BACKGROUND: Some patients with severe asthma have frequent exacerbations 
associated with persistent eosinophilic inflammation despite continuous 
treatment with high-dose inhaled glucocorticoids with or without oral 
glucocorticoids.
METHODS: In this randomized, double-blind, double-dummy study, we assigned 576 
patients with recurrent asthma exacerbations and evidence of eosinophilic 
inflammation despite high doses of inhaled glucocorticoids to one of three study 
groups. Patients were assigned to receive mepolizumab, a humanized monoclonal 
antibody against interleukin-5, which was administered as either a 75-mg 
intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 
weeks. The primary outcome was the rate of exacerbations. Other outcomes 
included the forced expiratory volume in 1 second (FEV1) and scores on the St. 
George's Respiratory Questionnaire (SGRQ) and the 5-item Asthma Control 
Questionnaire (ACQ-5). Safety was also assessed.
RESULTS: The rate of exacerbations was reduced by 47% (95% confidence interval 
[CI], 29 to 61) among patients receiving intravenous mepolizumab and by 53% (95% 
CI, 37 to 65) among those receiving subcutaneous mepolizumab, as compared with 
those receiving placebo (P<0.001 for both comparisons). Exacerbations 
necessitating an emergency department visit or hospitalization were reduced by 
32% in the group receiving intravenous mepolizumab and by 61% in the group 
receiving subcutaneous mepolizumab. At week 32, the mean increase from baseline 
in FEV1 was 100 ml greater in patients receiving intravenous mepolizumab than in 
those receiving placebo (P=0.02) and 98 ml greater in patients receiving 
subcutaneous mepolizumab than in those receiving placebo (P=0.03). The 
improvement from baseline in the SGRQ score was 6.4 points and 7.0 points 
greater in the intravenous and subcutaneous mepolizumab groups, respectively, 
than in the placebo group (minimal clinically important change, 4 points), and 
the improvement in the ACQ-5 score was 0.42 points and 0.44 points greater in 
the two mepolizumab groups, respectively, than in the placebo group (minimal 
clinically important change, 0.5 points) (P<0.001 for all comparisons). The 
safety profile of mepolizumab was similar to that of placebo.
CONCLUSIONS: Mepolizumab administered either intravenously or subcutaneously 
significantly reduced asthma exacerbations and was associated with improvements 
in markers of asthma control. (Funded by GlaxoSmithKline; MENSA 
ClinicalTrials.gov number, NCT01691521.).