RATIONALE: There is a need to characterize the real-world impact of benralizumab, an anti-interleukin-5 receptor alpha antibody, for add-on maintenance therapy of patients with severe eosinophilic asthma. The objective of this study was to assess change in patient-reported outcomes following initiation of benralizumab, focusing on asthma control, quality of life (QoL), and work and activity impairment. This is an interim analysis of the prospective, single-arm, multi-center, observational POWER study. Eligible patients were recruited from 20 clinics across Canada from 2019 to 2022, had an Asthma Control Questionnaire, 6 Item (ACQ-6) score ≥1.5 and were benralizumab-naïve. MEASUREMENTS AND MAIN RESULTS: A total of 131 patients had baseline assessments at the 24-week interim analysis. Asthma control was assessed with ACQ-6 (minimum clinically important difference: change of 0.5 units), and stratified into well-controlled (<0.75), partial control (0.75–1.5) and poor control (>1.5). Improvements in asthma control were observed as early as one week following benralizumab initiation. At 24 weeks, mean change in ACQ-6 was −1.46 (95% confidence interval: −1.71, −1.21), and 47% achieved well-controlled or partial control. Mean EuroQol 5 Dimension, 5 Level (EQ-5D-5L) utility score increased nearly 10% from baseline (0.09; standard deviation 0.2). Absenteeism and presenteeism decreased from baseline (20% and 39%, respectively) to 24 weeks (2% and 21%, respectively). Patients reported meaningful improvements in asthma control, quality of life (QoL) and work and activity impairment 24 weeks after initiating benralizumab, highlighting its positive impact in patients with severe asthma. One- and two-year follow-up are planned to assess exacerbations, healthcare resource use and sustainability of observed benefits.