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
Sabine Altrichter, Ana M. Giménez‐Arnau, Jonathan A. Bernstein, Martin Metz, Lila Bahadori, Maria Bergquist, Laura Brooks, Calvin N. Ho, Priya Jain, Pradeep B. Lukka, Eva Rodríguez‐Suárez, Claire Walton, Catherine Datto, ARROYO Study Investigators, Kamelia Vekovska, Jeffrey Leflein, Sonya Genova, Mariana Mandazhieva - Pepelanova, Marita Nittner Marszalska, Anna Hofman, Ana M. Giménez‐Arnau, Ricardo Tan, Hiromitsu Noguchi, Yoshiko Oda, Akihiro Kume, Seong Jun Seo, Elżbieta Szymańska, J.F. Silvestre, Jonathan A. Bernstein, Aisaku Yamamoto, Warner Carr, Grisha Mateev, Regina Treudler, Ryan Klein, Jill Waibel, Beata Imko Walczuk, Rositsa Dencheva, Young Min Park, Shunsuke Takahagi, Grażyna Pulka, Plamen Stanev, Andrea Bauer, Irida Vasileva, T. Kim, Eduardo López Bran, Martin Metz, Juan Alberto Ruano Ruiz, Antonio Martorell Calatayud, Blakely Richardson, Kenneth Steil, Yaohan Lam, Robert Cartwright, Lon Lynn, Amal Assa’ad
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.