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.
Journal
The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041
Informations de publication
Date de publication:
17 Feb 2024
17 Feb 2024
Historique:
received:
06
12
2023
revised:
02
02
2024
accepted:
15
02
2024
medline:
17
2
2024
pubmed:
17
2
2024
entrez:
17
2
2024
Statut:
aheadofprint
Résumé
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. To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment. 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. 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. Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.
Sections du résumé
BACKGROUND
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
OBJECTIVE
To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment.
METHODS
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
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
CONCLUSIONS
Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.
Identifiants
pubmed: 38367194
pii: 7609932
doi: 10.1093/bjd/ljae067
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Kamelia Vekovska
(K)
Jeffrey Leflein
(J)
Sonya Stoyanova Genova
(SS)
Mariana Mandazhieva-Pepelanova
(M)
Marita Nittner Marszalska
(MN)
Anna Hofman
(A)
Ana Maria Gimenez Arnau
(AMG)
Ricardo Tan
(R)
Hiromitsu Noguchi
(H)
Yoshiko Oda
(Y)
Akihiro Kume
(A)
Seong Jun Seo
(SJ)
Elzbieta Szymanska
(E)
Juan Francisco Silvestre Salvador
(JFS)
Jonathan Bernstein
(J)
Aisaku Yamamoto
(A)
Warner Carr
(W)
Grisha Mateev
(G)
Regina Treudler
(R)
Ryan Klein
(R)
Jill Waibel
(J)
Beata Imko Walczuk
(BI)
Rositsa Dencheva
(R)
Young Min Park
(YM)
Shunsuke Takahagi
(S)
Grazyna Pulka
(G)
Plamen Stanev
(P)
Andrea Bauer
(A)
Irida Vasileva
(I)
Tae Gyun Kim
(TG)
Eduardo Lopez Bran
(EL)
Martin Metz
(M)
Juan Alberto Ruano Ruiz
(JAR)
Antonio Martorell Calatayud
(AM)
Blakely Richardson
(B)
Kenneth Steil
(K)
Yaohan Lam
(Y)
Robert Cartwright
(R)
Lon Lynn
(L)
Amal Assaad
(A)
Informations de copyright
© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.