ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study

Abstract

Background: Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness.

Methods: ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only.

Results: Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400-850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5-25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1-13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (- 93.3%) and to 0.06 for severe exacerbations (- 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0-10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index.

Conclusions: We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463.

Keywords: Benralizumab; Exacerbations; OCS; Real world; Severe eosinophilic asthma.

Conflict of interest statement

FM declares research fundings as Principal investigator by AstraZeneca, Chiesi Farmaceutici, Novartis, Sanofi; fees as speaker/lecturer by AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Novartis, Sanofi; EB has nothing to declare; MA has nothing to declare; PB has nothing to declare; LB has nothing to declare; MFC has nothing to declare; CC has nothing to declare; SC declares grants and/or personal fees from AstraZeneca, Boheringer Ingelheim, Chiesi, Glaxo Smith Kline, Guidotti, Menarini, Novartis, Valeas; MDA has nothing to declare; SDG received grants and/or personal fees from AstraZeneca, Chiesi, Glaxo Smith Kline, Menarini, Novartis; FDM has nothing to declare; FDM has received lectures fees at national and international meetings and consultancy fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Dompe, Guidotti/Malesci, GlaxoSmithKline, Menarini, Novartis, and Zambon; EAP has nothing to declare; GP has received lecture fees and consultancy fees from Alfasigma, AstraZeneca, Chiesi, GlaxoSmithKline, Guidotti-Malesci, Menarini, Mundipharma, Novartis, Sanofi, Zambon; PR has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini Group, Mundipharma, and Novartis, her department has received funding from Almirall, Boehringer Ingelheim, Chiesi, Novartis, and Zambon; MR declares grants and personal fees from Boehringer Ingelheim, Roche, AstraZeneca, Novartis, Chiesi, GSK, Menarini, Guidotti, AlfaSigma, Zambon; PS has nothing to declare; GS has nothing to declare; AV received payment for lectures and consultant arrangements from Novartis, GlaxoSmithKline, Teva, AstraZeneca; LS and AO are a employees of MediNeos Observational Research; SB and GV are AstraZeneca employees; EA has nothing to declare; GWC has received grant/research support from Boehringer Ingelheim, ALK, and Stallergenes, and honoraria or consultation fees from Menarini, GSK, Sanofi, Teva, Hal, AstraZeneca, and Novartis.

© 2022. The Author(s).

Figures

Fig. 1

Distribution of patients according to the number of severe exacerbations experienced in the 12 months prior to the index date. Evaluable patients with information on previous exacerbations were 196

Fig. 2

Median blood eosinophil count (cells/mm3) recorded at the index date (week 0) and during benralizumab treatment, up to week 48

Fig. 3

Data on exacerbations during benralizumab treatment. A Exacerbation occurrence. B Any exacerbation annual exacerbation rate (AER) variations C Severe exacerbation AER variations. Week 0 corresponds to the index date

Fig. 4

OCS dosage reduction during benralizumab treatment. Data are expressed as median in mg prednisone equivalent

Fig. 5

Outcome measures recorded at the index date (week 0) and during benralizumab treatment, up to week 48. A FEV1 (L); B FVC (L); C ACT score