Azithromycin Add-On Improves Uncontrolled Asthma Outcomes

AUGUST 07, 2017
Kenneth Bender
Patients with asthma symptoms uncontrolled by inhaled corticosteroids and long-acting bronchodilators had fewer exacerbations of asthma and experienced improved quality of life with the addition of azithromycin, per a recently published long-term study.

The study was lauded as "landmark" in an accompanying editorial, for having a large sample of patients and long duration of treatment "to unequivocally show that add-on therapy with azithromycin in adult patients with uncontrolled asthma reduced exacerbation rates and improved quality of life."

Peter Gibson, MBBS, Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, Newcastle, NSW, Australia, and colleagues conducted the randomized, placebo-controlled study in 420 patients with uncontrolled asthma symptoms. Azithromyin 500mg 3 times weekly was added for 48 weeks to the corticosteroid and long-acting bronchodilator regimen of 213 patients, with 207 receiving add-on placebo.

Participants were required to be clinically stable for at least 4 weeks prior to the study and to be non-smokers, confirmed by exhaled carbon monoxide of less than 10 parts per million.  Ex-smokers were admitted into the study if their diffusing capacity for carbon monoxide was greater than 70% of predicted value. Those with hearing impairment or abnormally prolonged QTc interval were excluded. Asthmatic conditions were phenotyped as eosinophilic or non-eosinophic, and antibacterial effects were assessed with baseline and end-of-treatment sputum cultures. 

The antibiotic activity of azithromycin may not be a mechanism of action in asthma, but the possibility that it would present either a therapeutic or adverse condition was evaluated, Gibson told MD Magazine.

"We studied this issue fairly carefully.  We looked at any episode of any possible infection, and found no increase in clinical infective episodes on treatment, in fact there were significantly fewer respiratory infections on AZM (azithromycin)," Gibson said. "We assessed AZM resistant pathogens in sputum and saw a slight but statistically significant increase on treatment, however, it did not translate into more respiratory infections, in fact they had fewer infections."

The primary efficacy endpoint of the study was the total number of asthma exacerbations, severe and moderate, over the 48-week treatment, and asthma-related quality of life.  Severe exacerbations were defined as worsening symptoms that led to initiating or increasing systemic corticosteroid treatment, or hospitalization. Moderate exacerbations corresponded to a temporary increase in inhaled corticosteroid and/or antibiotics, increased beta2-agonist use, or an emergency department visit not requiring systemic corticosteroids. Quality of life was gauged with the Asthma-specific Quality of Life Questionnaire (AQLQ), measuring symptoms, emotions and environment domains.

Gibson and colleagues reported that patients treated with azithromycin had significantly fewer exacerbations than the placebo group, with 1.07 exacerbations per person-year (95% Confidence Interval 0.85-1.29) compared to 1.86 per person year (1.54-2.18). Azithromycin was associated with a reduced hazard ratio of 0.65 (95%CI 0.5-0.85), and the beneficial effect remained significant after adjustment for differences in such factors as inhaled corticosteroid dose, frequency of exacerbations, and presence of chronic cough. Azithromycin also significantly improved asthma-related quality of life (adjusted mean difference, 0.36 (95% CI 0.21-0.52).

The researchers characterized the efficacy of azithromycin as similar to that of monoclonal antibody treatment, with substantially less cost and greater accessibility. 

"Azithromycin could be considered before the introduction of monoclonal antibody therapy in patients with poorly controlled asthma...," they suggested.
The assessment of azithromycin as add-on treatment for persistent, uncontrolled asthma was published on-line July 4 in The Lancet.

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