Treatment of chronic spontaneous urticaria with benralizumab: Report of primary endpoint per‐protocol analysis and exploratory endpoints

Abstract

To the Editor, Standard treatments for chronic spontaneous urticaria (CSU) including the second-generation H1-antihistamines (SGAH) are often ineffective even with four times the FDA-recommended dose. 1,2 Eosinophilic infiltrates and an abundance of interleukin-5 (IL5) in CSU lesions (hives) support a role for IL5 in the pathomechanism(s) of CSU. 3 Thus, the use of biologic therapies, for example, benralizumab targeting IL5-receptor-α, in treating SGAH-resistant CSU was hypothesized.A repeated-measures, 24-week study was designed and conducted at an urticaria clinic to determine clinical efficacy of benralizumab in CSU. Twelve SGAH-unresponsive CSU patients (3 males, 9 females; 2 blacks, 10 whites; between ages 32-65 years) having a median daily Urticaria Activity Score (UAS7) 4 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 30 mg subcutaneously every month (×3 doses) followed by two off-medication monthly visits. Subject-reported responses to UAS7 and CU-QoL questionnaires were recorded at the monthly visits. The primary and exploratory endpoints were the change in UAS7 and Chronic Urticaria Quality-of-Life Total Score (CUQoLTS) respectively, from 4 weeks after placebo dose (visit 2) to 4 weeks after last dose of benralizumab (visit 5). Nine subjects completed

Chronic spontaneous urticaria: Focus on pathophysiology to unlock treatment advances

“…Targeting IL‐5, either directly or via its signaling pathway, may therefore provide additional treatment modalities for CSU. Various reports of the clinical efficacy of mepolizumab 92 and benralizumab 93,94 support this approach, with both agents currently undergoing clinical trials in patients with CSU 95,96…”

“…22,23,91 Targeting IL-5, either directly or via its signaling pathway, may therefore provide additional treatment modalities for CSU. Various reports of the clinical efficacy of mepolizumab 92 and benralizumab 93,94 support this approach, with both agents currently undergoing clinical trials in patients with CSU. 95,96 Another type of crosstalk appears to occur between activated eosinophils and MCs, with eosinophils secreting proteins that regulate MCs, such as eosinophil cationic protein (ECP), eosinophil peroxidase, and major basic protein.…”

Case of benralizumab‐induced exacerbations of chronic spontaneous urticaria

“…The anti‐interleukin‐5 monoclonal IL‐5‐ (IL‐5) receptor‐α antibody benralizumab is currently proposed as one of the drugs for the treatment of patients with severe chronic spontaneous urticaria (CSU). 1 The rationale for using targeted therapy against IL‐5 in CSU is the eosinophilic infiltrates and the presence of IL‐5 in CSU hives, suggesting that IL‐5 plays a role in the pathophysiology of CSU. 1 , 2 , 3 Here, we report a patient with CSU and concurrent severe eosinophilic asthma in whom benralizumab exacerbated CSU.…”

“… 1 The rationale for using targeted therapy against IL‐5 in CSU is the eosinophilic infiltrates and the presence of IL‐5 in CSU hives, suggesting that IL‐5 plays a role in the pathophysiology of CSU. 1 , 2 , 3 Here, we report a patient with CSU and concurrent severe eosinophilic asthma in whom benralizumab exacerbated CSU. Type I hypersensitivity to benralizumab was ruled out by a negative skin prick and intradermal test.…”

Prurigo Nodularis: Pathogenesis and the Horizon of Potential Therapeutics

“…Additionally, the IGA stage was 0 or 1 in 30.4% of patients in the vixarelimab group (versus 7.7% in the placebo group; p < 0.03) at week 8. Adverse events in the vixarelimab arm included upper respiratory tract infections (21.7% of patients), nasopharyngitis (13.0% of patients), nummular eczema, and urticaria (each 8.7% of patients) [232].…”