Methods: A meta-analysis (GSK ID 204664) of two randomized, double-blind placebo-controlled studies (MEA112997/MEA115588) with mepolizumab or placebo plus standard of care given every 4 weeks in 1192 patients with severe asthma treated with high dose ICS with or without maintenance oral corticosteroids plus a controller, a history of ≥2 exacerbations in the previous year and evidence of eosinophilic inflammation. This post-hoc analysis was conducted using a negative binomial regression model, accounting for study. All mepolizumab doses were combined for this analysis.
Results: The overall reduction in exacerbations with mepolizumab (N=846) compared with placebo (N=346) was 47% (95% CI: 38% to 56%, p<0.001). The exacerbation reduction with mepolizumab compared with placebo based on a threshold ≥150, ≥300, ≥400 and ≥500 was 52% 59%, 66%, 70% respectively. The reduction in exacerbations with mepolizumab vs. placebo based on history of blood eosinophils ≥300 cells/µL in the past year and baseline blood eosinophils <150 cells/mL was 33%.
Conclusions: Mepolizumab significantly reduced the frequency of exacerbations by >50% at different thresholds ≥150 cells/mL. For patients with a baseline eosinophil count <150 cells/mL clinically relevant reductions were observed in those with ≥300 cells/mL in the past year. These results support the use of blood eosinophils as a marker to predict exacerbation reduction with mepolizumab in severe asthma. Funding: GSK (NCT01000506, NCT01691521)