The effect of biologics on lung function improvements among severe eosinophilic asthma patients with partial reversibility or fixed obstructive defects: A retrospective analysis

Background The management of SEA has evolved since the introduction of biologics in 2015, with clinical trials demonstrating reduced exacerbations and enhanced lung function. However, these trials typically exclude SEA patients without reversible airway obstruction on PFTs. This exclusion is significant, as many real-world SEA patients exhibit fixed or partially reversible obstruction, thus raising questions about the effectiveness of the use of biologics for treatment in this subgroup. Objectives We aimed to evaluate whether SEA patients with fixed or partially reversible airway obstruction who are treated with mepolizumab or benralizumab demonstrate improvements in lung function in real-world practice. Demographic and laboratory variables, asthma control indicators, and the frequency of exacerbations were also compared between the two biologics. Methods We retrospectively analyzed SEA patients receiving mepolizumab or benralizumab for ≥ 12 months in Central Florida, USA, between January 2018 and January 2023. EMRs were reviewed to extract demographic, lung function, laboratory, medication, and exacerbation data. Results Among 195 subjects (median age = 60 years), mepolizumab and benralizumab were used by 109 (55.9%) and 86 (44.1%) patients, respectively. The majority of the included patients were female (83.1%) and Hispanic (45.1%). Biologic therapy led to modest lung function improvement, with median changes in FVC of 30 mL (p < 0.031) and median changes in FEV1 of 50 mL (p < 0.002). Most patients (81%) experienced no exacerbations over 12 months. Asthma symptom improvement was nonsignificant (mean change in ACT = 3, p = 0.252). Stratified analyses revealed that improvements in FVC and FEV1 were significant in the benralizumab group (p = 0.020) but not the mepolizumab group (p = 0.196). There were no significant differences in any other parameters between the groups. Conclusions SEA patients with fixed or partially reversible obstruction are generally excluded from clinical trials but experienced modest lung function improvement after treatment with biologics in the current trial. This finding indicated the potential effectiveness of biologics in this subgroup, thus underscoring the importance of further research in real-world patient populations that are often omitted from clinical trials. Clinical trial number : Not applicable.