Use of Azithromycin in COPD

Tuesday, February 12, 2019

11:31 PM

Azithromycin for Prevention of Exacerbations of COPD

Albert et al. N Engl J Med 2011; 365:689-698 DOI: 10.1056/NEJMoa1104623
From <https://www.nejm.org/doi/full/10.1056/nejmoa1104623>

Background:
More COPD exacerbations cause
Increased $ of treatment
Increased risk of death
More rapid decline in function
Reduced QOL
Patients on ICS, LABA, LAMA: reduction in exacerbations but still 1.4 avg per year
Macrolide antibiotics are immunomodulatory, anti-inflammatory, antibacterial

Question:
Does azithromycin decrease frequency of exacerbations in pts with COPD who has an increased risk of
exacerbations?

Methods:
1577 subjects, 1142 randomly assigned, 570 to azithro 500mg group, 572 to placebo group
Inclusion criteria
>=40 years of age
had a clinical diagnosis of COPD (defined as having a smoking history of at least 10 pack-
years, a ratio of postbronchodilator FEV1/FVC of <70%, and a postbronchodilator FEV1 of
<80% of the predicted value)
were either using continuous supplemental oxygen or had received systemic glucocorticoids
within the previous year
had gone to an emergency room or had been hospitalized for an acute exacerbation of
COPD
had not had an acute exacerbation of COPD for at least 4 weeks before enrollment
Exclusion criteria
Asthma
a resting heart rate greater than 100 beats per minute
a prolonged corrected QT (QTc) interval (>450 msec)
the use of medications that prolong the QTc interval or are associated with torsades de
pointes (with the exception of amiodarone)
hearing impairment documented by audiometric testing
Followed for one year
Measured outcome of first acute exacerbation:
acute exacerbation of COPD defined as “a complex of respiratory symptoms (increased or new
onset) of more than one of the following: cough, sputum, wheezing, dyspnea, or chest tightness
with a duration of at least 3 days requiring treatment with antibiotics or systemic steroids.”
Results:
Azithro group Placebo

% follow up 89 90

Days until exacerbation 266 174

Exacerbations/pt-yr 1.48 1.83

Improvement in St George Respiratory Questionnaire scores More Less

%Clinically important difference in SGRQ scores 43 36

incidence of colonization with respiratory flora Decrease

incidence of colonization with macrolide-resistant organisms Increase

Hazard ratio for having acute exacerbation of COPD = 0.73
Hearing decrements more common in azithro group
Subgroup analyses: azithro has more effect in older (age>=65) and in non-smokers; less effect in COPD
hospitalization, steroid use in past year, ICS use at enrollment

Conclusions:
Adding azithromycin 250mg daily to usual treatment regimen of COPD exacerbation
1. Reduced frequency of exacerbations
2. Improved QOL
3. Hearing decrements in small population (improvements in hearing that occurred on repeat
testing, regardless of whether the study drug was discontinued)

Strengths:
40% female subjects

Weaknesses:
80% white subjects
Inclusion criteria stringent: Our results should be applied only to patients with COPD who either
require supplemental oxygen or have had acute exacerbations and who do not have resting
tachycardia or prolongation of the QTc interval, are not taking medications associated with QTc
prolongation, and do not have hearing abnormalities that place them below the 95th percentile of
patients of similar age.