Benralizumab may help oral corticosteroid-sparing in severe asthma
Benralizumab helps reduce the need for oral corticosteroids by over four folds while maintaining asthma control in adults with severe eosinophilic asthma compared with placebo, according to the ZONDA* study presented at the ATS Conference 2017 in Washington, DC, US.
Patients treated with benralizumab (30 mg Q4W or Q8W) had their oral glucocorticoid doses significantly reduced by 75 percent from baseline at week 28 compared with a 25 percent reduction in those receiving placebo (p<0.001). [N Engl J Med 2017;doi:10.1056/NEJMoa1703501]
Also, more than half of the eligible patients (using prednisone at ≤12.5 mg/day) who were treated with benralizumab were able to stop taking oral glucocorticoid completely at week 28 (56 percent and 52 percent, vs 19 percent for benralizumab Q4W and Q8W, respectively, vs placebo; p<0.001 and p=0.002 for each comparison).
“Reductions in the oral glucocorticoid dose were observed regardless of the baseline oral glucocorticoid dose,” observed the researchers.
They found that benralizumab-treated patients were at least four times more likely to reduce oral glucocorticoid dose than placebo controls (odds ratio [OR], 4.09 and 4.12 for benralizumab Q4W and Q8W, respectively, vs placebo; p<0.001 for both comparisons).
There were also more patients in the benralizumab group who achieved a ≥90 percent dose reduction from baseline in oral glucocorticoid dose at week 28 compared with the placebo group (33 percent and 37 percent, vs 12 percent for benralizumab Q4W and Q8W, respectively, vs placebo).
Despite less corticosteroid use, annual exacerbation rate was 55 percent lower with benralizumab Q4W (p=0.003) and 70 percent lower with benralizumab Q8W than with placebo (p<0.001). FEV1** was also comparable among the three treatment arms by week 28.
The multicentre, double-blind, parallel-group phase III trial randomized 220 patients with severe eosinophilic asthma who relied on oral glucocorticoids (in addition to high-dose inhaled corticosteroids and LABA***) for asthma control in a 1:1:1 ratio to receive either subcutaneous benralizumab 30 mg given at QW4 or QW8 (with first three doses at every 4 weeks), or placebo for 28 weeks.
Adverse events occurred at similar rates among all groups, with the most common events being nasopharyngitis (17 percent of the total population), worsening asthma (13 percent), and bronchitis (10 percent). Serious adverse events were reported in 10 percent of each of the benralizumab Q4W and Q8W arms vs 19 percent in the placebo group, with worsening asthma occurring most commonly.
“Benralizumab is a humanized ... monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor … [and depletes] eosinophils by means of natural killer cell–mediated antibody-dependent cellular cytotoxic effects,” said the researchers.
However, in 20 percent of the patients who did not respond to benralizumab (in terms of oral glucocorticoid dose reduction), the researchers found that their baseline blood eosinophil counts were similar to those who had the greatest dose reduction with the drug.
“Future studies may aim to investigate the characteristics of patients that are indicative of a response to benralizumab, to assess the long-term safety and efficacy of eosinophil depletion,” they suggested.