Francesco Menzella,1 Marco Bonavia,2 Matteo Bonini,3 Maria D’Amato,4 Salvatore Lombardo,5 Nicola Murgia,6 Vincenzo Patella,7,8 Massimo Triggiani,9 Girolamo Pelaia10 1Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS, Reggio Emilia, Italy; 2Pneumologia Riabilitativa - Ospedale Ge-Arenzano, ASL3-, Genoa, Italy; 3Department of Cardiovascular and Thoracic Sciences, Università Cattolica del Sacro Cuore, Rome, Italy; 4Respiratory Department- Monaldi Hospital AO Dei Colli, Naples, Italy; 5Pneumology Unit, Ospedale Giovanni Paolo II, Lamezia Terme, Italy; 6Section of Occupational Medicine, Respiratory Diseases and Toxicology, University of Perugia, Perugia, Italy; 7Division of Allergy and Clinical Immunology, Department of Medicine ASL Salerno, Santa Maria Della Speranza Hospital, Salerno, Italy; 8Postgraduate Program in Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy; 9Division of Allergy and Clinical Immunology, University of Salerno, Fisciano, Italy; 10Department of Health Sciences, Respiratory Unit, University “Magna Graecia” of Catanzaro, Catanzaro, ItalyCorrespondence: Francesco MenzellaPneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS, Reggio Emilia, ItalyTel +390522296073Email Francesco.Menzella@ausl.re.itPurpose: Severe eosinophilic asthma (SEA) is characterized by high eosinophilia, severe symptoms, important comorbidities, frequent exacerbations, and poor asthma control. Benralizumab, targeting the interleukin-5 receptor alpha, proved effective in inducing rapid eosinophil depletion and amelioration of symptoms and lung function; it also allowed to reduce exacerbations and the use of oral corticosteroids (OCS). The present case series, spanning different subtypes of SEA, aimed at expanding the real-world experience with benralizumab in Italy.Patients and Methods: We collected data from SEA patients treated with benralizumab, at baseline and during treatment. We focused on the effects of benralizumab in the following conditions and endpoints: i) overlap between high-IgE and high-eosinophilic asthma; ii) presence of nasal polyposis as comorbidity; iii) corticosteroid-sparing effect; iv) patient perception.Results: Ten SEA patients (females: N=7; age range: 19– 70 years) referred to 8 Italian Centers and treated with benralizumab were included, presenting with several comorbidities such as non-allergic disease (8/10), atopy (3/10), high IgE (5/10) and nasal polyposis (6/10). Overall, benralizumab yielded optimal disease control in all patients, particularly in terms of rapid clinical and functional improvement, decreased systemic steroid need (OCS therapy was completely discontinued in 7 cases) and amelioration of patient quality of life, except for 1 case, in whom other conditions not related to benralizumab therapy interfered with the patient perception.Conclusion: Our findings further support the efficacy and safety of benralizumab observed in randomized clinical trials, providing even better results for lung function improvement.Keywords: benralizumab, IL-5 receptor, oral corticosteroids, overlap IgE/eosinophilic asthma, polyposis, real world, severe eosinophilic asthma