Long-term Treatment with Kalydeco Decreases Risk of Lung Infection, Study Reports

Treatment for three years with Kalydeco (ivacaftor) reduces the risk of lung infection by serious pathogens — including Pseudomonas aeruginosa and Staphylococcus aureus — in people with cystic fibrosis (CF), a U.K. study reports.

The study, “Ivacaftor Is Associated with Reduced Lung Infection by Key Cystic Fibrosis Pathogens: A Cohort Study Using National Registry Data,” was published in the journal Annals of the American Thoracic Society.

Marketed by Vertex Pharmaceuticals, Kalydeco is an approved therapy for CF patients carrying specific mutations in the CFTR gene — the defective gene that is the hallmark of cystic fibrosis. The therapy rescues the CFTR protein, a “gate” protein that controls the movement of charged salts, such as chloride, in and out of cells. It works by keeping the CFTR gate open longer.

Kalydeco was shown to improve lung function, exercise capacity, and sweat chloride concentration in CF patients, even in those with severe lung disease.

In in vitro (in the lab) studies, Kalydeco also was found to carry antibacterial properties. However, whether it could inhibit bacterial growth in the long run remained unknown.

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To decrease the risk of infection, especially by the classical CF pathogens Pseudomonas aeruginosa and Staphylococcus aureus, people with the disease often undergo long-term treatment with antibiotics. This, however, carries a significant burden for patients — and may increase the risk for antibiotic resistance.

“People with CF 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, a CF physician at Liverpool Heart & Chest Hospital and the study’s first author, said in a press release.

“At present, we simply don’t know whether it’s safe to stop some of those other treatments,” Frost added.

To investigate the impact of Kalydeco on CF patients’ risk of acquiring bacterial infections, the researchers used data from the UK Cystic Fibrosis Registry. Specifically, they compared the prevalence — over three years — of key CF bacteria in people (age six and older) treated with Kalydeco to that of patients who did not receive the therapy (the control group).

In total, the researchers analyzed data from 276 patients who had been treated with Kalydeco versus 5,296 people in the control group.

Results showed that prior to Kalydeco, the prevalence of P. aeruginosa was similar in both groups — 46.4% in the Kalydeco-treated group, and 47.9%  in the control group.

However, after the start of treatment with Kalydeco in 2013, the annual prevalence of P. aeruginosa declined for over three years, between 2014 and 2016 (40.6%, 37%, and 35.9%). Meanwhile, in the control group, its prevalence increased (53%, 53.3%, and 54.8%). The prevalence of other pathogens, including S. aureus, and Aspergillus spp, also declined. The only exception was Burkholderia cepacia complex.

Overall, the number of people with CF who were infected with P. aeruginosa declined by 32% after treatment with Kalydeco. A 15% drop was found in the number of people infected with S. aureus after Kalydeco therapy.

Kalydeco enhanced clearance of the bacteria in CF patients already infected (37.9%) compared with controls (22.8%). It also reduced the risk of infection by uninfected patients (24.6% vs 48.6%).

Overall, the findings indicate that long-term treatment with Kalydeco reduces the risk of infection by serious CF pathogens, such as P. aeruginosa. The results also suggest it may be safe to reduce long-term antibiotic treatment in certain patients.

“The fact we have seen reduced infections in this study suggests there may be some people who can safely discontinue medications targeted towards those infections,” Frost said.

“However, randomized, controlled trials will be needed to know if it is safe to reduce the overall treatment burden of CF by decreasing antibiotic use in patients taking ivacaftor or other drugs that target defects in the CF gene,” Frost added.

The results also suggest that treatment with Kalydeco and other CFTR modulators from an early age may help halt the risk of these infections.

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