Blood eosinophils to guide inhaled maintenance therapy in a primary care COPD population.

Helen F Ashdown,Ian D Pavord,Mona Bafadhel,Emily Mcfadden,Margaret Smith,Chris C Butler

doi:10.1183/23120541.00606-2021

Helen F Ashdown, Ian D Pavord + Show 4 more

Open Access

https://doi.org/10.1183/23120541.00606-2021

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Abstract

Blood eosinophils are a potentially useful biomarker for guiding inhaled corticosteroid (ICS) treatment decisions in COPD. We investigated whether existing blood eosinophil counts predict benefit from initiation of ICS compared to bronchodilator therapy.We used routinely collected data from UK primary care in the Clinical Practice Research Datalink. Participants were aged ≥40 years with COPD, were ICS-naïve and starting a new inhaled maintenance medication (intervention group: ICS; comparator group: long-acting bronchodilator, non-ICS). Primary outcome was time to first exacerbation, compared between ICS and non-ICS groups, stratified by blood eosinophils (“high” ≥150 cells·µL−1 and “low” <150 cells·µL−1).Out of 9475 eligible patients, 53.9% initiated ICS and 46.1% non-ICS treatment with no difference in eosinophils between treatment groups (p=0.71). Exacerbation risk was higher in patients prescribed ICS than those prescribed non-ICS treatment, but with a lower risk in those with high eosinophils (hazard ratio (HR) 1.04, 95% CI 0.98–1.10) than low eosinophils (HR 1.19, 95% CI 1.09–1.31) (p-value for interaction 0.01). Risk of pneumonia hospitalisation with ICS was greatest in those with low eosinophils (HR 1.26, 95% CI 1.05–1.50; p-value for interaction 0.04). Results were similar whether the most recent blood eosinophil count or the mean of blood eosinophil counts was used.In a primary care population, the most recent blood eosinophil count could be used to guide initiation of ICS in COPD patients. We suggest that ICS should be considered in those with higher eosinophils and avoided in those with lower eosinophils (<150 cells·µL−1).

Highlights

Guidelines for pharmacological management of chronic obstructive pulmonary disease (COPD) recommend addition of inhaled corticosteroids (ICS) to bronchodilator therapy for worsening symptoms [1]
Using the Clinical Practice Research Datalink (CPRD), we investigated whether the most recent peripheral blood eosinophil count at the point of an inhaled treatment step-up or initiation decision could predict treatment outcomes, in a COPD ICS-naïve primary care population from 2005-2015
Our range of index dates were chosen to be after introduction of Quality and Outcomes Framework (QOF) targets in UK primary care which improved coding of COPD and spirometry [12], but before blood eosinophils were promoted as a potential biomarker, which might have influenced prescribing choices

Summary

Introduction

Guidelines for pharmacological management of chronic obstructive pulmonary disease (COPD) recommend addition of inhaled corticosteroids (ICS) to bronchodilator therapy for worsening symptoms (frequent exacerbations or persistent breathlessness) [1]. There is some benefit in reducing exacerbations, long-term effects of ICS on lung function decline and mortality are unclear. ICS use is associated with adverse effects including pneumonia and osteoporotic fractures, as well as being cumulatively expensive [2, 3]. ICS compounds are widely used in clinical practice [4]. In UK primary care, almost 2 in 5 patients prescribed an ICS did not meet criteria for this treatment [3]. There is an urgent need to improve clarity around when ICS should be prescribed

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