RATIONALE: Accumulation of eosinophils in the bronchial mucosa of individuals 
with asthma is considered to be a central event in the pathogenesis of asthma. 
In animal models, airway eosinophil recruitment and airway hyperresponsiveness 
in response to allergen challenge are reduced by specific targeting of 
interleukin-5. A previous small dose-finding study found that mepolizumab, a 
humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen 
challenge in humans.
OBJECTIVES: To investigate the effect of three intravenous infusions of 
mepolizumab, 250 or 750 mg at monthly intervals, on clinical outcome measures in 
362 patients with asthma experiencing persistent symptoms despite inhaled 
corticosteroid therapy (400-1,000 mug of beclomethasone or equivalent).
METHODS: Multicenter, randomized, double-blind, placebo-controlled study.
MEASUREMENTS AND MAIN RESULTS: Morning peak expiratory flow, forced expiratory 
volume in 1 second, daily beta(2)-agonist use, symptom scores, exacerbation 
rates, and quality of life measures. Sputum eosinophil levels were also measured 
in a subgroup of 37 individuals. Mepolizumab was associated with a significant 
reduction in blood and sputum eosinophils in both treatment groups (blood, P < 
0.001 for both doses; sputum, P = 0.006 for 250 mg and P = 0.004 for 750 mg). 
There were no statistically significant changes in any of the clinical end 
points measured. There was a nonsignificant trend for decrease in exacerbation 
rates in the mepolizumab 750-mg treatment group (P = 0.065).
CONCLUSIONS: Mepolizumab treatment does not appear to add significant clinical 
benefit in patients with asthma with persistent symptoms despite inhaled 
corticosteroid therapy. Further studies are needed to investigate the effect of 
mepolizumab on exacerbation rates, using protocols specifically tailored to 
patients with asthma with persistent airway eosinophilia.