Background: Indirect comparison among biologics in severe asthma (SA) is a challenging but desirable goal for clinicians in real life. The aim of the study is to define characteristics of a biologic-treated T2-driven-SA population and to evaluate the effectiveness of biologic treatments in a real-world setting by variation in intra/inter-biologic parameters in an up to 4-year follow-up. Methods: Demographic, clinical, functional, and biological characteristics were evaluated retrospectively in 104 patients recruited until July 2022 at baseline (T0) and over a maximum of 4 years (T4) of biologic therapy (omalizumab/OmaG = 41, from T0 to T4, mepolizumab/MepoG = 26, from T0 to T4, benralizumab/BenraG = 18, from T0 to T2, and dupilumab/DupiG = 19, from T0 to T1). Variations of parameters using means of paired Delta were assessed. Results: At baseline, patients had high prevalence of T2-driven comorbidities, low asthma control test (ACT mean 17.65 ± 4.41), impaired pulmonary function (FEV₁ 65 ± 18 %pred), frequent exacerbations/year (AEs 3.5 ± 3), and OCS dependence (60%). DupiG had lower T2 biomarkers/comorbidities and AEs, and worse FEV₁ (57 ± 19 %pred) compared to other biologics (p < 0.05). All biologics improved ACT, FEV₁%, FVC%, AEs rate, and OCS use. FEV₁% improved in MepoG and BenraG over the minimal clinically important difference and was sustained over 4 years in OmaG and MepoG. A significant RV reduction in OmaG (T4) and DupiG (T1), and BenraG normalization (T2) of airflow limitation were found. We observed through inter-biologic parameters pair delta variation comparison a significant nocturnal awakenings reduction in BenraG vs. OmaG/MepoG, and neutrophils reduction in BenraG/DupiG vs. OmaG. Conclusions: Indirect comparison among biologics unveils clinical and functional improvements that may mark a different effectiveness. These results may highlight the preference of a single biologic compared to another with regard to specific treatable traits.

Introduction: No standardized response criteria exist to biologics in severe asthma. If incomplete, switching can be proposed. Aims and objectives: To evaluate response to 4 different biologics and to describe withdrawals and switches. Methods: 88 severe asthmatic patients treated with biologics (Omalizumab/OMA=41, Mepolizumab/MEPO=23, Benralizumab/BENRA=15, Dupilumab/DUPI=9) were recruited until July 2022. We defined patients “Responder/R”, “Partial Responder/PR” or “Non Responder/NR” based on major/minor criteria. Response was evaluated at year 3 for OMA/MEPO, 2 for BENRA and 1 for DUPI or at withdrawals/switches. Results: R were 56,6 % OMA, 94,7% MEPO, 100 % BENRA and 88,8% DUPI. 17 of 88 patients (10 R, 3 PR, 4 NR) withdrew biologics for poor doctor-assessed efficacy, of which 7 switched to another agent. Other 6 patients switched after a full course of 5 years treatment. We observed: OMA to MEPO (n=3)/BENRA (n=2)/DUPI (n=3), 3 MEPO to DUPI and 2 BENRA to DUPI. 2 patients switched twice (MEPO to DUPI) and 1 switched 3 times (DUPI to BENRA), mostly for uncontrolled nasal polyposis. After switching, patients were all R (n=15)/PR (n=1). Conclusions: Based on our retrospective criteria each biologic showed a high rate of success. OMA response was lower probably because of its first usage that limited the best eligibility based on personalized therapy. Response, despite “criteria label”, should be evaluated “case-by-case”. Switching aimed to reach a complete control on asthma symptoms/comorbidities and occurred mostly from anti-IgE to anti-IL-5/IL-5R/IL-4Rα and from anti IL-5/IL-5R to anti-IL-4Rα.