Efficacy of azithromycin in severe asthma from the AMAZES randomised trial

Background: Low-dose azithromycin is an effective therapy for persistent asthma; however, its benefit in severe asthma is not defined. Methods: Participants with severe asthma were identified from the AMAZES randomised, placebo-controlled trial of long-term (48 weeks) low-dose azithromycin. Participants who met one of the following severe asthma definitions were included: 1) Global Initiative for Asthma step 4 treatment with poor asthma control (asthma control questionnaire score ≥0.75); 2) International Severe Asthma Registry definition; 3) American Thoracic Society and European Respiratory Society severe asthma definitions. The rate of total exacerbations was calculated for each subgroup and efficacy of azithromycin compared with placebo. Asthma-related quality of life was assessed before and after treatment along with adverse effects. Results: Azithromycin significantly reduced asthma exacerbations in each group. In patients meeting the American Thoracic Society and European Respiratory Society task force definition of severe asthma (n=211), the rate of exacerbations with treatment was 1.2 per person-year, which was significantly less than for placebo (2.01 per person-year), giving an incidence rate ratio (95% CI) of 0.63 (0.41, 0.96). The proportion of participants experiencing at least one asthma exacerbation was reduced by azithromycin from 64% to 49% (p=0.021). A similar beneficial treatment effect was seen in participants poorly controlled with Global Initiative for Asthma step 4 treatment and those with International Severe Asthma Registry-defined severe asthma. Azithromycin also significantly improved the quality of life in severe asthma (p<0.05). Treatment was well tolerated, with gastrointestinal symptoms being the main adverse effect. Conclusion: Long-term, low-dose azithromycin reduced asthma exacerbations and improved the quality of life in patients with severe asthma, regardless of how this was defined. These data support the addition of azithromycin as a treatment option for patients with severe asthma.