Does maintenance azithromycin reduce asthma exacerbations? An individual participant data meta-analysis

Background Preventing exacerbations is an important goal of asthma treatment. Long-term treatment with azithromycin may help achieve this. Our aim was to conduct a systematic review and individual participant data (IPD) meta-analysis to examine the efficacy of azithromycin in reducing exacerbations in asthma, and the sub-phenotypes of non-eosinophilic asthma, eosinophilic asthma and severe asthma. Method We completed a systematic search of EMBASE, Medline, Pubmed, Cochrane Library, ClinicalTrails.gov and reference lists of previous systematic reviews in February 2019. We included parallel-group double-blind randomised controlled trials in adults comparing at least 8 weeks of azithromycin treatment with placebo, where the outcome of exacerbations was assessed over at least 6 months. Data were extracted from published sources, Cochrane risk of bias tool was applied and IPD were sought from authors. Reviews were undertaken in duplicate. We conducted an IPD meta-analysis on the primary outcome of exacerbations and a random effects meta-analysis for secondary outcomes. PROSPERO registration: CRD42018075259. Results Three studies were identified (N=597). In the IPD meta-analysis, treatment with azithromycin was associated with a reduced rate of exacerbations (oral corticosteroid course due to worsening asthma, antibiotic use for lower respiratory tract infection, hospitalisation, and/or emergency room visits) in asthma and in the non-eosinophilic, eosinophilic and severe asthma subgroups. Examining each exacerbation type separately, patients with eosinophilic asthma reported fewer oral corticosteroids courses and patients with non-eosinophilic and severe asthma reported fewer antibiotic courses. Azithromycin was well tolerated. Discussion Maintenance use of azithromycin reduces exacerbations in patients with eosinophilic, non-eosinophilic and severe asthma.