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.