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

Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Keywords: ACT; FEV1; ORBE II; benralizumab; clinical remission; early response; real world; severe eosinophilic asthma; super-response.

Figure 1

Classification of patients with evaluable ACT and FEV₁ data according to their response during the first 120 days after initiating benralizumab. (A) The stratification of patients with available ACT data based on the observed change in ACT score achieved from baseline to 120 days under benralizumab. Based on the established criteria, patients showing an ACT score difference < 3 points were considered non-early responders (NER); patients with an ACT difference of ≥3 points, but <9 points, and a final follow-up ACT score < 24 were considered early responders (ER); and patients with an ACT difference of ≥9 points or a final follow-up ACT score ≥ 24 were considered early super-responders (ESR). (B) The distribution of patients with available data on pre-BD FEV₁ according to the response achieved from baseline to 120 days following benralizumab initiation in terms of pre-BD FEV₁ gain (mL). Based on the pre-specified criteria, patients were classified as follows: NER, when the pre-BD FEV₁ difference between baseline and the highest follow-up value was ≤100 mL; ER when the pre-BD FEV₁ difference was ≥100 mL but <230 mL; and ESR when the pre-BD FEV₁ difference was ≥230 mL. ACT, asthma control test; BD, bronchodilator; FEV₁, forced expiratory volume in 1 s.

Figure 2

Temporal dynamics of ACT score and pre-BD FEV₁ change during benralizumab treatment in patient subgroups. (A) Trajectory of ACT scores over a 12-month period in ACT scores discriminating between ACT-ESR patients (n = 20) and those who did not achieve an ACT early super-response (NER + ER; n = 20). (B) The graph plots pre-BD FEV₁ changes over a 12-month period, discriminating between FEV₁-ESR patients (n = 38) and those who did not achieve an FEV₁ early super-response (NER + ER; n = 27)). Each line represents an individual patient. The dashed red lines represent the following clinically relevant thresholds: an ACT score of 20 (Panel A) and a pre-BD FEV₁ increment of 230 mL (Panel B). ACT, asthma control test; BD, bronchodilator; FEV₁, forced expiratory volume in 1 s; NER, non-early responders; ER, early responders; ESR, early super-responders.

Figure 3

Attainment of clinical outcomes after 1-year follow-up with benralizumab treatment. (A) Proportion of patients who met pre-defined clinical objectives in response to benralizumab in the ACT-TP and ACT-ESR subgroups (left graph) and in the FEV₁-TP and FEV₁-ESR subgroups (right graph). (B) The Venn diagrams show the number of ESR achieving one or more of the four clinical objectives (zero exacerbations, no use of mOCS, ACT score ≥ 20, and pre-BD FEV₁ increment ≥100 mL). The left diagram represents the ACT-ESR subgroup, while the right diagram represents the FEV₁-ESR group. The tables below each diagram show the proportion of patients that achieved super-response and clinical remission. Percentages were calculated based on the number of patients within each subgroup who had available data for the parameter or a combination of parameters under analysis (N). The count of patients who reached each clinical goal or response threshold to benralizumab is indicated as “n”. ACT, asthma control test; BD, bronchodilator; BEC, blood eosinophil count; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 s; mOCS, maintenance oral corticosteroids; ppb, parts per billion; ESR, early super-responders; TP, total population.