Long-Term Efficacy and Safety Among Patients With Severe Eosinophilic Asthma Treated With Mepolizumab and Its Effect on Small Airways

What is already known about this topic? Mepolizumab (MP) is safe and effective in treating patients with severe eosinophilic asthma up to 41/2 years. What does this article add to our knowledge? Our study demonstrates that MP is safe and effective up to 61/2 years. After treatment with MP, all 67 patients in our cohort revealed a 30.4% increase in forced expiratory flow at 25% to 75% (FEF25%_75%) P less than .001. There was a 40% median increase of the FEF25%_75% in 47 super-responders with very little change in the forced expiratory volume in 1 second (FEV1). How does this study impact current management? To effectively manage patients treated with biologics, it is important to follow the FEF25%_75% because this is indicative of small airway disease, which is an integral part of severe eosinophilic asthma. Moreover, all research comparing different biologics, as well as attempts to define a super-responder to various biologics, should include FEF25%_75% rather than just FEV1. BACKGROUND: The major problem at the Cleveland Allergy and Asthma Center was the need for additional therapy for severe eosinophilic asthma patients who were steroid-dependent or required frequent bursts of prednisone.OBJECTIVES: The objectives of this study were to determine the efficacy of monthly mepolizumab (MP) injections up to 61/2 years using Asthma Control Quesitonnaire-7 (ACQ-7), forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25% to 75% (FEF25%_75%) overall and among super-responders, and to understand whether FEF25%_75% is an effective parameter to evaluate MP efficacy.METHODS: We reviewed the charts of 67 patients with severe eosinophilic asthma and compared the results between 47 super-responders and the rest of the cohort regarding ACQ-6, ACQ-7, eosinophils, FEV1, and FEF25%_75%. The groups of super-responders and all other patients were described with respect to initial and current values of the study end points using medians and 25th and 75th percentiles. Changes from the initial to the current values in the study end points were measured using percent changes. The Wilcoxon signed rank test was used within each group to test the null hypothesis of 0 median percent change.RESULTS: After 61/2 years, there were no significant changes in FEV1. The FEF25%_75%, had a significant median percent increase of 40% among the super-responders (P < .001), which was substantially higher (P [ .026) than the median percent increase of 13.8% observed among all other patients.CONCLUSIONS: The use of MP up to 61/2 years was safe and effective, with significant changes to ACQ-7 and FEF25%_75% associated with MP treatment, but not the FEV1. A higher magnitude of changes was observed among super-responders than the rest of the cohort. Changes in FEF25%_75% were more meaningful than changes in FEV1 in evaluating pulmonary function responsiveness of severe eosinophilic asthma to MP.(c) 2023 American Academy of Allergy,