Treatment of Chronic Spontaneous Urticaria With Benralizumab: Report of
Primary Endpoint Completer Analysis, Secondary and Exploratory Endpoints
Background. Standard of care for chronic spontaneous urticaria (CSU)
includes second-generation H1-antihistamines (SGAH) but is often
ineffective even with four-times the FDA-recommended dose. Urticarial
lesions are commonly characterized by increased lymphocytes with
perivascular eosinophilic infiltrates implying a role for the
interleukin-5 (IL5). Objective. This study investigated the effects of
benralizumab, an anti-IL5-receptor-alpha monoclonal antibody, in human
subjects with SGAH-unresponsive CSU that completed all study visits.
Methods. A repeated-measures, 24-week study was conducted at an
urticaria specialist clinic where SGAH-unresponsive CSU patients (3
males and 9 females; age range, 32-65 years) having a median weekly
Urticaria Activity Score (UAS7) of 4 and pruritus severity ≥2 were
enrolled. After a baseline run-in period, subjects were treated with a
subcutaneous placebo dose followed by benralizumab 30mg subcutaneously
every month (×3 doses) followed by two off-medication monthly-visits.
The primary and exploratory endpoints were the change from baseline in
UAS7 and Chronic Urticaria Quality-of-Life Score (CU-QoLTS)
respectively. Secondary endpoints included peripheral blood eosinophils
(eos%) and basophils, skin eosinophilia, and differentially expressed
genes (DEGs) in blood before- and after benralizumab. Results. UAS7 and
CU-QoLTS significantly improved post-benralizumab compared to baseline
scores in 7 of 9 subjects completing the study. Clinical improvements
correlated with reduction in eos% and inflammatory cell infiltrates in
skin lesions. Biologic pathways, regulated by DEGs, involved IL-5R
activity, tryptophan metabolism and Siglec-8 expression. Conclusion.
Benralizumab was clinically efficacious in the treatment of subjects
with SGAH-refractory CSU which correlated with several DEGs in blood.
This study supports the use of benralizumab for CSU treatment.