A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma

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-findingstudy foundthatmepolizumab, 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 μg 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 β2-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 associatedwith a significant reduction in blood and sputum eosinophils in both treatment groups (blood, P < 0.001 for both doses; sputum, P = 0.006 for 250mg and P = 0.004 for 750mg). 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 themepolizumab 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.