Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial

摘要: Summary Background Eosinophilia is associated with worsening asthma severity and decreased lung function, increased exacerbation frequency. We assessed the safety efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor α that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, for patients severe, uncontrolled eosinophilia. Methods did randomised, double-blind, parallel-group, placebo-controlled phase 3 study at 374 sites in 17 countries. recruited (aged 12–75 years) physician-based diagnosis least 1 year two exacerbations while on high-dosage inhaled corticosteroids long-acting β 2 -agonists (ICS plus LABA) previous year. Patients were randomly assigned (1:1:1) an interactive web-based voice response system to benralizumab 30 mg either every 4 weeks (Q4W) or 8 (Q8W; first three doses weeks) placebo Q4W 48 as add their standard treatment. stratified 2:1 according blood eosinophil counts 300 cells per μL less than μL. All investigators involved patient treatment clinical assessment masked allocation. The primary endpoint was annual rate ratio versus placebo, key secondary endpoints prebronchodilator forced expiratory volume s (FEV ) total symptom score week 48, Efficacy analyses intention treat (based full analysis set); included drug received. This registered ClinicalTrials.gov, number NCT01928771. Findings Between Sept 19, 2013, March 16, 2015, 2681 enrolled, 1205 whom met criteria assigned: 407 400 Q4W, 398 Q8W. 267 group, 275 Q8W group had population. Compared reduced over when given (rate 0·55, 95% CI 0·42–0·71; p compared (least-squares mean change from baseline: 0·106 L, 0·016–0·196; 0·159 0·068–0·249). symptoms improved regimen difference −0·25, −0·45 −0·06), but not (−0·08, −0·27 0·12). most common adverse events (105 [13%] 797 benralizumab-treated vs 78 [19%] placebo-treated patients) nasopharyngitis (93 [12%] 47 [12%]). Interpretation These results confirm severe elevated eosinophils, which are ICS LABA, provide support be additional option this disease Funding AstraZeneca Kyowa Hakko Kirin.