated patients compared to placebo.”

“While many providers currently prescribe dupilumab off-label for refractory CSU, FDA approval would improve access to the drug for patients who need it and provide an alternative for patients who may not be good candidates for omalizumab,” he added. However, more research is needed to define optimal management of patients with CSU with inadequate response to omalizumab, he said.

“The LIBERTY-CSU CUPID Study B showed a small improvement in itch severity and urticaria activity among such patients receiving dupilumab,” he noted. “Future work should aim to identify biomarkers and other features predictive of response to various therapies,” Micheletti added.

Study B involved patients with CSU who were uncontrolled on standard-of-care antihistamines and refractory or intolerant to omalizumab, according to Regeneron. On November 15, after the ACAAI meeting had ended, the company announced that the FDA had accepted the resubmission of an application for approval of dupilumab for the treatment of CSU in adults and pediatric patients aged 12 years or older not adequately controlled with H1-antihistamines.

The study was supported and sponsored by Sanofi and Regeneron Pharmaceuticals. Casale disclosed serving as a consultant for ALK, ARS Pharma, AstraZeneca, Bryn Pharma, Celgene, Eli Lilly, Genentech, GSK, Jasper, Novartis, Regeneron, and Sanofi and as a speaker for Genentech and Regeneron. Micheletti had no relevant financial conflicts to disclose.