Azithromycin Reduces Residual Exacerbations in Biologic-Treated Severe Asthma: A Single-Center Audit
In a retrospective audit from the Oxford Special Airways Clinic, adjunctive azithromycin therapy in patients with severe asthma already receiving biologics led to significant reductions in oral corticosteroid (OCS) and antibiotic-treated exacerbations. While symptom scores improved, lung function remained unchanged.
Despite the substantial benefits of biologics in type 2 asthma, a subset of patients continue to experience exacerbations, often driven by non-type 2 inflammatory pathways such as bacterial or viral infections.
Current guidelines recommend azithromycin for reducing exacerbations in severe asthma, yet its specific benefit for patients treated with biologics remain unclear. This study aimed to evaluate whether adding azithromycin could further reduce exacerbation rates in this clinical population.
Researchers conducted an audit of 818 patients treated with biologics at the Oxford Special Airways Clinic between 2008 and 2023. Of these, 50 patients initiated long-term azithromycin (≥ 3 months) after biologic therapy. A comparator group of 150 patients was randomly selected from the remaining cohort for baseline comparison. Exacerbations were measured using surrogate markers: OCS and antibiotic prescriptions. Outcomes included pre- and post-treatment event rates, Asthma Control Questionnaire-5 (ACQ-5) scores, and forced expiratory volume in one second (FEV1).
At baseline, patients treated with azithromycin were older (mean 61.7 vs 55.5 years) and had more frequent OCS-treated exacerbations (median 6 vs 4 per year). Chronic bronchitis or recurrent purulent exacerbations were present in 94% of patients treated with azithromycin compared with 21% of the comparator group.
After initiating azithromycin, paired data for 37 patients demonstrated a mean reduction in OCS-treated events of 1.0/year (95% CI, 0.3-1.8; P = 0.02) and in antibiotic-treated events of 1.5/year (95% CI, 1.0–2.1; P < 0.001). ACQ-5 scores significantly improved from 2.91 to 1.41 (mean difference −0.95; P = 0.04), but no significant change was observed in FEV1.
The response to azithromycin was not significantly associated with baseline demographics or clinical characteristics. A trend toward greater benefit was seen in patients with low fractional exhaled nitric oxide levels and positive sputum cultures, although these findings did not reach statistical significance. Safety data indicated common gastrointestinal side effects, liver and hearing issues were rare and self-limited, and no QT prolongation events were documented.
The study’s limitations include its retrospective design, small sample size, single-center setting, and the non-randomized nature of azithromycin treatment. Additionally, lack of systematic microbiologic data collection limited the ability to assess potential predictors of treatment response.
“Azithromycin should be considered in patients with severe asthma treated with biologics with residual exacerbations and symptoms of chronic bronchitis and/or purulent exacerbations,” the authors concluded.
Reference
Lavoie G, Howell I, Melhorn J, et al. Effects of azithromycin in severe eosinophilic asthma with concomitant monoclonal antibody treatment. Thorax. 2025;80(2):113-116. Published 2025 Jan 17. doi:10.1136/thorax-2024-221977