Azithromycin effective as adjunct therapy in uncontrolled asthma
The macrolide antibiotic azithromycin may be an effective adjunctive therapy for individuals whose asthma symptoms persist despite treatment with corticosteroids and bronchodilators, a recent study found.
“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,” said the researchers.
Trial participants were 420 adults (median age, 60 years, median asthma duration, 32 years) with uncontrolled symptomatic asthma (mean asthma control score [ACQ6], 1.55, mean forced expiratory volume in 1 second [FEV1], 73 percent) currently on maintenance therapy of inhaled corticosteroids and long-acting bronchodilators. They were randomized to receive oral azithromycin (500 mg, n=213, 63 percent female) or placebo (n=207, 58 percent female) three times a week for 48 weeks.
Patients on azithromycin demonstrated a reduced rate of asthma exacerbations compared with those on placebo (1.07 vs 1.86 per person-year; incidence rate ratio [IRR], 0.59; p<0.0001), a reduction evident in eosinophilic (0.96 vs 1.98 per person-year; IRR 0.52; p=0.030) and noneosinophilic asthma (1.15 vs 1.74 per person-year; IRR, 0.66; p=0.019). [Lancet 2017;doi:10.1016/S0140-6736(17)31281-3]
Compared with patients on placebo, a smaller proportion of patients on azithromycin experienced at least one asthma exacerbation (44 percent vs 61 percent; p<0.0001). Severe asthma exacerbation incidence was also lower among patients on azithromycin compared with placebo (0.61 vs 1.07 per person-year; IRR, 0.59; p=0.002), as was time to asthma exacerbation (hazard ratio, 0.65; p=0.001).
Patients on azithromycin also experienced improved asthma-related quality of life compared with patients on placebo (adjusted mean difference, 0.36; p=0.001).
Incidence of serious adverse events (AEs) was comparable between patients on azithromycin and placebo (8 percent vs 13 percent; p=0.27), though a higher incidence of diarrhoea was noted among patients on azithromycin (34 percent vs 19 percent; p=0.001).
Infection-related AEs were lower in the azithromycin vs placebo group (20 percent vs 36 percent; p<0.001), driven mostly by the lower incidence of respiratory tract infections (17 percent vs 31 percent; p=0.001).
“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,” said the researchers.
As a majority of the trial population was of older age, the researchers cautioned against applying the findings to children or young adults with asthma. The study was also not adequately powered to evaluate the impact of azithromycin on microbial resistance.
“[T]he effects of long-term therapy with macrolides on community microbial resistance remain a public health concern,” said Professor Guy Brusselle from Ghent University Hospital, Belgium, and Professor Ian Pavord from the Nuffield Department of Medicine, University of Oxford, Oxford, UK, in a commentary. [Lancet 2017;doi:10.1016/S0140-6736(17)31547-7]
“[A]dd-on therapy with azithromycin in asthma needs to be restricted to those patients with the highest unmet medical need ... and to time periods with the greatest risk of exacerbations,” they said, and called for further research into nonantibiotic macrolides for severe, uncontrolled asthma.