Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation. Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes. Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.

Methods: This post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies. Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study. Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study.

Results: Exacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150-300 cells/μL and 20.1% with > 300 cells/μL. The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count. When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150-300 cells/μL and 0.44 for > 300 cells/μL respectively). A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively. For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150-300 cells/μL) and 1.07 (> 300 cells/μL). Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49).

Conclusion: We found no clinically important relationship between baseline blood eosinophil count and exacerbation rate. Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations.

Trial registration: ClinicalTrials.gov Identifiers: NCT00168844 , NCT00168831 , NCT00387088 , NCT00782210 , NCT00782509 , NCT00793624 , NCT00796653 , NCT01431274 , NCT01431287 , NCT02296138 and NCT00975195 .

Keywords: Clinically irrelevant; Eosinophils; Exacerbations; ICS; Pooled; Randomized controlled trials; Rate ratio.

Conflict of interest statement

DS reports personal fees from Apellis, Cipla, Genentech, Peptinnovate and Skyepharma, and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Glenmark, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Theravance and Verona, outside the submitted work. JAW reports grants from GlaxoSmithKline, Johnson and Johnson, AstraZeneca, Boehringer Ingelheim and Novartis, and other from Novartis, Boehringer Ingelheim, AstraZeneca and GlaxoSmithKline, outside the submitted work. SS reports personal fees and other from Boehringer Ingelheim and Chiesi, and personal fees from GlaxoSmithKline, AstraZeneca, ERT Medical, Owlstone Medical, Mundipharma and Novartis, outside the submitted work. AdlH and WX are both employees of BI. HM reports personal fees from AstraZeneca, Boehringer Ingelheim, Novartis and ndd, during the conduct of the study. MM reports personal fees from Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, AstraZeneca, Teva, Kamada, Zambon, Grifols, Novartis, Gebro Pharma, CSL Behring, Cipla, MedImmune, Mereo BioPharma and Sandoz, and grants from GlaxoSmithKline and Grifols, outside the submitted work. JDC reports grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, Zambon, Insmed, Grifols, Novartis and AstraZeneca, grants from Gilead, and personal fees from Napp, outside the submitted work. PMAC reports grants and personal fees from GlaxoSmithKline, personal fees from AstraZeneca, Boehringer Ingelheim, Recipharm and Zambon, and personal fees and other from Boehringer Ingelheim, outside the submitted work.

Figures

Fig. 1

Baseline blood eosinophil levels in the total population. Baseline blood eosinophil count from 22,125 patients with accompanying exacerbation data

Fig. 2

a Eosinophil count at baseline by exacerbation history. b Eosinophil count at baseline by ICS use. ICS, inhaled corticosteroids