Introduction: No direct ?Head-to-head? trials of comparison between biologics in severe asthma are available.

Aims and Objectives: To define characteristics of a biologic-treated T2 severe asthma population. To evaluate variation of different parameters along biologic treatments and ?Inter-biologic? (Head-to-head) comparison in a real-world setting.

Methods: Demographic, clinical, functional and biological characteristics were evaluated in 104 patients recruited until July 2022 at baseline and over a maximum of 4 years of biologic teraphy (Omalizumab/Oma=41,Mepolizumab/Mepo=26,Benralizumab/Benra=18,Dupilumab/Dupi=19). Head-to-head variations of parameters were assessed.

Results: Overall patients had high prevalence of T2 comorbidities, low mean ACT (17), impaired pulmonary function (FEV1 65%), frequent exacerbations/year (EAs;3.55) and OCS dependance (60%). Dupi-treated patients had lower T2 biomarkers/comorbidities, EAs, worst pulmonary function and more Leukocytes/Neutrophils compared to other biologics. ACT, FEV1%, FVC% improved with all drugs; AEs decreased. OCS were withdrawn in 100% Mepo/Benra, 60% Oma, 28% Dupi. Oma/Benra increased IT%, Oma/Dupi reduced RV. Only Benra lowered Leukocytes/Neutrophils. Head-to-head comparison showed nocturnal awakenings reduction in Benra vs. Oma/Mepo, FVC Delta % post BD increase in Dupi vs. other agents and Neutrophils reduction in Benra/Dupi vs. Oma (All p<0.05).

Conclusions: Dupi-treated patients showed a lower T2 profile and the worst lung function. Response to biologics showed comparable data with literature, with some different evidence. "Head to head" comparison showed the superiority of a single biologic compaired to another with regard to specific traits.