The Relationship Between Severe Asthma Eosinophilic Phenotypes and the Clinical Response to Benralizumab at 16 Weeks

Introduction: Benralizumab is a monoclonal antibody against IL-5R and is licensed for the treatment of severe eosinophilic asthma (SEA). It is appreciated that there are sub-phenotypes of SEA relating to both atopy and age of onset. However, whether a differential response to benralizumab relating to these phenotypes exists and is evident at 16 weeks – the first time-point when asthma biologic efficacy is conventionally assessed - is unknown. Methods: A retrospective review of SEA patients treated with benralizumab at Guy’s Severe Asthma Centre, UK was performed. All subjects who had completed 16 weeks treatment were included in this analysis. SEA subjects were divided into 3 sub-phenotypes: child-onset atopic (CA), adult-onset atopic (AA) and adult-onset non-atopic (ANA). Results: 80 patients who had received ≥16 weeks of benralizumab were identified including 39 CA, 24 AA and 17 ANA patients. At baseline there were no significant differences between ACQ-6, AQLQ, FEV1, previous exacerbation frequency or maximal eosinophil count. At 16 weeks, 26/39 (67%) of CA patients remained exacerbation free. This was significantly lower than the 22/24 (92%) AA (p=0.03) and 17/17 (100%) ANA patients (p=0.006). There were significant improvements in both ACQ-6 and AQLQ (p<0.01) but no significant differences between groups. Conclusion: Following 16 weeks of benralizumab, some differences in efficacy are already apparent between sub-phenotypes of SEA. Patients with adult-onset atopic and non-atopic SEA are more likely to be exacerbation-free at 16 weeks compared to child-onset atopic SEA despite a similar background exacerbation rate and eosinophil count.