Exacerbation Reduction in Severe Eosinophilic Asthma Based on Eosinophil Thresholds

Rationale: Previous studies showed mepolizumab significantly reduces exacerbations in patients with severe eosinophilic asthma. This study assessed the effect of mepolizumab on the frequency of exacerbations in severe eosinophilic asthma based on different baseline blood eosinophil thresholds.

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)