Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management

ABSTRACT

Introduction

Dupilumab is a human monoclonal antibody that targets both IL-4 and IL-13 signaling. It is currently indicated for the treatment of asthma, moderate-to-severe atopic dermatitis, and chronic rhinosinusitis with nasal polyps (CRSwNP). Eosinophilia has been reported as a potential adverse event in treated patients.

Areas covered

A selective search on PubMed and Medline up to January 2022 was performed, by focusing on dupilumab-induced hypereosinophilia described in clinical trials, real-life studies, and case reports. The possible mechanisms underlying dupilumab-induced hypereosinophilia and the eosinophil-related morbidity have also been explored.

Expert opinion

Dealing with dupilumab-induced hypereosinophilia represents a clinical challenge for clinicians managing patients on dupilumab therapy. An algorithm for the practical management of dupilumab-induced hypereosinophilia has been proposed, in order to properly investigate potential eosinophil-related morbidity and avoid unnecessary drug discontinuation.

KEYWORDS:

• Asthma
• atopic dermatitis
• dupilumab
• eosinophils
• algorithm
• hyper-eosinophilia
• IL-4
• IL-13
• nasal polyps

Article highlights

• Dupilumab is a monoclonal antibody that targets both IL-4 and IL-13 signaling and is approved for T2 asthma, atopic dermatitis, and CRSwNP.

• Eosinophilia (AEC ≥ 500/mmc) is a common adverse event reported for dupilumab, and it is usually transient.

• The main pathogenetic hypothesis is that dupilumab inhibits IL-4-/IL-13-induced eosinophil migration from blood into tissues. In fact, IL-4 and IL-13 regulate the expression of chemotactic factors for eosinophils.

• Eosinophil-related organ involvement cannot be accurately predicted by AEC, but close monitoring of the patient and investigation of potential eosinophil-related morbidity are recommended.

• Dealing with dupilumab-induced hypereosinophilia is a recent practical issue for many clinicians who have to manage patients on dupilumab therapy.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded