Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase 2b multinational, randomised, double-blind, placebo-controlled ARROYO trial

Sabine Altrichter, Ana Maria Giménez-Arnau, Jonathan A Bernstein, Martin Metz, Lila Bahadori, Maria Bergquist, Laura Brooks, Calvin N Ho, Priya Jain, Pradeep B Lukka, Eva Rodriguez-Suárez, Claire Walton, Catherine J Datto, the ARROYO Study Investigators , British Journal of Dermatology, 2024;, ljae067, https://doi.org/10.1093/bjd/ljae067

Abstract

Background

Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils.

Objectives

To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment.

Methods

The 24-week, randomised, double-blind, placebo-controlled, phase 2b portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomised to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in ISS7 at Week 12. The key secondary endpoint was change from baseline in UAS7 at Week 12. Additional secondary endpoints included other metrics to assess CSU at Week 24; blood eosinophil levels; and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups.

Results

Of 155 patients, 59 were randomised to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, least-squares mean difference –1.01, 95% confidence interval –3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference –1.79, 95% confidence interval –4.09 to 0.50) nor in change from baseline in UAS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.4016; benralizumab 60 mg vs. placebo, P = 0.0819). Depletion of blood eosinophil levels was observed at Week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab.

Conclusions

Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.

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