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

Abstract

BackgroundIn 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.MethodsEnrolment 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.ResultsAzithromycin 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/μL, 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.ConclusionsThis 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.Trial registrationClinicalTrials.gov number. NCT02135354.

A Multicenter Study to Identify the Respiratory Pathogens Associated with Exacerbation of Chronic Obstructive Pulmonary Disease in Korea

“…During AE-COPD, the host immune system may not be able to easily eliminate microorganisms in the lower airways because the phagocytic functions of macrophages and neutrophils are impaired 11 . Therefore, an appropriate choice of antibiotic agent is required to reduce treatment failure or mortality 12,13 . As antibiotic agents should be chosen based on the local microbiologic spectrum, it is important to investigate the epidemiologic pattern of pathogenic bacterial and viral species in AE-COPD patients.…”

Local expression profiles of vitamin D-related genes in airways of COPD patients

“…Current therapies mainly focus on bronchodilation by using combined therapies of long-acting β 2 -adrenergic agonists and anticholinergics [1]. Inhaled corticosteroids or azithromycin are used to decrease exacerbation frequency however, effectiveness is more pronounced in specific subgroups [3,4]. As exacerbations are driving symptoms and compose a significant burden on our healthcare system, there is an obvious need for more powerful anti-inflammatory and immunomodulating agents [5].…”

Predicting and preventing hospital readmission for exacerbations of COPD

“…In another study, high C-reactive protein (CRP) levels in patients with peripheral blood eosinophils ⩽2% were associated with increased risk of hospital readmission [49]. In a subgroup of hospitalised COPD patients with elevated CRP, the rate of subsequent hospital readmission was reduced following treatment with low-dose azithromycin over 3 months [50]. Measuring the systemic inflammatory response by utilising CRP concentration may be a useful marker to predict the outcome of COPD exacerbations and allow the identification of patients at risk of recurrent exacerbations for specific treatment and follow-up.…”