Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies

Abstract

Background: Benralizumab is an anti-eosinophilic, anti-interleukin-5 receptor α monoclonal antibody that has been shown to significantly reduce asthma exacerbations and improve lung function for patients with severe, uncontrolled asthma. We further explored the efficacy of benralizumab for patients with different baseline blood eosinophil thresholds and exacerbation histories.

Methods: This study is a pooled analysis of the results from the randomised, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase 3 studies. In these studies, patients with severe, uncontrolled asthma were randomly assigned (1:1:1) to receive subcutaneous benralizumab 30 mg, either every 4 weeks or every 8 weeks (with first three doses given every 4 weeks), or placebo every 4 weeks. The primary endpoint was annual exacerbation rate (AER) ratio versus placebo, analysed by baseline eosinophil counts (≥0, ≥150, ≥300, or ≥450 cells per μL) and by number of exacerbations (two vs three or more) during the year before enrolment. The analyses were done in accordance with the intention-to-treat principle.

Findings: Of 2295 patients, 756 received benralizumab every 4 weeks, 762 received benralizumab every 8 weeks, and 777 patients received placebo. AER among patients with baseline blood eosinophil counts of at least 0 cells per μL was 1·16 (95% CI 1·05-1·28) in patients who received placebo versus 0·75 (0·66-0·84) in patients who received benralizumab every 8 weeks (rate ratio 0·64, 0·55-0·75; p<0·0001). In patients who received benralizumab every 4 weeks who had eosinophil counts of 0 or more cells per μL, AER was 0·73 (0·65-0·82); rate ratio versus placebo was 0·63 (0·54-0·74; p<0·0001). The extent to which exacerbation rates were reduced increased with increasing blood eosinophil thresholds and with greater exacerbation history in patients in the 4-weekly and 8-weekly benralizumab groups. Greater improvements in AER were seen with benralizumab compared with placebo for patients with a combination of high blood eosinophil thresholds and a history of more frequent exacerbations.

Interpretation: These results will help to guide clinicians when they are deciding whether to use benralizumab to treat patients with severe, uncontrolled, eosinophilic asthma.

Funding: AstraZeneca.