PURPOSE OF THE STUDY.
To elucidate the efficacy, safety, and patient characteristics of responsiveness to mepolizumab (a humanized monoclonal antibody against interleukin 5). Previous small, proof-of-concept studies in subjects with severe, eosinophilic asthma revealed that mepolizumab decreased exacerbation rates.
From 81 multinational centers, 621 pa-tients were enrolled. Major inclusion criteria included: age 12 to 74 years, asthma diagnosis with objective measures, ≥2 asthma exacerbations requiring oral corticosteroids in the last year, refractory asthma as defined by the American Thoracic Society criteria, and signs of eosinophilic inflammation (sputum eosinophil count ≥3%, an exhaled nitric oxide concentration ≥50 ppb, peripheral blood eosinophil count ≥0.3 × 109/L, or prompt deterioration of asthma control with inhaled or oral steroid weaning). Smokers, present or former (≥10 pack-years), were excluded.
Subjects were randomized to receive placebo or 1 of 3 doses of mepolizumab (75, 250, or 750 mg). Every 4 weeks for 13 cycles, patients received infusions. Asthma symptom scores, objective lung testing results, and blood eosinophil counts were collected at baseline and follow-up visits. The primary outcome of verified, clinically significant exacerbations during treatment and 4 weeks thereafter was defined a priori.
All mepolizumab-treated groups demonstrated a significant decrease in clinically significant exacerbations (75 mg: –48% [P < .0001]; 250 mg: –39% [P = .005]; 750 mg: –52% [P < .0001]). Visits to emergency departments and admissions also decreased; however, no significant changes in spirometry or asthma control scores were noted. No treatment-associated deaths occurred, and other potential adverse events were equivocal in the placebo and treatment groups.
Mepolizumab is generally safe and reduces exacerbation rates in select patients with asthma who have the severe, refractory, eosinophilic subtype.
Using more clinically available inclusion criteria and a larger cohort, mepolizumab provides another tool in select patients with severe, eosinophilic asthma. The study supports the clinical importance of asthma phenotyping in effectively treating asthma subjects but provides no insight for efficacy in other asthma phenotypes. The equivalent responses from the 75- and 750-mg dose might improve the cost to benefit ratio of mepolizumab depending on the manufacturer’s pricing strategy. Despite seemly optimized design and execution, all results must be viewed through a scrutinizing lens because the manufacturer participated in all aspects ranging from design to writing.
- Copyright © 2013 by the American Academy of Pediatrics