Adults with persistent symptomatic asthma who took azithromycin as an add-on therapy experienced fewer exacerbations and had improved quality of life, compared with their peers who took a placebo, a multicenter, randomized trial demonstrated.
“Macrolide antibiotics have antibacterial, antiviral, and anti-inflammatory effects, and are reported to be beneficial in both eosinophilic and noneosinophilic subtypes,” a group of Australian researchers wrote online July 4 in The Lancet (doi: org/10.1016/S0140-6736[17]31281-3). “Systematic reviews of randomized, controlled trials report benefits of macrolides on asthma symptoms but [we] are unable to draw conclusions about the effects on other endpoints, including exacerbations, due to lack of data, heterogeneity of results, and inadequate study design and sample size.”
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The researchers observed a significant reduction in the incidence of total asthma exacerbations in the azithromycin-treated group: 1.07/patient-year, compared with 1.86/patient year in the placebo group, which translated into an incidence rate ratio of 0.59 (P less than .0001). Specifically, 127 patients in the placebo group (61%) experienced at least one asthma exacerbation compared with 94 patients in the azithromycin group (44%; P less than .0001). A significant improvement in asthma-related quality of life was also seen among patients in the azithromycin group (adjusted mean difference of 0.36; P = .001).
Though the mechanism of the antiviral effect of macrolides is not yet determined, Dr. Gibson and his associates noted that respiratory viral infection is associated with severe exacerbations in eosinophilic asthma and causes most respiratory infections. “There is a known interaction between eosinophilic airway inflammation, exacerbation rate, and impaired innate antiviral immunity,” they wrote. “Since we observed a benefit of azithromycin on both asthma exacerbations and respiratory infections, we speculate that azithromycin might be acting to prevent viral-induced episodes in asthma.”
“Given the major impact of asthma exacerbations on patients and the community and the ongoing risk posed by these events in patients who remain symptomatic on maintenance therapy, we consider that azithromycin is a valuable addition to existing regimens for treating asthma,” the researchers concluded. “The long-term effects of this therapy on community microbial resistance require further evaluation.”
The overall rates and types of serious adverse events seen in both groups were not significantly different from each other, with serious adverse events having occurred in 16 (8%) patients treated with azithromycin and 26 (13%) patients given the placebo.
The study was funded by the National Health and Medical Research Council of Australia and the John Hunter Hospital Charitable Trust. The authors reported having no financial conflicts directly related to the study.