Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase IIb multinational randomized double-blind placebo-controlled ARROYO trial
Authors: Altrichter Sabine , Giménez-Arnau Ana Maria , Bernstein Jonathan A , Metz Martin , Bahadori Lila , Bergquist Maria , Brooks Laura , Ho Calvin N , Jain Priya , Lukka Pradeep B , Rodriguez-Suárez Eva , Walton Claire , Datto Catherine J ,   ARROYO Study Investigators, Vekovska Kamelia , Leflein Jeffrey , Stoyanova Genova Sonya , Mandazhieva - Pepelanova Mariana , Nittner Marszalska Marita , Hofman Anna , Gimenez Arnau Ana Maria , Tan Ricardo , Noguchi Hiromitsu , Oda Yoshiko , Kume Akihiro , Seo Seong Jun , Szymanska Elzbieta , Silvestre Salvador Juan Francisco , Bernstein Jonathan , Yamamoto Aisaku , Carr Warner , Mateev Grisha , Treudler Regina , Klein Ryan , Waibel Jill , Imko Walczuk Beata , Dencheva Rositsa , Park Young Min , Takahagi Shunsuke , Pulka Grazyna , Stanev Plamen , Bauer Andrea , Vasileva Irida , Kim Tae Gyun , Lopez Bran Eduardo , Metz Martin , Ruano Ruiz Juan Alberto , Calatayud Antonio Martorell , Richardson Blakely , Steil Kenneth , Lam Yaohan , Cartwright Robert , Lynn Lon , Assaad Amal 
Published: February 2024

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-α 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, randomized, double-blind, placebo-controlled, phase IIb portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomized 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 Itch Severity Score (ISS)7 at week 12. The key secondary endpoint was change from baseline in Urticaria Activity Score (UAS)7 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 randomized 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 (CI) −3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference –1.79, 95% CI –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 = 0.407; benralizumab 60 mg vs. placebo, P = 0.082). 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.