Heterogeneity of Treatment Response to Azithromycin in Patients with Cystic Fibrosis

Rationale: We recently reported a randomized, placebo-controlled trial of azithromycin in patients with cystic fibrosis (CF) that demonstrated a 6.2% improvement in the 168-d relative change in FEV1 among azithromycin participants compared with placebo participants.

Objectives: In the current analyses, heterogeneity of treatment response and the association between FEV1 and the risk of pulmonary exacerbations were investigated.

Methods: The time to first pulmonary exacerbation, hospitalization rates, and antibiotic use were compared between participants categorized by their relative change in FEV1 % predicted (>or= 5 vs. < 5% improvement) at Day 168. Pulmonary function and exacerbation responses were compared in subgroups of participants characterized by long-term concomitant medications and baseline lung function.

Measurements: All available data from the 185 randomized participants in the azithromycin trial were included in these analyses.

Main Results: Compared with placebo participants, a reduced risk of pulmonary exacerbations was observed both among azithromycin participants with >or= 5% and those with < 5% relative improvement in FEV1. Similarly, decreased hospitalization rates and decreased use of oral quinolone and nonquinolone antibiotics were observed in azithromycin participants regardless of improvement in FEV1. Subgroup analyses demonstrated that overall, participants on long-term aerosolized tobramycin and/or rhDNase had worse baseline lung function, but still benefited from azithromycin, as evidenced by a lower risk of exacerbations.

Conclusions: Azithromycin participants experienced benefits in exacerbation parameters regardless of FEV1 response or subgroup. These data have implications for clinical practice and the design of clinical trials.