Use of CompEx in eosinophilic patients with severe, uncontrolled asthma on benralizumab.

Abstract

CompEx Asthma, a composite end-point for asthma exacerbations, captures clinically relevant, diary-based acute worsening events (AWEs) (defined as deterioration in daily peak expiratory flow concurrent with deterioration in asthma symptoms and/or rescue therapy use) and severe exacerbations (SevEx) (defined by American Thoracic Society/European Respiratory Society guidelines). We hypothesised that CompEx and SevEx would show similar benralizumab treatment effects and correlations to blood eosinophil counts in patients with severe asthma. This post hoc analysis of pooled 12-month data from two phase 3 studies included patients aged ≥16 years with severe, uncontrolled asthma who were randomised to benralizumab 30 mg or placebo. Annualised event rates were analysed using a negative binomial model. The impact of blood eosinophil count on treatment effect was assessed. Among patients with a blood eosinophil count ≥300 cells·µL-1 (n=913), benralizumab reduced the annualised event rate versus placebo for CompEx (1.57 versus 2.57; risk ratio 0.61, 95% CI 0.53-0.70, p<0.001), SevEx (0.94 versus 1.55; risk ratio 0.60, 95% CI 0.52-0.70, p<0.001) and AWE (0.92 versus 1.57; risk ratio 0.59, 95% CI 0.48-0.72, p<0.001), with greater treatment effects observed for higher blood eosinophil counts. In patients with blood eosinophil count ≥300 cells·µL-1, benralizumab was associated with shorter median event duration (CompEx: 10.5 days versus 17.0 days; SevEx: 10.0 days versus 15.0 days; AWE: 5.0 days versus 6.0 days). Benralizumab reduced the risk of CompEx events with treatment effects similar to those for SevEx and AWEs across a range of blood eosinophil counts. Use of CompEx supports the evaluation of benralizumab and other novel drugs in clinical studies.