BACKGROUND: Many patients with severe asthma require regular treatment with oral 
glucocorticoids despite the use of high-dose inhaled therapy. However, the 
regular use of systemic glucocorticoids can result in serious and often 
irreversible adverse effects. Mepolizumab, a humanized monoclonal antibody that 
binds to and inactivates interleukin-5, has been shown to reduce asthma 
exacerbations in patients with severe eosinophilic asthma.
METHODS: In a randomized, double-blind trial involving 135 patients with severe 
eosinophilic asthma, we compared the glucocorticoid-sparing effect of 
mepolizumab (at a dose of 100 mg) with that of placebo administered 
subcutaneously every 4 weeks for 20 weeks. The primary outcome was the degree of 
reduction in the glucocorticoid dose (90 to 100% reduction, 75 to less than 90% 
reduction, 50 to less than 75% reduction, more than 0 to less than 50% 
reduction, or no decrease in oral glucocorticoid dose, a lack of asthma control 
during weeks 20 to 24, or withdrawal from treatment). Other outcomes included 
the rate of asthma exacerbations, asthma control, and safety.
RESULTS: The likelihood of a reduction in the glucocorticoid-dose stratum was 
2.39 times greater in the mepolizumab group than in the placebo group (95% 
confidence interval, 1.25 to 4.56; P=0.008). The median percentage reduction 
from baseline in the glucocorticoid dose was 50% in the mepolizumab group, as 
compared with no reduction in the placebo group (P=0.007). Despite receiving a 
reduced glucocorticoid dose, patients in the mepolizumab group, as compared with 
those in the placebo group, had a relative reduction of 32% in the annualized 
rate of exacerbations (1.44 vs. 2.12, P=0.04) and a reduction of 0.52 points 
with respect to asthma symptoms (P=0.004), as measured on the Asthma Control 
Questionnaire 5 (in which the minimal clinically important difference is 0.5 
points). The safety profile of mepolizumab was similar to that of placebo.
CONCLUSIONS: In patients requiring daily oral glucocorticoid therapy to maintain 
asthma control, mepolizumab had a significant glucocorticoid-sparing effect, 
reduced exacerbations, and improved control of asthma symptoms. (Funded by 
GlaxoSmithKline; SIRIUS ClinicalTrials.gov number, NCT01691508.).