Originally published: September 2017

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;390(10095):659-668

Long-term prophylactic macrolide antibiotics, such as azithromycin, are a useful treatment option in several respiratory conditions. Macrolide antibiotics, in addition to their antibacterial properties, exert anti-inflammatory effects via various mechanisms that are not fully understood. They have been shown to reduce exacerbations in cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease. However, the role of macrolide therapy in patients with asthma is less clear as a number of studies have been conducted with conflicting results.

Professor Peter Gibson and colleagues undertook the AMAZES trial, which was reported in the Lancet, August 2017. This was a randomised double-blind placebo-controlled trial of azithromycin 500 mg or placebo three times a week in 420 participants with uncontrolled, persistent asthma. The primary end-points were asthma exacerbations and asthma-related quality of life.

The authors report that azithromycin reduced the total number of asthma exacerbations (1.07 vs. 1.86 per patient per year), as well as the number of exacerbations requiring oral steroid treatment (0.61 vs. 1.07 per patient per year). Asthma related quality of life was also significantly improved by azithromycin. Secondary outcomes, including asthma symptoms and the need for rescue antibiotics, were also improved by azithromycin treatment. Azithromycin was generally well tolerated, though diarrhoea was more common in the azithromycin arm than the placebo arm (34% vs. 19%).

Finally, azithromycin reduced exacerbations in asthma where airway inflammation resulting from infection and neutrophils was predominant, but also, surprisingly, in subjects with eosinophil predominant airways inflammation.

Overall, this large, well-designed trial has shown that azithromycin can be a useful add-on therapy for uncontrolled, persistent asthma. Questions remain as to the right time to use this treatment and the right patient cohort to obtain the maximum effect. The long-term effects on airway microbiology and antibiotic resistance also need to be considered.

Dr Rahul Shrimanker is a clinical research fellow, University of Oxford.

*Azithromycin is not indicated for the treatment of asthma exacerbations in uncontrolled asthma. Follow link for azithromycin SPC: www.medicines.org.uk/emc/medicine/1477/

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