Reduction/elimination of blood eosinophils in severe asthma: should there be a safety consideration?

ABSTRACT

Introduction

Eosinophils play a central role in the inflammation of asthma and are the target of new biologic treatments for patients with severe asthma. Biologics targeting the IL-5 pathway have been shown to reduce asthma exacerbations, improve lung function, reduce oral corticosteroid use, and improve quality of life, accompanied by reduced or even eliminated blood eosinophils. Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of these long-term therapies that reduce or eliminate them.

Areas covered

In this review, we explore the current safety profile of biologics regarding the impact they may have on blood eosinophils, trying to answer the question about any safety consideration.

Expert opinion

Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of long-term therapies that reduce or eliminate these blood cells.

KEYWORDS:

• Severe asthma
• eosinophils
• biologics
• omalizumab
• mepolizumab
• reslizumab
• benralizumab
• dupilumab

Article highlights

• Eosinophils play a central role in the inflammation of asthma.

• Mounting evidence supports that eosinophils carry an antibacterial, antiviral, and antiparasitic role and they interfere with tumor growth.

• Biologics targeting the IL-5 pathway have proven beneficial in severe asthma management.

• Mepolizumab, benralizumab, reslizumab, and dupilumab have a different impact on eosinophil count and function but neither has been linked to concomitant adverse events.

• Existing evidence does not support an increased infection or tumor risk.

This box summarizes key points contained in the article.

4. Expert opinion

There is no doubt that the emergence of specific biologic therapy represents a revolution in severe asthma treatment as the clinical benefit has been clarified through large randomized controlled trials and real-life studies as well. Furthermore, targeting eosinophils through biologic compounds of the IL-5 pathway has shown impressive clinical results irrespective of reduction or elimination of blood eosinophils.

However, is it safe to minimize a naturally existing cell? Theoretically speaking no, but practically the answer seems to be yes. Omalizumab, although not a specific antieosinophilic compound has proved to be safe after more than 15 years of use in everyday clinical practice with no safety reports regarding eosinophils. Mepolizumab has already gained a more than 5 years’ experience and Reslizumab and Benralizumab have data of up to 3 years exposure with acceptable safety regardless of the degree of blood eosinophils decrease or elimination. Two plausible explanations seem to prevail. First, reduction or elimination of blood eosinophils does not mean vanishing eosinophils from the whole body as they are still present in other sites such as tissue airways or bone marrow. Second, as different types of eosinophils may exist, in different kind of condition such as steady state or inflammatory, it is not clear, yet which type of eosinophils is the real target of the IL-5 pathway biologics. If eosinophilic inflammation still constitutes a treatable trait for severe asthma in the future, it is not unlikely to phenotype eosinophils along with the patients.

Despite the different impact of the several biologics on eosinophils depletion, existing evidence does not support an increased infection risk, whereas the risk to benefit ratio, favors the use of IL-5 pathway biologics for severe asthma. Although long term studies are needed, the published evidence up to now supports a convincing anti-eosinophil and anti-IL-5 pathway blockade safety profile.

Declaration of interest

Dr Katsoulis has received fees and honoraria from Novartis, GSK and Astra Zeneca. Dr Kipourou has received fees and honoraria from GSK and Astra Zeneca. Prof Loukides has received fees and honoraria from Novartis, GSK, Astra Zeneca, and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.