An 18-month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis

Abstract

Chronic airway infection with Pseudomonas aeruginosa (PA) causes morbidity and mortality in patients with cystic fibrosis (CF). Additional anti-PA therapies are needed to improve health status and health-related quality of life. AIR-CF3 was an international 18-month, open-label study to evaluate the safety and efficacy of repeated courses of aztreonam for inhalation solution (AZLI, now marketed as Cayston®) in patients aged ≥ 6 years with CF and PA infection who previously participated in one of two Phase 3 studies: AIR-CF1 or AIR-CF2. Patients received up to nine courses (28 days on/28 days off) of 75 mg AZLI two (BID) or three times daily (TID) based on randomization in the previous trials. 274 patients, mean age 28.5 years (range: 8-74 years), participated. Mean treatment adherence was high (92.0% BID group, 88.0% TID group). Hospitalization rates were low and adverse events were consistent with CF. With each course of AZLI, FEV(1) and scores on the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom scale improved and bacterial density in sputum was reduced. Benefits waned in the 28 days off therapy, but weight gain was sustained over the 18 months. There were no sustained decreases in PA susceptibility. A dose response was observed; AZLI TID-treated patients demonstrated greater improvements in lung function and respiratory symptoms over 18 months. Repeated intermittent 28-day courses of AZLI treatment were well tolerated. Clinical benefits in pulmonary function, health-related quality of life, and weight were observed with each course of therapy. AZLI is a safe and effective new therapy in patients with CF and PA airway infection.

Conflict of interest statement

Conflict of Interest Statement: Dr. Oermann received clinical research support as a site investigator conducting clinical trials for Gilead Sciences and Inspire Pharmaceuticals. Dr. Retsch-Bogart received clinical research support as a site investigator conducting clinical trial for Gilead Sciences, Inspire Pharmaceuticals, Genentech, Pathogenesis Corp., Boehringer-Ingelheim, and Cystic Fibrosis Foundation Therapeutics, Inc. Dr. Quittner was a consultant, served on an advisory board for Gilead Sciences, and has an investigator-initiated grant in another population. Dr. Gibson received clinical research support as a site investigator conducting clinical trials for Gilead Sciences, Inspire Pharmaceuticals, and Cystic Fibrosis Foundation Therapeutics. Dr. McCoy received clinical research support as a site investigator conducting clinical trials for Gilead Sciences, Inspire Pharmaceuticals, and Genentech. Dr. Montgomery is employed by Gilead Sciences. He is patent author on aztreonam for inhalation solution and Gilead Sciences is patent holder. He holds equity interest in Gilead Sciences. Dr. Cooper received clinical research support as a site investigator for clinical trials sponsored by Gilead Sciences.

Figures

Fig. 1

Study design and patient disposition.

Fig. 2

Time to intravenous antipseudomonal antibiotics (days).

Fig. 3

Mean change (±SE) in weight (A) and mean change in CFQ-R weight domain score (B) from baseline to study end.

Fig. 4

MIC50 and MIC90 of aztreonam for Pseudomonas aeruginosa isolates with the highest MIC from each patient (µg/ml): baseline to study end.