Effect of Benralizumab on Inflammation in Skin After Intradermal Allergen Challenge in Patients with Moderate-to-severe Atopic Dermatitis

Overview

Journal J Allergy Clin Immunol Glob

Specialty Allergy & Immunology

Date 2024 Sep 5

PMID 39234416

Authors

Christiane E Whetstone

Ruth P Cusack

Emma Price

Karen Howie

Catie Stevens

Dhuha Al-Sajee

Sue Beaudin

Jennifer Wattie

Nadia Alsaji

Abbey Schlatman

Vanessa Luk

Xiaotian Ju

Paul OByrne

Mark Inman

Roma Sehmi

Hermenio Lima

Gail M Gauvreau

Affiliations

Soon will be listed here.

Abstract

Background: Atopic dermatitis (AD) is a skin barrier dysfunction characterized by tissue eosinophilia.

Objective: In patients with AD, we evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in skin after intradermal allergen challenge.

Methods: A total of 20 patients with moderate-to-severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses of benralizumab (30 mg each) administered subcutaneously every 4 weeks (n = 9) with placebo (n = 11). Allergen and saline control intradermal challenges were conducted before and after treatment, with skin biopsy samples collected 24 hours after challenge. Early and late cutaneous responses were measured by skin wheal size. Levels of eosinophils and IL-5 receptor-α-bearing cells, including eosinophil progenitor (EoP) cells, basophils, and mast cells, in papillary dermis were measured by immunofluorescence microscopy, and levels of EoP cells, hematopoietic progenitor cells, and type 2 innate lymphoid cells in the blood were measured by flow cytometry. Outcomes were compared between the placebo and benralizumab treatment groups by using the Mann-Whitney test.

Results: Benralizumab reduced eosinophil counts in the blood ( < .0001) and allergen-challenged skin, as measured by hematoxylin and eosin staining and eosinophil cationic protein antibody concentration ( < .05). Benralizumab lowered the levels of EoP cells, mast cells, and basophils in the skin, as well as the levels of EoP cells, hematopoietic progenitor cells, and type 2 innate lymphoid cells in the blood (all < .05). There was a trend toward improvement in the early cutaneous response ( = .095) but no effect on the late cutaneous response.

Conclusion: In patients with moderate-to-severe AD, benralizumab treatment significantly inhibited accumulation of eosinophils and other IL-5 receptor-α-expressing cells in the papillary dermis after intradermal allergen challenge. Targeting IL-5 receptor-α-positive cells did not modulate the size of the allergen-induced skin wheal (ClincialTrials.gov identifier NCT03563066).

Citing Articles

Regulation of Airway Epithelial-Derived Alarmins in Asthma: Perspectives for Therapeutic Targets.

Hansi R, Ranjbar M, Whetstone C, Gauvreau G Biomedicines. 2024; 12(10).

PMID: 39457624 PMC: 11505104. DOI: 10.3390/biomedicines12102312.

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