Clinical question: Does azithromycin decrease the frequency of asthma exacerbations in adults with persistent asthma symptoms despite use of inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA)?
Background: Asthma is a chronic inflammatory airway disease that is highly prevalent worldwide within a subset of people with asthma who have symptoms that are poorly controlled despite ICS and LABA maintenance therapy. Currently, add-on therapy options include monoclonal antibodies, which are cost prohibitive. The need for additional therapeutic options exists. At the same time, macrolide antibiotics are known to have anti-inflammatory, antiviral, and antibacterial effects and have proven to have beneficial effects on asthma symptoms.
Setting: Multiple sites throughout Australia.
Synopsis: The AMAZES trial enrolled 420 adult patients with symptomatic asthma despite current use of ICS and LABA. Patients were randomly assigned to receive azithromycin 500 mg or placebo three times a week for 48 weeks. Patients who had hearing impairment, prolonged QTc interval, or emphysema were excluded.
Azithromycin reduced the frequency of asthma exacerbations, compared with placebo (1.07 vs. 1.86 exacerbations/patient-year; incidence rate ratio 0.59; 95% confidence interval, 0.47-0.74; P less than .0001). It also significantly improved asthma-related quality of life according to the Asthma Quality of Life Questionnaire (adjusted mean difference, 0.36; 95% CI, 0.21-0.52; P = .001). Diarrhea occurred more commonly in the azithromycin group but did not result in a higher withdrawal rate.
A significant limitation of this study was generalizability, as the median patient age was 60 years and race was not reported. More research is needed to determine the effect of long-term azithromycin use on microbial resistance.
Bottom line: Adding azithromycin to maintenance ICS and LABA therapy in patients with symptomatic asthma decreased the frequency of asthma exacerbations and improved quality of life.
Citation: Gibson PG et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): A randomised, double-blind, placebo-controlled trial. Lancet. 2017 Aug 12;390(10095):659-68.
Dr. Farber is a medical instructor, Duke University Health System.