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 (≥ 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 ≥ 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.