David N Pham1. 1. Allianz Research Institute, 14120 Beach Blvd, Suite 101, Westminster, CA, USA. david.pham@allianzresearch.com.
Abstract
BACKGROUND: T cell-mediated eosinophilia is associated with numerous conditions-including atopic dermatitis, food allergies, and asthma-collectively known as the "atopic march." Benralizumab is a recombinant, humanized, afucosylated monoclonal antibody directed against the ⍺ chain of the eosinophil cell surface receptor IL-5R. Benralizumab treatment causes near-complete depletion of circulating eosinophils and was approved in 2017 for add-on, maintenance treatment of severe asthma with an eosinophilic phenotype, based on the results of the CALIMA and SIROCCO pivotal trials. Benralizumab is not currently approved for the treatment of eosinophilic conditions besides asthma; however, during the CALIMA trial, spontaneous resolution of atopic dermatitis was observed in a patient, concurrent with reduction in her asthma symptoms. CASE PRESENTATION: In January 2015, a 14-year-old Asian girl with severe, uncontrolled asthma was enrolled in CALIMA. The patient's baseline eosinophil blood count was 1200 cells/μL, her pre-bronchodilator forced expiratory volume in 1 second (FEV1) was 1.9 L and FEV1/forced vital capacity (FVC) ratio was 71.4%, and her post-bronchodilator FEV1 was 3.2 L (FEV1/FVC of 115.9%). Her overall baseline asthma symptom score was 3.9 and her asthma exacerbation rate in the prior year was 4. She also displayed a pronounced, pruritic, chronic, inflammatory rash consistent with atopic dermatitis across her face. The investigator was blinded to the patient's treatment group during treatment; however, her asthma symptoms diminished over the course of the study (FEV1 at 56 weeks, 3.01 L/110.5% (pre) and 3.25 L/119.3% (post); overall asthma symptom score 2.1; one influenza-associated exacerbation). Furthermore, her atopic dermatitis symptoms resolved spontaneously within the first 5 months of the study. After unblinding, the patient was confirmed to have been randomized to an active treatment arm, and her blood eosinophil count had dropped below the limit of detection after the first study dose. CONCLUSIONS: Given the potential shared mechanisms between eosinophilic asthma and atopic dermatitis, it is plausible that benralizumab-induced eosinopenia factored into the resolution of the patient's atopic dermatitis. Further clinical studies are warranted to determine whether benralizumab or other drugs targeted against IL-5/IL-5R may be useful in managing multiple conditions associated with eosinophilia.
BACKGROUND: T cell-mediated eosinophilia is associated with numerous conditions-including atopic dermatitis, food allergies, and asthma-collectively known as the "atopic march." Benralizumab is a recombinant, humanized, afucosylated monoclonal antibody directed against the ⍺ chain of the eosinophil cell surface receptorIL-5R. Benralizumab treatment causes near-complete depletion of circulating eosinophils and was approved in 2017 for add-on, maintenance treatment of severe asthma with an eosinophilic phenotype, based on the results of the CALIMA and SIROCCO pivotal trials. Benralizumab is not currently approved for the treatment of eosinophilic conditions besides asthma; however, during the CALIMA trial, spontaneous resolution of atopic dermatitis was observed in a patient, concurrent with reduction in her asthma symptoms. CASE PRESENTATION: In January 2015, a 14-year-old Asian girl with severe, uncontrolled asthma was enrolled in CALIMA. The patient's baseline eosinophil blood count was 1200 cells/μL, her pre-bronchodilator forced expiratory volume in 1 second (FEV1) was 1.9 L and FEV1/forced vital capacity (FVC) ratio was 71.4%, and her post-bronchodilator FEV1 was 3.2 L (FEV1/FVC of 115.9%). Her overall baseline asthma symptom score was 3.9 and her asthma exacerbation rate in the prior year was 4. She also displayed a pronounced, pruritic, chronic, inflammatory rash consistent with atopic dermatitis across her face. The investigator was blinded to the patient's treatment group during treatment; however, her asthma symptoms diminished over the course of the study (FEV1 at 56 weeks, 3.01 L/110.5% (pre) and 3.25 L/119.3% (post); overall asthma symptom score 2.1; one influenza-associated exacerbation). Furthermore, her atopic dermatitis symptoms resolved spontaneously within the first 5 months of the study. After unblinding, the patient was confirmed to have been randomized to an active treatment arm, and her blood eosinophil count had dropped below the limit of detection after the first study dose. CONCLUSIONS: Given the potential shared mechanisms between eosinophilic asthma and atopic dermatitis, it is plausible that benralizumab-induced eosinopenia factored into the resolution of the patient's atopic dermatitis. Further clinical studies are warranted to determine whether benralizumab or other drugs targeted against IL-5/IL-5R may be useful in managing multiple conditions associated with eosinophilia.
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