November 2, 2010 (Baltimore, Maryland) — Inhaled aztreonam (Cayston) was associated with better lung function and fewer pulmonary exacerbations in cystic fibrosis than inhaled tobramycin, according to a 6-month industry-sponsored comparison study presented here at the North American Cystic Fibrosis 24th Annual Conference.
Both medications, prescribed for the treatment of Pseudomonas aeruginosa, had similar safety profiles during the study period, reported lead investigator Christopher M. Oermann, MD, associate professor of pediatrics at Baylor College of Medicine and director of the Cystic Fibrosis Care Center at Texas Children's Hospital in Houston.
With its approval by the US Food and Drug Administration (FDA) earlier this year, inhaled aztreonam "adds a powerful new option to the treatment of chronic [P aeruginosa] airway infection in [cystic fibrosis]," said Dr. Oermann in an interview with Medscape Medical News. "Rather than a single inhaled antibiotic, we now have 2."
The study involved 268 cystic fibrosis patients infected with P aeruginosa who were randomized to receive 28 days of either aztreonam (n = 136) or tobramycin (n = 132) followed by 28 days of no treatment intermittently for 6 months (3 treatment cycles).
Both treatments were nebulized. Aztreonam dosage was 75 mg 3 times daily, and tobramycin dosage was 300 mg twice daily.
To be included in the study, all patients had to be 6 years of age or older, and to have a chronic P aeruginosa infection, stable pulmonary disease, and a baseline forced expiratory volume in 1 second (FEV1) of 75% of predicted values or greater.
The mean age of the patients was 25.5 years, and 22% of them were younger than 18 years.
Lung function, measured as FEV1, was similar in both groups at baseline (about 52% of predicted), as were other respiratory symptoms, which were measured by the Cystic Fibrosis Questionnaire Revised.
When lung function was assessed over the 3 treatment cycles, patients treated with aztreonam had significant improvements, compared with those treated with tobramycin.
In fact, while FEV1 improved by a mean of 2% in the aztreonam group, it worsened by a mean of 0.7% in the tobramycin group, resulting in a 2.7% difference over the 3 cycles.
There was also a 31% reduction in both pulmonary exacerbations requiring hospitalization (40 vs 58 patients) and pulmonary exacerbations requiring additional anti–P aeruginosa antibiotics (84 vs 121 patients) in the aztreonam group, compared with the tobramycin group, over the 6 months.
Additionally, aztreonam-treated patients scored significantly better on symptom-related quality-of-life measures over the study period than tobramycin-treated patients.
The study was designed to demonstrate noninferiority in order to meet European regulatory requirements, and superiority to meet FDA requirements, explained Dr. Oermann. Consequently, the researchers looked at treatment outcomes at 28 days and at 6 months, and measured relative change and actual change in lung function. On all these measures, aztreonam was significantly more effective than tobramycin, he said.
Reached for comment on the study, Patrick A. Flume, MD, director of the Cystic Fibrosis Center and professor of medicine and pediatrics at the Medical University of South Carolina in Charleston, said: "I am pleased that we now have 2 approved drugs for aerosolization for patients with [cystic fibrosis]. Some patients cannot tolerate tobramycin, and now there is another option with acceptable safety data. I anticipate there will be patients who cannot tolerate aztreonam as well."
Dr. Flume urged caution in interpreting the nonefficacy of tobramycin in this study because there was no placebo group. Dr. Oermann speculated that the lack of robust response in the tobramycin-treated patients could indicate some degree of resistance.
Approximately 85% of patients in the study had received at least 3 courses of inhaled tobramycin in the year preceding the study; they were divided about equally between the 2 treatment groups. Multidrug resistant P aeruginosa was present in 30.4% of the aztreonam group and in 31.8% of the tobramycin group.
Dr. Flume, who was lead author of the Cystic Fibrosis Pulmonary Guidelines on Chronic Medications for Maintenance of Lung Health (Am J Respir Crit Care Med. 2007;176:957-969), said that "inhaled aztreonam was not included in the guidelines because there was no published evidence at the time of the review."
He added that "there is a plan for an updated review on chronic therapies in the very near future. It is highly likely that the committee will include aztreonam in its systematic review, and all published literature that meets the explicit criteria will be reviewed."
The study was supported by Gilead Sciences. Dr. Oermann reports that he serves on no pharmaceutical advisory boards or speakers bureaus. Dr. Flume reports that he receives grants and research support from Boehringer Ingelheim, Gilead, Mpex, Pharmaxis, and Vertex.
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Cite this: Study Shows Benefits of Aztreonam Over Tobramycin in Cystic Fibrosis - Medscape - Nov 02, 2010.
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