BACKGROUND: Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. Its efficacy has been demonstrated in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting. METHODS: We included 12 patients with severe, uncontrolled asthma and dupilumab was chosen if there was at least one evidence of blood eosinophils> 150 cells/ml and/or FeNO>25 ppb during last year. Recent blood eosinophil count report, assessment through ACT, FeNO test and spirometry were performed at baseline and after 3 months of treatment. We calculated also the number of patients achieving a minimal, yet clinically relevant difference in FEV and ACT. RESULTS: After three months of treatment with dupilumab, ACT had a significant improvement (mean ACT pre 13.25±4.65 mean ACT post 19.17±4.45; p<0.01), so as FEV% (mean FEV% pre 62.58±15.73 mean FEV% post 71.00±13.11; p<0.01). FeNO had a significant reduction (median FeNO 32 pre, IQR 19-48.5 median FeNO19 post, IQR 16.5-26), differently from eosinophils blood count (median eosinophils pre 280, IQR 193.8-647.3 median eosinophils post 349.5, IQR 103-836.8; p=0.52). Four patients (33%) had a positive MCID for FEV, and eight patients (67%) had a positive MCID for ACT. CONCLUSIONS: In RCTs performed during clinical development program dupilumab showed an early efficacy in increasing FEV, reducing FeNO and improving asthma control. Our study demonstrates early improvement in asthmatic symptoms, lung function and FeNO in severe type-2 asthma patients after only 3 months of dupilumab biologic therapy. The introduction of FeNO levels evaluation in the selection criteria for dupilumab, further helps the identification of eligible patients among type-2 severe asthma patients and allows a complete outpatient assessment. Further real-life studies with a longer follow up time will be useful to confirm dupilumab efficacy and to promote its use in clinical practice.