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

Abstract

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 6½ years using Asthma Control Quesitonnaire-7 (ACQ-7), forced expiratory volume in 1 second (FEV₁), forced expiratory flow at 25% to 75% (FEF_25%-75%) overall and among super-responders, and to understand whether FEF_25%-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 FEF_25%-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 6½ years, there were no significant changes in FEV₁. The FEF_25%-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 6½ years was safe and effective, with significant changes to ACQ-7 and FEF_25%-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 FEF_25%-75% were more meaningful than changes in FEV₁ in evaluating pulmonary function responsiveness of severe eosinophilic asthma to MP.

Keywords: ACQ-6; ACQ-7; Asthma; Eosinophilic asthma; Eosinophils; FEF25%–75%; FEV1; Mepolizumab; Pulmonary function tests; Small airway disease; Super-responders; Wilcoxon signed rank test.