Benralizumab impact on asthma exacerbation greater with higher eosinophilic count, frequent exacerbation history
The anti-eosinophilic monoclonal antibody benralizumab improved annual exacerbation rates (AER) in patients with severe, uncontrolled asthma, with the improvement more pronounced with increasing baseline blood eosinophil levels and a history of more frequent exacerbations, pooled analysis of the phase III SIROCCO* and CALIMA** trials showed.
“Patients with a combination of greater baseline blood eosinophil counts and a history of more frequent exacerbations achieved the greatest benefit,” said the researchers.
“[E]xacerbation history could be used to identify patients who would potentially be responsive to benralizumab, with patients with a history of more frequent exacerbations achieving greater benefit,” they said.
Patients with severe, uncontrolled asthma with a history of exacerbations and receiving high-dose inhaled corticosteroids and long-acting β2 agonists (LABA) for ≥12 months prior were randomized to receive subcutaneous benralizumab (30 mg, Q4W [n=756] or Q8W with the first three doses given Q4W [n=762]) or placebo Q4W (n=777) for 48 (SIROCCO, mean age 48.8 years, 66 percent female) or 56 weeks (CALIMA, mean age 50.2 years, 62 percent female).
Patients who had baseline blood eosinophil counts of ≥0 cells/µL and received benralizumab had lower AER than those who received placebo (0.73 and 0.75 for benralizumab Q4W and Q8W, respectively, vs 1.16 for placebo; rate ratio [RR], 0.63, 95 percent confidence interval [CI], 0.54–0.74 and RR, 0.64, 95 percent CI, 0.55–0.75 for benralizumab Q4W and Q8W, respectively; p<0.0001 for each comparison). [Lancet Respir Med 2017;doi:10.1016/S2213-2600(17)30344-2; ERS 2017, abstract OA2902]
The effects of benralizumab on AER improvement were more evident with increasing blood eosinophil counts in patients on benralizumab Q4W and Q8W (RR, 0.61 and 0.63 [≥150 cells/µL], RR, 0.59 and 0.57 [≥300 cells/µL], and RR, 0.59 and 0.50 [≥450 cells/µL]; p<0.0001 for all comparisons vs placebo).
In patients with blood eosinophil counts of ≥300 cells/µL, patients with ≥3 exacerbations in the year prior had better AER improvements than those with two exacerbations, regardless of benralizumab dosing schedule (≥3 exacerbations; RR, 0.55 [benralizumab Q4W] and 0.45 [benralizumab Q8W]; p<0.0001 for each comparison vs placebo; two exacerbations; RR, 0.65; p=0.0016 [benralizumab Q4W] and RR, 0.73; p=0.0194 [benralizumab Q8W]).
Patients on benralizumab with blood eosinophil counts of ≥0 cells/µL also had improved prebronchodilator forced expiratory volume in the first second (FEV1) compared with those on placebo at treatment end (difference in least squares mean change from baseline, 0.072 L; p=0.0038 and 0.099 L; p<0.0001 for benralizumab Q4W and Q8W, respectively), with improvement increasing with baseline blood eosinophil count.
Previous studies have indicated that blood eosinophil count alone is not a sufficient biomarker to detect eosinophilic airway inflammation. [J Allergy Clin Immunol 2013;132:72-80; Allergy 2013;68:402-406]
“Our findings illustrate the limitations of clinicians’ and regulatory agencies’ use of only blood eosinophil counts [≥300 cells/µL] to identify patients with eosinophilic inflammation,” said the researchers. “In the consideration of treatment options, other factors, including clinical characteristics such as exacerbation history, should be factored in alongside blood eosinophil counts,” they said.
“[I]dentification of treatable traits would be the basis for future development of precision medicine for airways diseases,” said Professor Marc Humbert from Université Paris-Sud, Paris, France, in a commentary. [Lancet Respir Med 2017;doi:10.1016/S2213-2600(17)30343-0]
“Well-defined predictors of improved response to benralizumab will be of great interest to support precision medicine in severe asthma,” he said.