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Ivacaftor may reduce respiratory infections in cystic fibrosis

Among patients with cystic fibrosis, the use of ivacaftor was associated with a 32% reduction in the rate of Pseudomonas aeruginosa infection and a 15% reduction in the rate of Staphylococcus aureus infection over time, according to data published in the Annals of the American Thoracic Society.

“People with [cystic fibrosis] notice improvement in lung function and quality of life soon after they start taking ivacaftor, but they still have to live with a considerable treatment burden from all the other medications they take,” Freddy Frost, BMBS, BMedSci, from the Liverpool Adult Cystic Fibrosis Centre, Liverpool Heart and Chest Hospital NHS Foundation Trust and the Institute of Infection and Global Health, University of Liverpool, United Kingdom, said in a press release. “At present, we simply don’t know whether it’s safe to stop some of those other treatments. The fact we have seen reduced infections in this study suggests there may be some people who can safely discontinue medications targeted toward those infections.”

For the retrospective cohort study, Frost and colleagues analyzed data from the UK Cystic Fibrosis Registry from 2011 to 2016. The database contains information on demographics, clinical care, medication use and health outcomes for patients with cystic fibrosis. In 2016, the number of respiratory cultures and the number positive for P. aeruginosa were also available. The primary outcome was the annual prevalence ratios for each cystic fibrosis pathogen and secondary outcomes included time to infection in those who were previously not infected and time to P. aeruginosa clearance in those previously infected.

The treatment group (n = 276) included patients with at least one documented G551D mutation, those treated with ivacaftor (Kaleydeco, Vertex) from 2013 to 2016 and those who had complete microbiology data. The remainder of patients with cystic fibrosis formed the comparator group (n = 5,296).

The researchers only included patients older than 6 years in the overall cohort.

Lower rates of infection

Results showed that, among patients treated with ivacaftor, the annual prevalence of P. aeruginosa decreased from 48.9% in 2013 to 35.9% in 2016, with reductions seen each year. The annual prevalence of S. aureus also declined from 2013 to 2016, although the decreases were less pronounced (33.3% in 2013 to 30.1% in 2016). The prevalence for Aspergillus spp. also declined 12% to 4.7%, but the change in prevalence of Burkholderia cepacia was less than 1%.

In 2014, the use of ivacaftor vs. nonuse was associated with a reduced rate of positive culture for P. aeruginosa (adjusted prevalence ratio [aPR] = 0.78; 95% CI, 0.68-0.89) and Aspergillus spp. (aPR = 0.56; 95% CI, 0.4-0.77). However, the reduction in the rate of cultures positive for S. aureus was not significant (aPR = 0.92; 95% CI, 0.76-1.1).

By 2016, there was a 32% reduction in the prevalence ratio of P. aeruginosa (aPR = 0.68; 95% CI, 0.58-0.79). The change was less pronounced, however, for S. aureus after 3 years of treatment (aPR = 0.85; 95% CI, 0.7-1.01).

The reduction in aPR was attributable to higher clearance rates in patients treated with ivacaftor vs. those not treated with ivacaftor among patients who had documented P. aeruginosa growth in the 2 years before 2013 (37.9% vs. 22.8%; P < .001) and lower rates of P. aeruginosa in the ivacaftor group vs. the group not treated with ivacaftor among patients who did not have growth before 2013 (36.6% vs. 48.6%; P = .01).

Potential implications

Although the study is a retrospective study, it shows promise for ivacaftor to improve clinical outcomes for patients with cystic fibrosis, according to the researchers.

“If these drugs are taken before chronic infection starts, the risk of developing infection in the future may be reduced considerably,” Frost said in the release.

He also noted that the study adds to the evidence supporting the long-term benefits of ivacaftor.

“However, randomized controlled trials will be needed to know if it is safe to reduce the overall treatment burden of [cystic fibrosis] by decreasing antibiotic use in patients taking ivacaftor or other drugs that target defects in the [cystic fibrosis] gene,” Frost said. – by Melissa Foster

Disclosures: Healio Pulmonology could not confirm the authors’ relevant financial disclosures at the time of publication.