• Alexander G Mathioudakis, Sebastian Bate, Pradeesh Sivapalan, Stæhr JensenJens-UlrikJUDepartment of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, C, Dave Singh, and Jørgen Vestbo.
• Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, England; North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, England. Electronic address: Alexander.Mathioudakis@Manchester.ac.uk.
• Chest. 2024 Jul 9.

BackgroundThe varied treatment response to inhaled corticosteroids (ICS) in COPD and the increased risk of pneumonia necessitate a personalized ICS therapeutic approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. However, BEC appears to change in response to ICS treatment.Research QuestionDoes BEC measured on or off ICS treatment, or the change in BEC during ICS treatment, best predict treatment response to ICS in COPD?Study Design And MethodsFLAME, a 52-week, double-blind randomized controlled trial compared long-acting beta-2 agonist (LABA)/long-acting muscarinic antagonist (LAMA) with LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing pre-run-in and post-run-in period BEC to represent BEC on and off ICS, respectively. In this post hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS-containing regimen.ResultsOur study confirms that LABA/LAMA combination is superior, or at least noninferior, to LABA/ICS in curbing exacerbations for most FLAME participants. However, higher BEC off ICS and BEC on ICS and significant BEC suppression during ICS treatment corresponded to superior response to LABA/ICS in terms of exacerbation rate, time to first exacerbation, and time to first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment (≥ 200 cells/μL), and higher BEC on ICS did not predict ICS treatment response. For these patients, BEC off ICS and BEC change proved more predictive. Excess pneumonia risk associated with ICS appeared to be confined to patients who do not benefit from this treatment. BEC was not predictive of treatment effects on lung function and health status.InterpretationThis exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response.Trial RegistrationClinicalTrials.gov; No.: NCT01782326; URL: www.Clinicaltrialsgov.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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