Blood Eosinophil Count and Fractional Exhaled Nitric Oxide as a Combined Predictor of Treatment Response to Benralizumab for Patients with Severe, Eosinophilic Asthma

Purpose: In a Phase II b RCT in severe, eosinophilic asthma, benralizumab (20 mg or 100 mg every 8 weeks [with the first three doses every 4 weeks] for 1 year) reduced asthma exacerbation rate (AER) for adults with blood eosinophil counts (BEC) ≥ 300 cells/µL. Data suggest that fractional exhaled nitric oxide (FeNO) correlates with eosinophilic inflammation. In addition, along with BEC, FeNO may provide prognostic information for a more complete assessment of treatment response to biological medication in patients with severe asthma. To further understand the possible additive prognostic value of FeNO, we compared treatment for subgroups of severe eosinophilic asthma patients with high and low baseline FeNO measurements.

Methods: We conducted post-hoc analyses of a treatment effect for subgroups of asthma patients with BEC ≥ 300 cells/µL (eosinophilic patients) receiving benralizumab (combined 20 mg and 100 mg groups) or placebo with high- (≥ 25 ppb) or low-FeNO (< 25 ppb) measurements. Treatment effects were assessed through modelled AER and change from baseline in lung function (FEV₁) for the high- and low-FeNO groups.

Results: Eosinophilic patients with high FeNO (n = 136) had a greater median baseline BEC (536 cells/µL) compared with eosinophilic patients with low FeNO (n = 114 [400 cells/µL]). Benralizumab reduced AER by 58% compared with placebo (0.30 for benralizumab vs. 0.72 for placebo, nominal p < 0.0424) for eosinophilic patients with high FeNO and by 41% compared with placebo (0.36 for benralizumab vs. 0.61 for placebo, nominal p = 0.1074) for eosinophilic patients with low FeNO. Eosinophilic patients with either high or low FeNO treated with benralizumab improved pre-bronchodilator FEV₁ at Week 52 compared with placebo (210 mL, nominal p = 0.0349; 150 mL, nominal p = 0.065; respectively).

Conclusions: Eosinophilic patients with high-FeNO measurements had greater baseline BEC than patients with low-FeNO measurements. Although the response in AER and FEV₁ was numerically greater for eosinophilic patients with high FeNO, benralizumab reduced AER and improved lung function regardless of FeNO at baseline. These post-hoc analyses suggest that FeNO may provide limited additional prognostic information for patients with severe, eosinophilic asthma.

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Artikel online veröffentlicht:
30. April 2021