Early and Sustained Clinical Benefits of Benralizumab in Severe Eosinophilic Asthma: Findings from the ORBE II Study

<b>Introduction:</b> Benralizumab has demonstrated rapid efficacy in treating severe eosinophilic asthma (SEA). This study aims to characterize early responses to benralizumab, the patient features observed in those with early responses, and the potential patient features that could predict them, and it also evaluates whether these improvements are sustained during a one-year follow-up (FUP) in clinical practice. <b>Methods:</b> This analysis was conducted using the ORBE II study database. ORBE II is an observational, retrospective study that included uncontrolled SEA adult patients treated with benralizumab according to routine clinical practice in Spain. We analysed patients with available data on the asthma control test (ACT) at baseline and within the first 120 days after benralizumab initiation, identifying ACT "Early Super-Responders" (ACT-ESR) as patients with a ≥9 point-improvement in the ACT score or reaching an absolute score of ≥24. Likewise, we assessed patients with available data on the pre-BD FEV₁ during the same study periods, defining those with a pre-BD FEV₁ increment of ≥230 mL as FEV₁-ESR patients. Clinical outcomes were described up to 1 year of FUP. <b>Results:</b> A total of 45 and 65 patients with data for ACT and FEV₁, respectively, during the first 120 days of treatment were analysed. Of those, 55.5% and 58.5% of patients were categorized as ACT-ESR and FEV₁-ESR, respectively. At baseline, both groups showed high T2 inflammation markers and a high prevalence of comorbidities (chronic rhinosinusitis with nasal polyposis: 56% and 50%; gastro-oesophageal reflux disease: 24% and 40%, respectively). Poor asthma control (ACT < 20) was observed at baseline in 96% of ACT-ESR, while impaired lung function (pre-BD FEV₁ < 80%) was present in 71.7% of FEV₁-ESR. Oral corticosteroid (OCS) dependency affected 25% and 30% of ACT-ESR and FEV₁-ESR, respectively. The early gains observed in ACT-ESR and FEV₁-ESR were sustained up to 1 year of FUP, with 90.5% and 66.7% of patients achieving a super-response (zero exacerbations and no OCS use) and 92.0% and 71.1% meeting clinical remission criteria (zero exacerbations, no OCS use, ACT ≥ 20 and pre-BD FEV₁ increment of ≥100 mL), respectively. <b>Conclusions:</b> Benralizumab provides early benefits for SEA patients in clinical practice, with more than half achieving early super-responses in both ACT score and lung function. These improvements were sustained over a 1-year FUP, resulting in high rates of clinical remission.