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

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.

Purpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics. Patients and Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used. Results: A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively). Conclusion: Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.