Benralizumab for Chronic Spontaneous Urticaria

Bernstein, Jonathan A.; Singh, Umesh; Rao, Marepalli B.; Berendts, Karen; Zhang, Xiang; Mutasim, Diya F.

doi:10.1056/nejmc2016395

Cited by 62 publications

(33 citation statements)

References 5 publications

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“…Furthermore, an overall difference of UAS7 greater than the MDC value of 14.7 between baseline and end of study post-benralizumab treatment implies that this finding is also clinically meaningful (Table 1) . These results are consistent with the intentto-treat primary endpoint analysis recently reported 24 . Comparison of benralizumab responders (n=7) to non-responders (n=2) revealed that the average baseline UAS7 among treatment responders was less than non-responders, although this difference was not statistically significant (27 vs. 37.5, p=0.5).…”

Section: Discussionsupporting

confidence: 92%

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Treatment of Chronic Spontaneous Urticaria With Benralizumab: Report of Primary Endpoint Completer Analysis, Secondary and Exploratory Endpoints

Singh¹,

Bernstein²,

Rao³

et al. 2020

Preprint

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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 SGAHunresponsive 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.

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Section: Discussionsupporting

confidence: 92%

“…[21][22][23] We have recently reported the intent-to-treat primary endpoint data analysis. 24 Here we now report the primary, secondary and exploratory endpoints of subjects completing all study visits.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Chronic Spontaneous Urticaria With Benralizumab: Report of Primary Endpoint Completer Analysis, Secondary and Exploratory Endpoints

Singh¹,

Bernstein²,

Rao³

et al. 2020

Preprint

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“…Furthermore, no drug-related side events were reported during the study, suggesting a good safety profile. These findings support the use of benralizumab in the treatment of CSU cases that are unresponsive to second-generation H1-antihistamines and provide evidence of a pathogenic role for infiltrating eosinophils [107].…”

Section: Biologics In Chronic Spontaneous Urticariasupporting

confidence: 72%

Immunological Targets of Biologic Drugs in Allergic Skin Diseases in Children

et al. 2021

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Atopic dermatitis and urticaria are two invalidating skin disorders that are very common in children. Recent advances in the understanding of their specific intracellular molecular pathways have permitted the development of precise biological molecules, targeting inflammatory mediators and arresting the pathogenetic pathways of skin diseases. Many biologics with promising results have been studied, although few are currently approved in children. In this review, we aim to provide the latest evidence about the use, indications, efficacy and safety of biologic therapies to treat atopic dermatitis and chronic urticaria in children and adolescents.

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“…Chronic spontaneous urticaria is characterized by recurrent wheals, angioedema, and pruritis for greater than six weeks, with some patients experiencing remitting and relapsing disease over a life span. Although mast cells are considered a signi cant mediator of disease manifestations, benralizumab was shown to be ef cacious in reducing the urticaria activity score [(UAS7), incorporating severity of wheals and pruritus] in patients with persistent disease activity despite antihistamine treatment in a small pilot study (205). This suggests a more prominent role for eosinophils in pathogenesis of this disease (NCT03183024).…”

Section: Eosinophilic Skin Diseasementioning

confidence: 99%

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies

Jacobsen

Jackson

Heffler

et al. 2021

Annu. Rev. Immunol.

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The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Benralizumab for Chronic Spontaneous Urticaria

Cited by 62 publications

References 5 publications

Treatment of Chronic Spontaneous Urticaria With Benralizumab: Report of Primary Endpoint Completer Analysis, Secondary and Exploratory Endpoints

Treatment of Chronic Spontaneous Urticaria With Benralizumab: Report of Primary Endpoint Completer Analysis, Secondary and Exploratory Endpoints

Immunological Targets of Biologic Drugs in Allergic Skin Diseases in Children

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies

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