RATIONALE: Previous studies have shown that mepolizumab significantly reduces exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma. This analysis assessed the effect of mepolizumab 100 mg SC on AM PEF based on study entry criteria and by eosinophil thresholds.
METHODS: Post-hoc analysis of data from two randomized, double-blind, placebo-controlled studies (NCT01691521/NCT02281318) of 4-weekly mepolizumab 100 mg (n=454) versus placebo (n=456) in patients with severe eosinophilic asthma. All patients received high dose ICS plus ≥1 controller medication, had ≥2 exacerbations in the previous year and blood eosinophils ≥150 cells/µL at screening or ≥300 cells/µL in the previous year. Data were analyzed using a mixed model repeated measures controlling for multiple covariates.
RESULTS: The mean change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the placebo group, p<0.001. When the population was stratified by eosinophil thresholds the mean difference from placebo was 24 L/min (≥150 cells/µL), 27 L/min (≥300 cells/µL) and 34 L/min (≥500 cells/µL), p<0.001 for all sub-groups. The <150 cells/µL (300 cells/µL in the previous year) group increased 13 L/min, while both 150 to <300 cells/µL and 300 to <500 cells/µL ranges demonstrated comparable changes (19 L/min and 17 L/min) compared to placebo, respectively.
CONCLUSIONS: Our analysis showed significant improvements with mepolizumab 100 mg SC in lung function measured by AM PEF in patients with severe eosinophilic asthma. In addition, the data suggest that higher eosinophil counts are associated with greater improvements in AM PEF.