https://orcid.org/0000-0001-8639-2882
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Abstract
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.
Abbreviations
ACT, asthma control test; ADCC, antibody-dependent cellular cytotoxicity; AER, annual exacerbation rate; BEC, blood eosinophil count; BMI, body mass index; eCRF, electronic case report form; FeNO, fractional exhaled nitric oxide; GINA, Global Initiative for Asthma; ICS, inhaled corticosteroids; IgE, immunoglobulin E; IL5, interleukin 5; IL5Rα, interleukin 5 receptor alpha; IQR, interquartile range; LABA, long-acting β2-agonist; mAb, monoclonal antibody; MoA, mechanism of action; N, number of patients; NK, natural killer; OCS, oral corticosteroids; pre/post-BD FEV1, pre/post-bronchodilator forced expiratory volume in 1 second; pre/post-BD FVC, pre/post-bronchodilator-forced vital capacity; SA, severe asthma; SD, standard deviation; SEA, severe eosinophilic asthma.
Data Sharing Statement
Upon reasonable request, the corresponding author will provide the datasets used and/or analysed during the current work.
Ethics Approval and Informed Consent
The ANANKE study was carried out in agreement with the ethical standards outlined in the Declaration of Helsinki as well as laws and policies governing the Italian medical ethics and practice. Before participating in the study, each patient gave informed consent and signed updated informed consent and privacy forms related to the extended period of observation. Ethics committees/institutional review boards granted ethical approval at each site involved in the study.
Acknowledgments
EDRA SpA provided writing and editorial support, with assistance from Alessandra Rossi, PhD. We thank Claudio Marchese, Sara Rizzoli, Barbara Roncari, Alessandro Zullo, and all the members of the MediNeos team for their support during the design, management, and statistical analysis of the data.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
PC has received grants and fees as a speaker from AstraZeneca-MedImmune, Guidotti-Malesci, and GlaxoSmithKline in the last 3 years. GWC has received research grants and lecture or advisory board fees from A. Menarini, Allergy – Therapeutics, AstraZeneca-MedImmune, Boehringer Ingelheim, Chiesi, Faes, Genentech, Guidotti-Malesci, GlaxoSmithKline, HAL Allergy, Novartis, Sanofi-Aventis, Sanofi-Genzyme/Regeneron, Stallergenes-Greer, Thermo Fisher, Valeas, and Vifor Pharma in the last 3 years. SC has received grants and/or personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Glaxo Smith Kline, Guidotti, Menarini, Novartis, and Valeas. FDMa has received lecture fees at national and international meetings and consultancy fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Dompé, Guidotti/Malesci, GlaxoSmithKline, Menarini, Novartis, and Zambon. SDG has received grants and/or personal fees from AstraZeneca, Chiesi, Glaxo Smith Kline, Menarini, Novartis, and Sanofi. GP has received lecture fees and consultancy fees from AlfaSigma, AstraZeneca, Chiesi, GlaxoSmithKline, Guidotti-Malesci, Menarini, Mundipharma, Novartis, Sanofi, and Zambon; PR has been 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, and Zambon. AV has received fees as a speaker/lecturer by AstraZeneca, Chiesi Farmaceutici, GSK, Novartis, and Sanofi. MB and SB are AstraZeneca employees. FM received research funding as Principal investigator by AstraZeneca, Chiesi Farmaceutici, Novartis, and Sanofi; fees as a speaker/lecturer by AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Novartis, and Sanofi. The authors report no other conflicts of interest in this work.