Safety of dupilumab in T2 airways conditions: focus on eosinophilia across trials and real-life evidence

ABSTRACT

Introduction

Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, effectively blocks both IL-4 and IL-13 mediated pathways. Its introduction has represented a significant advancement in the treatment of severe asthma and other Type 2 (T2) conditions, including nasal polyps, atopic dermatitis, and eosinophilic esophagitis. To date, Dupilumab has demonstrated optimal efficacy and safety profile.

Areas covered

The safety profile of dupilumab has been extensively studied, especially for its effects on blood eosinophil count. Transient eosinophil increase during treatment is typically insignificant from a clinical point of view and related to its mechanism of action. Rare cases of hyper-eosinophilia associated with clinical conditions like eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) have been reported. Those cases are often related to the drug’s steroid-sparing effect or the natural trajectory of the underlying disease rather than a direct cause-effect relationship with dupilumab.

Expert opinion

The management of hyper-eosinophilia during dupilumab treatment requires comprehensive diagnostic work-up and strict follow-up monitoring for early detection of systemic disease progression in order to avoid unnecessary discontinuation of an effective treatment. This approach highlights the importance of a personalized treatment.

KEYWORDS:

• Asthma
• chronic rhinosinusitis with nasal polyps
• dupilumab
• EGPA
• eosinophils
• hyper-eosinophilia
• safety
• severe asthma

Article highlights

• Dupilumab for T2 respiratory conditions demonstrated so far an optimal safety and efficacy profile.

• Transient and clinically meaningless variations in eosinophils blood count may occur over dupilumab treatment, related to its mechanism of action.

• Hyper-eosinophilia (> 1500 cells/microliter) has been rarely described and in some cases hyper-eosinophilic dis-immune conditions (EGPA, HES) have been reported to occur, probably more related to dupilumab steroid-sparing effect and/or to disease history evolution according to the ‘eosinophilic march’ hypothesis more than to a cause-effect association with the drug.

• Hyper-eosinophilia management should balance on one side the need of early recognizing and treating potential disease evolution toward systemic involvement, on the other avoiding an unnecessary withdrawal of an effective therapy leading the treated patient to airways disease optimal control.

Declaration of interests

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 on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.