Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study

Abstract

Background The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks. Methods ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only. Results Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430–890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: − 94.9%; severe AER: − 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: − 95.9%; severe AER: − 97.5%) and bio-experienced patients (any AER: − 92.4%; severe AER: − 94.0%). Conclusions Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients’ eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results. Trial registration: ClinicalTrials.gov Identifier: NCT04272463.

Sustained Effectiveness of Benralizumab in Naïve and Biologics-Experienced Severe Eosinophilic Asthma Patients: Results from the ANANKE Study

“…On the other hand, patients in the omalizumab group were predominantly positive for at least one allergen (57.1% of patients displayed allergen-specific IgE) and showed the highest median amount of total IgE levels (326 IU/mL, 78-520). As previously mentioned, 36,37 OCS-related comorbidities were more prevalent in bio-experienced than naïve patients, with no difference between omalizumab and mepolizumab-treated subsets (52.4% and 52.9%, respectively), despite the mepolizumab group showing the highest proportion of OCS users (41.2%) and OCS daily dose (25.0 mg, 10.0-25.0).…”

“…The ANANKE patient population eligible for extended analysis presented characteristics compatible with the late onset, eosinophilic-driven SA phenotype. 37 The key features of naïve and bio-experienced patients at index date (ie, collected during the 12 months before benralizumab initiation) have already been reported; in general, asthma clinical control appeared worse in bio-experienced patients in terms of severe AER, OCS dosage, and OCS-related comorbidities ( Table 1 ). 37 The characteristics of bio-experienced patients divided into omalizumab and mepolizumab subsets are detailed below.…”

“…We have already shown the remarkable effectiveness of benralizumab in decreasing exacerbations in naïve and bio-experienced groups. 36,37 Here, additional data are reported to describe the reduction in any and severe AER in omalizumab and mepolizumab groups after 96 weeks of treatment with benralizumab. As shown in Figure 1A, similarly to naïve and bio-experienced groups, the two switched groups had a consistent and sustained decrease in any AER, with reductions ranging from 86.2% (mepolizumab group) to 93.9% (omalizumab group) at 96 weeks.…”

“…More recently, we confirmed the durable effectiveness of benralizumab in reducing any and severe AER by more than 90% in both naïve and bio-experienced patients, up to 96 weeks of treatment. 37 …”

“…More recently, we confirmed the durable effectiveness of benralizumab in reducing any and severe AER by more than 90% in both naïve and bio-experienced patients, up to 96 weeks of treatment. 37 In light of what has been previously reported, we conducted a post hoc analysis to further describe the outcomes of long-term response to benralizumab in patients with severe eosinophilic asthma, irrespective from previous biologics treatment (naïve and bio-experienced). Moreover, bio-experienced patients were split into two subsets according to the biologic(s) previously received (omalizumab and/or mepolizumab); these were added to the comparative analysis to evaluate if and how the biologic(s) previously used influenced the response to benralizumab.…”