Targeting eosinophils: severe asthma and beyond

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Recent research in the field of bronchial asthma has mainly focused on eosinophilic disease phenotype. Several trials proved the efficacy and safety profile of eosinophils and interleukin (IL)-5 targeting molecules, currently approved for severe asthma and available on the market. They include mepolizumab and reslizumab, IL-5 blocking molecules, and benralizumab, targeting the IL-5 receptor and eliciting a NK cell-mediated antibody-dependent cellular cytotoxicity against eosinophils. Eosinophilic inflammation represents the common pathophysiological background of several conditions, providing the rationale for the use of the same biologics beyond asthma. Although with different evidence grade, from clinical trials to case reports, anti-IL-5 biologics have been investigated in eosinophilic granulomatosis with polyangitis, allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, nasal polyposis, hypereosinophilic syndrome, and eosinophilic esophagitis.

However, non-negligible differences between asthma and other eosinophilic diseases, particularly in eosinophils homing (blood and/or tissues), target organs and thus clinical features, probably account for the different response to the same drug in different clinical conditions and highlights the need for tailoring the therapeutic approach by modulating the drug dose and/or by combination therapy with multiple drugs.

The optimal safety and tolerability profile of anti-IL-5 drugs warrants further and larger experimental and real-life investigations, which are needed especially in the field of non-asthma eosinophilic diseases.

This review aims at summarizing the rationale for the use of biologics in eosinophilic diseases and their mechanisms of action. The current efficacy and safety evidence about eosinophils and IL-5 targeting molecules in asthma and in eosinophilic conditions beyond bronchi is also discussed.

Keywords: ABPA, benralizumab, EGPA, eosinophilic esophagitis, eosinophilic inflammation, mepolizumab, reslizumab, severe asthma.

Citation: Caminati M, Menzella F, Guidolin L, Senna G. Targeting eosinophils: severe asthma and beyond. Drugs in Context 2019; 8: 212587. DOI: 10.7573/dic.212587

Contributions: MC and GS conceived the manuscript outline, contributed to all the sections and revised the whole manuscript. FM drafted
the paragraphs concerning severe asthma. LG drafted the paragraphs concerning eosinophilic diseases. All the authors read and approved the
final version. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take
responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at

Acknowledgements: None.

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2019 Caminati M, Menzella F, Guidolin L, Senna G. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2019 Caminati M, Menzella F, Guidolin L, Senna G. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

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Correspondence: Marco Caminati, Department of Medicine, University of Verona, and Asthma Center and Allergy Unit, Verona University
Hospital, Piazzale Scuro 10, 37134 Verona, Italy.

Provenance: invited; externally peer reviewed.

Submitted: 18 March 2019; Peer review comments to author: 17 May 2019; Revised manuscript received: 30 May 2019; Accepted: 3 June 2019; Publication date: 23 July 2019.

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