BACKGROUND: A transient and usually asymptomatic increase in blood eosinophil count (BEC) associated with dupilumab treatment has been described. Predicting factors related to the increase in BEC and the occurrence of symptoms are still poorly investigated. OBJECTIVE: To investigate frequency, timing, duration, clinical relevance, and potential predictors of the increase in BEC in a real-life multicenter cohort of patients affected by asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab. METHODS: BEC and clinical conditions at baseline and every 3 months after the start of dupilumab treatment were assessed. Any adverse drug reaction was also recorded. Remission of dupilumab-associated eosinophilia was defined by follow-up BEC values <
0.5 × 10 RESULTS: Overall, 108 of 195 (55%) patients experienced an increased BEC after dupilumab initiation, but only 29 of 195 (14.9%) showed hypereosinophilia. BEC peak occurred 6 months after the start of treatment and resolved after 9 months (median time). The probability of developing hypereosinophilia was 3.3 times higher in patients with the baseline BEC between 0.5 × 10 CONCLUSIONS: In a real-life setting, dupilumab treatment in patients with asthma and/or CRSwNP was often associated with a transient increase in BEC, but hypereosinophilia rarely occurred. Onset of symptoms co-occurring with BEC peak was observed in a minority of subjects. BEC should not preclude dupilumab initiation or continuation but should be monitored for at least 8 months after treatment begins, particularly in the case of baseline eosinophilia/hypereosinophilia and/or comorbidities.