TY - JOUR T1 - Does maintenance azithromycin reduce asthma exacerbations? An individual participant data meta-analysis JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01381-2019 SP - 1901381 AU - Sarah A. Hiles AU - Vanessa M. McDonald AU - Michelle Guilhermino AU - Guy G. Brusselle AU - Peter G. Gibson Y1 - 2019/01/01 UR - http://erj.ersjournals.com/content/early/2019/09/02/13993003.01381-2019.abstract N2 - 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Hiles’ salary was supported by a grant from GlaxoSmithKline paid to employer (University of Newcastle) during the conduct of the study; travel for collaboration was supported by a Hunter Medical Research Institute Jennie Thomas Medical Research Travel Grant; salary was supported by a grant from AstraZeneca paid to employer (University of Newcastle) outside the submitted work.Conflict of interest: Dr. McDonald reports grants from GSK, during the conduct of the study; grants and personal fees from GSK, grants and personal fees from Astra Zeneca, personal fees from Menarini, outside the submitted work.Conflict of interest: Dr. Guilhermino has nothing to disclose.Conflict of interest: Dr. Brusselle reports personal fees from Astra Zeneca, personal fees from Boehringer-Ingelheim, personal fees from Chiesi, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Sanofi, personal fees from Teva, outside the submitted work.Conflict of interest: Dr. Gibson reports grants and personal fees from AstraZeneca, GlaxoSmithKline, Novartis, outside the submitted work. ER -