Benralizumab reduces severe asthma exacerbations, regardless of early improvement in FEV1
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Patients with oral corticosteroid-dependent, severe eosinophilic asthma treated with benralizumab achieved greater improvements in annual exacerbation rate at 28 weeks compared with placebo, regardless of early improvement in FEV1.
Researchers reported results of a post hoc analysis of the phase 3 ZONDA trial, in which benralizumab (Fasenra, AstraZeneca) demonstrated significant and clinically relevant benefit on annual exacerbation rates vs. placebo, to evaluate the efficacy of benralizumab in patients with and without early improvements in pre-bronchodilator FEV1. The results were presented at the virtual CHEST Annual Meeting and published simultaneously in Chest.
“For oral corticosteroid (OCS)-dependent, severe asthma patients, not achieving early 200 mL and 100 mL improvement in FEV1 with benralizumab treatment does not decrease the likelihood of reducing annual exacerbation rate,” Njira L. Lugogo, MD, associate professor of internal medicine and asthma program director of the division of pulmonary and critical care medicine at University of Michigan Medicine, and colleagues wrote in the abstract.
Among patients assigned benralizumab 30 mg every 4 weeks or every 8 weeks, compared with placebo, the reduction in annual exacerbation rate was 69% (P < .05) in those who achieved FEV1 of at least 200 mL during the induction phase at week 4 before reductions in OCS dosage were attempted and 68% (P < .05) in those who achieved FEV1 of at least 100 mL. In patients who achieved FEV1 less than 200 mL and less than 100 mL at week 4, benralizumab reduced the annual exacerbation rate at week 28 by 62% (P < .05) and 67% (P < .05), respectively, compared with placebo, according to results of the post hoc analysis.
Moreover, among patients with blood eosinophil counts of at least 300 cells/µL, benralizumab reduced the annual exacerbation rate by 65% (P < .05) at week 28 in the group with FEV1 of at least 200 mL at week 4 and by 73% (P < .05) in the group with FEV1 of at least 100 mL. Again, results were similar for patients who did not achieve early clinically meaningful improvement in lung function, with a 61% (P < .05) reduction in the annual exacerbation rate at week 28 in the group with FEV1 improvement less than 200 mL at week 4 and 72% (P < .05) reduction in the group with less than 100 mL improvement, according to the abstract.
The researchers also evaluated OCS dose reduction at week 28 by FEV1 response at 4 weeks.
“Patients treated with benralizumab achieved greater reductions in OCS use compared with placebo, irrespective of FEV1 improvement, but greater reductions were seen in patients with early lung function improvement,” Lugogo said during the presentation.
Median OCS dose reduction was 91.7% at week 28 in patients assigned benralizumab with early FEV1 improvement of at least 200 mL vs. 28.6% with placebo (P < .05) and 96% at week 28 in patients with blood eosinophil counts of at least 300 cells/µL assigned benralizumab with early FEV1 improvement of at least 200 mL vs. 25% with placebo (P < .05), according to the presentation.
More patients assigned benralizumab achieved clinically meaningful improvement in lung function during the study, with FEV1 of at least 200 mL achieved by 46.4% vs. 26% at week 4 and 48.8% vs. 34.2% at end of study and FEV1 of at least 100 mL achieved by 59.4% vs. 37% at week 4 and 51.5% vs. 49.3% at end of study, according to the abstract. The researchers reported similar improvements in patients with blood eosinophil counts of at least 300 cells/µL.
Results of the main ZONDA trial were published in The New England Journal of Medicine in 2017. The trial enrolled 369 patients with severe asthma who were randomly assigned to subcutaneous benralizumab 30 mg every 4 weeks or every 8 weeks with the first three doses administered every 4 weeks or placebo for 28 weeks. Benralizumab treatment demonstrated significant and clinically relevant benefits on oral glucocorticoid use and annual exacerbation rates.