Effectiveness and safety of macrolides in cystic fibrosis patients: a meta-analysis and systematic review

Objectives: To evaluate the efficacy and safety of macrolides in cystic fibrosis (CF). Methods: Randomized controlled trials (RCTs) of macrolides for the treatment of CF published in PubMed, the Cochrane Library and Embase were searched. Application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality were independently performed in duplicate. The primary efficacy outcome was the impact on the deterioration of lung function (changes in FEV 1 and FVC). Safety outcomes included adverse events and mortality. Results: Eight RCTs (seven with azithromycin and one with clarithromycin) were found in the systematic review and six RCTs with azithromycin (654 patients) were included in the meta-analysis. Azithromycin treatment showed a significant increase in FEV 1 % (3.22%, 95% CI= 1 . 38 - 5 .0 6 , P= 0 . 0006 , I 2 =0% ) and FVC% (3.23%, 95% CI= 1 . 62 - 4 . 85 , P< 0.0001, I 2 =0%) compared with placebo. In individuals with baseline Pseudomonas aeruginosa colonization, both FEV 1 % (4.80%, 95% CI = 1.66-7.94, P=0.003, I 2 =42%) and FVC% (4.74%, 95% CI= 1 . 92 - 7 . 57 , P=0.00 1 , I 2 =0%) increased significantly. The incidence rates of the main side effects (cough, headache, abdominal pain, vomiting, nausea and diarrhoea) were not significantly different between the azithromycin-treated group and the placebo group. The RCT of clarithromycin, involving 18 patients, showed its effects on clinical improvement; however, the small sample size made comparisons with azithromycin difficult. Conclusions: Long-term use of azithromycin can improve lung function, especially for P. aeruginosa-colonized CF patients. There was no evidence of increased adverse events with azithromycin. More data are needed to verify the best azithromycin regimen and to evaluate other macrolides in CF patients.