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Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial

Journal Contribution - Journal Article

In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality. Background: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality.Objectives: (1) To investigate the intervention's effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions.Methods: Enrolment criteria included the diagnosis of COPD, a smoking history of >= 10 pack-years and >= 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time.Results: Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p = 0.005), or low blood eosinophil count (<300cells/mu L, RR = 0.33, 95%CI:0.17;0.64, p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses. Conclusions: This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy.
Journal: Respiratory Research
ISSN: 1465-993X
Issue: 1
Volume: 20
Publication year:2019
Keywords:Recurrent event, Readmission, Macrolide, CRP, Eosinophil count
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:1
CSS-citation score:1
Authors from:Higher Education, Hospital
Accessibility:Open