BACKGROUND: Many patients with severe asthma rely on oral glucocorticoids to 
manage their disease. We investigated whether benralizumab, a monoclonal 
antibody directed against the alpha subunit of the interleukin-5 receptor that 
significantly reduces the incidence of asthma exacerbations, was also effective 
as an oral glucocorticoid-sparing therapy in patients relying on oral 
glucocorticoids to manage severe asthma associated with eosinophilia.
METHODS: In a 28-week randomized, controlled trial, we assessed the effects of 
benralizumab (at a dose of 30 mg administered subcutaneously either every 4 
weeks or every 8 weeks [with the first three doses administered every 4 weeks]) 
versus placebo on the reduction in the oral glucocorticoid dose while asthma 
control was maintained in adult patients with severe asthma. The primary end 
point was the percentage change in the oral glucocorticoid dose from baseline to 
week 28. Annual asthma exacerbation rates, lung function, symptoms, and safety 
were assessed.
RESULTS: Of 369 patients enrolled, 220 underwent randomization and started 
receiving benralizumab or placebo. The two benralizumab dosing regimens 
significantly reduced the median final oral glucocorticoid doses from baseline 
by 75%, as compared with a reduction of 25% in the oral glucocorticoid doses in 
the placebo group (P<0.001 for both comparisons). The odds of a reduction in the 
oral glucocorticoid dose were more than 4 times as high with benralizumab as 
with placebo. Among the secondary outcomes, benralizumab administered every 4 
weeks resulted in an annual exacerbation rate that was 55% lower than the rate 
with placebo (marginal rate, 0.83 vs. 1.83, P=0.003), and benralizumab 
administered every 8 weeks resulted in an annual exacerbation rate that was 70% 
lower than the rate with placebo (marginal rate, 0.54 vs. 1.83, P<0.001). At 28 
weeks, there was no significant effect of either benralizumab regimen on the 
forced expiratory volume in 1 second (FEV1), as compared with placebo. The 
effects on various measures of asthma symptoms were mixed, with some showing 
significant changes in favor of benralizumab and others not showing significant 
changes. Frequencies of adverse events were similar between each benralizumab 
group and the placebo group.
CONCLUSIONS: Benralizumab showed significant, clinically relevant benefits, as 
compared with placebo, on oral glucocorticoid use and exacerbation rates. These 
effects occurred without a sustained effect on the FEV1. (Funded by AstraZeneca; 
ZONDA ClinicalTrials.gov number, NCT02075255 .).