Impact of azithromycin on serum inflammatory markers in children with cystic fibrosis and new Pseudomonas

Abstract

Chronic azithromycin improves outcomes in cystic fibrosis (CF), but its mechanism of action is unclear. The OPTIMIZE trial demonstrated improvement in time to first pulmonary exacerbation in children with new Pseudomonas treated with azithromycin. Azithromycin effect on systemic markers of inflammation over 18 months was assessed by change from baseline for high-sensitivity C-reactive protein, myeloperoxidase, calprotectin and absolute neutrophil count in the OPTIMIZE population. Subjects treated with chronic azithromycin or placebo had samples collected at baseline, 39 and 78 weeks of treatment. In 129 subjects, a significant decrease in high-sensitivity C-reactive protein was present at 39 weeks in the azithromycin group compared to placebo, but no significant difference between the groups at 78 weeks. No differences in change from baseline in myeloperoxidase, calprotectin or absolute neutrophil count were present at either time point. This supports the concept of a transient immunomodulatory effect for chronic azithromycin therapy in children with CF.

Keywords: Azithromycin; Cystic fibrosis; Inflammatory markers; Pseudomonas.

Figure 1.

Enrollment diagram of trial and analysis populations. The randomized trial was stopped early by the Data Safety Monitoring Board for efficacy of the primary endpoint - time to pulmonary exacerbation - and allowed to continue in an open label fashion thereafter. Our analysis cohort is comprised of 68 participants randomized to azithromycin and 61 to placebo for whom inflammatory marker data was available at baseline and at least one follow-up visit. For 24 of the azithromycin participants and 14 of the placebo participants, their follow up visit occurred after the study was unblinded by the DSMB, however their treatment (azithromycin or no azithromycin) remained the same in an open-label fashion. Placebo subjects included in the analysis cohort received no AZ after the study was unblinded and for the remainder of follow-up. AZ subjects included in the analysis cohort switched to prescription-based AZ after study unblinding and for the remainder of follow-up. Sensitivity analyses were additionally run using the cohort with follow-up data available only during the randomized study (n=47 placebo, n=47 azithromycin).