D2.137 - Long term, Persistent Eosinophilia in patients with Asthma and CRSwNP undergoing Dupilumab therapy: preliminar results of a 24-month follow up prospective study

Dupilumab is a human monoclonal antibody targeting both IL-4 and IL-13 signaling approved for treatment of T2 severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis and eosinophilic esophagitis.  Dupilumab induced (hyper)-eosinophilia described in clinical trials and real-life studies is reported as rare, early and transient. The aim of our study is to assess baseline characteristics, response to treatment and practical management in a cohort of patients presenting persistent (hyper)-eosinophilia during Dupilumab therapy over a 24-month follow-up period.

We enrolled 64 (age 18-83) years patients diagnosed with asthma and/or CRSwNP undergoing Dupilumab treatment.  Demographic characteristics, ACT, SNOT-22, TENPS, blood eosinophilia, IgE levels, NSAIDs and Type 2 comorbidities were assessed at baseline and at 3, 6, 12, 18, and 24 months post-Dupilumab initiation focusing on blood eosinophilia trends and clinical and safety outcomes. To investigate potential eosinophilic related morbidities, an expert-based algorithm was adopted in patients with dupilumab induced (hyper)-eosinophilia.

Persistent fluctuating (hyper)-eosinophilia [500-4800/mmc] lasting more than 6 months (on average, 12 months) and occurring often after the first 6 months of therapy (on average, 6 months) was observed in 16 out of 64 patients (25%). In these patients, a long, stepwise based monitoring was performed to exclude eosinophilic disorders or secondary causes of eosinophilia. No symptoms or signs of eosinophilic-related organ damage has been observed. None of these patients discontinued Dupilumab as drug administration was safe and associated with amelioration of clinical outcomes. Correlation between baseline characteristics of our cohort and drug induced persistent (hyper)-eosinophilia is still under evaluation.

Long term, persistent (hyper)-eosinophilia during Dupilumab treatment occurred in a high percentage of our patients in the absence of symptoms or signs of hypereosinophilic damage. A prudent monitoring avoided treatment discontinuation while maintaining efficacy and safety.  Future research should better focus on the long-term impact of sustained eosinophilia and its relevance in clinical practice.