Biologics in T2 Severe Asthma: Unveiling Different Effectiveness by Real-World Indirect Comparison

Abstract

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.

Keywords: benralizumab; biologics; dupilumab; indirect comparison; mepolizumab; omalizumab; precision medicine; severe asthma; treatable traits.

Figure 1

Solid lines represent the trend of mean paired Delta values calculated from each time point towards T0. Shaded areas cover 95% IC. (A) ACT: asthma control test, (B) nocturnal symptoms, (C) TI % pred.: Tiffeneau index, (D) FVC Delta % post BD, (E) FVC% pred., (F) exacerbations/year, (G) neutrophils, and (H) eosinophils absolute count.

Figure 2

(A–D) Graphics showing for each biologic agent the number of patients who suspended/maintained OCS chronic treatment over years (T0–T4). (A) Omalizumab, (B) mepolizumab, (C) benralizumab, and (D) dupilumab.