Longterm Effect of Azithromycin in Bronchiolitis Obliterans Syndrome after Lung Transplantation; Post Hoc Analysis of a Randomized Trial

Abstract

Background: Azithromycin has been shown to stabilize and improve lung function (FEV1) in lung transplantation patients with bronchiolitis obliterans syndrome (BOS). We performed a post hoc analysis to assess the long term effect on FEV1, progression of BOS, and survival in patients initially randomized to placebo or azithromycin. Methods: Forty-eight patients were recruited between November 2006 and December 2010 for the randomized placebo controlled trial. After 3 months all patients received open label azithromycin and were followed up until 6 years after inclusion. FEV1, BOS free progression and overall survival were assessed. Follow-up data from 45 patients was available for analysis, 22 had initially received azithromycin and 23 placebo. Findings: FEV1 in the placebo group improved after open label azithromycin and was comparable to the treatment group by 6 months (FEV1 70% ± 4 vs 72% ±5). FEV1 subsequently decreased in both groups (67% ±4 and 57% ±7 vs 72% ± 5 and 59% NS) after 1 and 5 years. Progression free survival (log-rank test p = 0.40) and overall survival (log-rank test p = 0.28) was not significantly different between the groups. In the open label period survival of patients with early BOS (< median = 2.55 year) was not different than late onset of BOS (log-rank test p = 0.74). Interpretation: Long term treatment with azithromycin slows down the progression of BOS. BOS progression and long term survival were not affected by randomization to the placebo group. Thus performing randomized placebo controlled trials in lung transplantation patients with BOS with a blinded trial duration is feasible, effective and safe. Funding: None. Declaration of Interest: Dr Christiaan Tji-Joong Gan was the recipient of the European Respiratory Society Clinical Fellowship 2015 Ethical Approval: All patients provided written informed consent before randomization. The institutional review board approved the study.