Benralizumab attenuates blood and airway eosinophilia in severe asthmatics with inadequate response to anti-IL-5 neutralizing antibodies

<b>Introduction:</b> Targeting the IL-5 ligand does not suppress airway eosinophilia in a subset of severe asthmatics. We investigated if targeting the IL-5 receptor with benralizumab would suppress airway eosinophilia leading to greater asthma control. <b>Methods:</b> Sixteen severe asthmatics (9 females, mean age 58±14 years) on daily high-dose corticosteroid therapy (14 prednisone-dependent, median dose 7.5 mg) with ACQ≥1.5 and sputum eosinophils&gt;3% despite mepolizumab (n=13, 100 mg, subcutaneous) or Reslizumab (n=3, 3mg/kg, intravenous) for ≥6 months were recruited in a sequential placebo-controlled trial (NCT03470311). Clinical outcomes were assessed at baseline (V1), after two months of placebo treatment (V3), and after 5 injections of benralizumab (V10). <b>Results:</b> Benralizumab completely depleted sputum and blood eosinophils in all 16 patients, with clinical improvements in FEV₁, and ACQ-5 (Fig1). However, the decrease in fractional exhaled nitric oxide, FeNO (p&gt;0.05) was modest. Despite complete suppression of eosinophilia and mean decrease in asthma control questionnaire (ACQ-5) by 1.21 points, 37% (6/16) patients still documented ACQ &gt;1.5. <b>Conclusions:</b> Targeting IL-5R with benralizumab suppresses sputum and blood eosinophilia that is uncontrolled by anti-IL5 neutralizing antibodies in severe asthmatics. Residual symptoms, associated with raised FeNO may indicate IL-4R activity.