ORBE II Study: Clinical Characteristics and Outcomes After Treatment with Benralizumab According to Airflow Obstruction Status and Smoking Habit.

Background/Objectives: Evidence on the use of biologics in severe eosinophilic asthma (SEA) associated with persistent airflow obstruction (PAO) status and smoking habits is scarce. As these factors could potentially impact real-world benralizumab clinical effects, this study was conceived to provide a deeper understanding of these specific patient subgroups. Methods: This observational, retrospective ORBE II study (NCT04648839) involved 204 adults with uncontrolled SEA treated with benralizumab in Spain. In this analysis, patients were categorized by baseline PAO status (PAO- or PAO+) and smoking habit (SMK- or SMK+) to assess baseline characteristics and clinical outcomes after one year of follow-up. The impact of smoking on PAO+ patients was also analyzed. Results: This analysis showed that 75.6% of patients had PAO and 36.9% were former/current smokers. After benralizumab, both PAO subgroups showed substantial improvement, with higher proportions of PAO+ patients achieving prespecified clinical objectives. Benralizumab benefited patients regardless of their smoking habit, though patients who had never smoked exhibited slightly fewer exacerbations, greater improvements in ACT scores, and a higher proportion achieved a ≥100 mL increase in pre-BD FEV1. An analysis of the impact of smoking on the PAO+ subgroup showed that while a similar proportion of patients were able to eliminate exacerbations and discontinue OCS use, higher percentages of PAO+SMK- patients achieved an ACT score ≥ 20 and a ≥100 mL increase in pre-BD FEV1. Conclusions: PAO is common among patients included in ORBE II, and a considerable proportion are former/current smokers. This study showed that clinical outcomes improved after benralizumab initiation regardless of these factors, highlighting its potential as a valuable therapeutic option for managing SEA. These findings also emphasize the need for further real-world evidence to optimize treatment strategies for diverse patient subgroups.