TY - JOUR
T1 - Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease
T2 - a post-hoc analysis of three randomised trials
AU - Bafadhel, Mona
AU - Peterson, Stefan
AU - De Blas, Miguel A.
AU - Calverley, Peter M.
AU - Rennard, Stephen I.
AU - Richter, Kai
AU - Fagerås, Malin
N1 - Funding Information:
The original clinical studies, in addition to the current analyses, were funded by AstraZeneca. MB was funded by a National Institute of Health Research (NIHR) Post-doctoral Fellowship (PDF-2013-06-052) and presents independent research funded by the NIHR. MB has received honoraria and travel expenses for attendance at educational meetings from AstraZeneca, Chiesi, GlaxoSmithKline, Boehringer Ingelheim, Novartis, and Pfizer. SP is a statistical advisor at StatMind, which received funding from AstraZeneca to complete the statistical analyses. PMC has been a speaker at meetings supported by AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim, and is a Principal Investigator of studies supported by these companies. MADB, SIR, KR, and MF are employees of AstraZeneca. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/2
Y1 - 2018/2
N2 - Background: The peripheral blood eosinophil count might help identify those patients with chronic obstructive pulmonary disease (COPD) who will experience fewer exacerbations when taking inhaled corticosteroids (ICS). Previous post-hoc analyses have proposed eosinophil cutoffs that are both arbitrary and limited in evaluating complex interactions of treatment response. We modelled eosinophil count as a continuous variable to determine the characteristics that determine both exacerbation risk and clinical response to ICS in patients with COPD. Methods: We analysed data from three AstraZeneca randomised controlled trials of budesonide–formoterol in patients with COPD with a history of exacerbations and available blood eosinophil counts. Patients with any history of asthma were excluded. Negative binomial regression analysis was done using splines for modelling of continuous variables to study the primary outcome of annual exacerbation rate adjusted for exposure time and study design. The trials are registered with ClinicalTrials.gov, NCT00206167, NCT00206154, and NCT00419744. Findings: 4528 patients were studied. A non-linear increase in exacerbations occurred with increasing eosinophil count in patients who received formoterol alone. At eosinophil counts of 0·10 × 109 cells per L or more, a significant treatment effect was recorded for exacerbation reduction with budesonide–formoterol compared with formoterol alone (rate ratio 0·75, 95% CI 0·57–0·99; pinteraction=0·015). Interactions were observed between eosinophil count and the treatment effects of budesonide–formoterol over formoterol on St George's Respiratory Questionnaire (pinteraction=0·0043) and pre-bronchodilator FEV1 (linear effect p<0·0001, pinteraction=0·067). Only eosinophil count and smoking history were independent predictors of response to budesonide–formoterol in reducing exacerbations (eosinophil count, pinteraction=0·013; smoking history, pinteraction=0·015). Interpretation: In patients with COPD treated with formoterol, blood eosinophil count predicts exacerbation risk and the clinical response to ICS. Funding: AstraZeneca.
AB - Background: The peripheral blood eosinophil count might help identify those patients with chronic obstructive pulmonary disease (COPD) who will experience fewer exacerbations when taking inhaled corticosteroids (ICS). Previous post-hoc analyses have proposed eosinophil cutoffs that are both arbitrary and limited in evaluating complex interactions of treatment response. We modelled eosinophil count as a continuous variable to determine the characteristics that determine both exacerbation risk and clinical response to ICS in patients with COPD. Methods: We analysed data from three AstraZeneca randomised controlled trials of budesonide–formoterol in patients with COPD with a history of exacerbations and available blood eosinophil counts. Patients with any history of asthma were excluded. Negative binomial regression analysis was done using splines for modelling of continuous variables to study the primary outcome of annual exacerbation rate adjusted for exposure time and study design. The trials are registered with ClinicalTrials.gov, NCT00206167, NCT00206154, and NCT00419744. Findings: 4528 patients were studied. A non-linear increase in exacerbations occurred with increasing eosinophil count in patients who received formoterol alone. At eosinophil counts of 0·10 × 109 cells per L or more, a significant treatment effect was recorded for exacerbation reduction with budesonide–formoterol compared with formoterol alone (rate ratio 0·75, 95% CI 0·57–0·99; pinteraction=0·015). Interactions were observed between eosinophil count and the treatment effects of budesonide–formoterol over formoterol on St George's Respiratory Questionnaire (pinteraction=0·0043) and pre-bronchodilator FEV1 (linear effect p<0·0001, pinteraction=0·067). Only eosinophil count and smoking history were independent predictors of response to budesonide–formoterol in reducing exacerbations (eosinophil count, pinteraction=0·013; smoking history, pinteraction=0·015). Interpretation: In patients with COPD treated with formoterol, blood eosinophil count predicts exacerbation risk and the clinical response to ICS. Funding: AstraZeneca.
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U2 - 10.1016/S2213-2600(18)30006-7
DO - 10.1016/S2213-2600(18)30006-7
M3 - Article
C2 - 29331313
AN - SCOPUS:85040460999
VL - 6
SP - 117
EP - 126
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
SN - 2213-2600
IS - 2
ER -