Effects of azithromycin in severe eosinophilic asthma with concomitant monoclonal antibody treatment

<bold>Introduction:</bold> Azithromycin reduces exacerbations in severe asthma with both low and high type-2 inflammation and is recommended as add-on therapy. However, it is unknown if it provides further benefits in severe asthma treated with monoclonal antibodies. <bold>Methods:</bold> We reviewed our cohort of 823 patients on biologics for asthma. 50 commenced azithromycin therapy after the start of biologics, including 37 with paired data points after at least one year of follow-up. We compared the median annual rate of oral corticosteroid (OCS)-treated and antibiotic-treated exacerbations in the period from the start of biologics to the start of azithromycin and the period between the start of azithromycin and the latest review. <bold>Results:</bold> Patients had a median of 1.8 (IQR 0.1-3.3) OCS-treated events per year and 2.0 (IQR 1.7-3.0) antibiotic-treated events per year prior to azithromycin, compared to 1.0 (IQR 0.2-2.0) and 1.3 (IQR 0.4-1.8) respectively after treatment, matched sample mean differences (95% CI) 1.0 (0.3–1.8), p<0.02, and 1.5 (1.0-2.1), p<0.001. Both elevated blood eosinophils (≥0.5x109/L) and low FeNO (<40 ppb), prior to biologics, showed a non-significant trend towards greater response. There was also a significant reduction in ACQ-5 after treatment of -0.95 ± 1.17 (mean ± SD), p<0.05. Adverse events were rare and self-limited. <bold>Conclusions:</bold> Azithromycin reduced the risk of clinically significant exacerbations and improved symptom scores when added to biologics in severe asthma. This effect may be shaped by baseline inflammatory biomarkers. Azithromycin could have clinical utility for persistent exacerbations prior to considering a change in monoclonal antibody agent.