S137 Benralizumab is effective at reducing airway inflammation in severe asthma patients following non-response to mepolizumab associated with persistent sputum eosinophilia

Abstract

<h3>Background</h3> Anti-IL-5 monoclonal antibodies reduce systemic corticosteroid use, exacerbation rate, and airway inflammation in severe asthma. Different effectors of the eosinophil IL-5 pathway are targeted, but algorithms to choose the most appropriate biologic for each patient are still being refined. Our team regularly monitors severe asthma patients’ airway inflammation using sputum eosinophils. <h3>Aims</h3> To investigate clinical outcomes of patients that switched to benralizumab after non-response to mepolizumab associated with persistent sputum eosinophilia. <h3>Methods</h3> We prospectively monitored sputum cell counts of patients starting MDT-approved benralizumab after: failing to respond to mepolizumab, and whose positive sputum eosinophils remained above the threshold of 3%. Additional clinical parameters were recorded including corticosteroid dose, ACQ, AQLQ, and blood eosinophils. Lung function testing was severely impacted by the COVID pandemic. <h3>Results</h3> Fifty-one of 183 (27.9%) mepolizumab patients to date have been identified as candidates for a switch of therapy with residual positive sputum eosinophils, of which 44 have received their first doses of benralizumab and 16 have completed 6 months of treatment with available sputum eosinophil results. After 6 months on benralizumab therapy, clinically and statistically significant improvements in ACQ and mAQLQ were observed compared to baseline. All but two patients had negative sputum eosinophils (&lt; 3%) compared to levels on mepolizumab (<b>Table</b>). Both also had elevated blood eosinophils: one patient was sampled during an exacerbation, the other is being investigated for parasitic infestation due to frequent foreign travels. At baseline 81% of patients were taking maintenance oral corticosteroids compared to 44% at 6 months (NS). <h3>Conclusions</h3> More than a quarter of patients failed to respond to mepolizumab and displayed persistent airway eosinophilia. Of these, 88% achieved negative airway inflammation on benralizumab with significant clinical improvement (ACQ, AQLQ) and clinically (though not statistically on this small sample size) significant fall of OCS. Benralizumab appears to prove effective at reducing inflammation at tissue level in patients previously unable to achieve this on a different anti-IL-5 therapy. As more patients progress through their treatment, repeat monitoring at 12 months will establish if this benefit is maintained and is associated with long term steroid dose reduction, and exacerbation rate.