Rzeszów, Poland – One year of treatment with Kaftrio significantly reduced levels of key inflammatory immune cells, lowered the frequency of pulmonary exacerbations, and decreased detection of Pseudomonas aeruginosa in people with cystic fibrosis (CF), according to a real-world study. The anti-inflammatory effects were most pronounced in patients who had better lung function before starting therapy. Kaftrio is marketed as Trikafta in the U.S.
The findings, published in Respiratory Medicine in the study, “Changes in peripheral blood leukocyte profiles during elexacaftor/tezacaftor/ivacaftor therapy in cystic fibrosis according to baseline lung function,” add to growing evidence that Kaftrio provides benefits beyond improving CFTR protein function.
Kaftrio’s impact on inflammation
CF is caused by mutations in the CFTR gene, resulting in the production of thick, sticky mucus that accumulates in organs such as the lungs. This impairs the body’s ability to clear microbes, leading to chronic infections, persistent inflammation, and progressive lung damage.
One of the most problematic infections in CF is Pseudomonas aeruginosa, which is associated with faster lung function decline and an increased risk of death.
Kaftrio, developed by Vertex Pharmaceuticals, is a CFTR modulator that improves the production and function of defective CFTR protein in eligible patients. Clinical trials have shown that the therapy improves lung function, nutritional status, and quality of life while reducing pulmonary exacerbations. Emerging evidence also suggests it can dampen inflammation and reduce chronic bacterial infections.
Neutrophils and monocytes, two types of white blood cells involved in the immune response, are known to contribute to chronic inflammation and tissue damage in CF. Elevated levels of these cells are considered markers of systemic inflammation, but real-world evidence on how Kaftrio affects them has remained limited.
Study design
Researchers in Poland evaluated 28 people with CF, aged 12 years and older, who had received Kaftrio for at least one year at a single treatment center.
Blood samples were collected before treatment and after six and 12 months to measure white blood cell counts. Researchers also recorded pulmonary exacerbations requiring intravenous antibiotics and monitored respiratory samples for the presence of P. aeruginosa.
Participants were divided according to their baseline FEV1/FVC ratio, a measure of airflow obstruction. Fifteen patients had preserved lung function, defined by an FEV1/FVC ratio above the fifth percentile, while 13 had reduced lung function, with ratios below the fifth percentile.
Immune cell levels declined after treatment
Across the study population, neutrophil counts decreased significantly after both six and 12 months of Kaftrio treatment. The reductions were greatest in patients with preserved lung function, whereas changes among those with more advanced lung disease did not reach statistical significance when individual time points were compared.
Monocyte counts also declined significantly in both groups. However, patients with preserved lung function experienced earlier and more pronounced reductions. Among those with reduced lung function, monocyte levels were significantly lower after one year of treatment but not after six months.
No significant changes were observed in other white blood cell populations. Basophil counts remained higher in patients with poorer baseline lung function, although the clinical significance of this finding is unclear. The researchers suggested it may reflect more advanced airway inflammation.
Fewer exacerbations and less P. aeruginosa
After one year of treatment, participants experienced fewer pulmonary exacerbations requiring intravenous antibiotics. However, because of the study’s small sample size, the researchers could not determine whether this reduction was statistically significant. Notably, no exacerbations occurred during follow-up among patients with preserved baseline lung function.
The proportion of participants with detectable P. aeruginosa in sputum or throat swabs also fell, decreasing from 32.1% before treatment to 17.9% after both six and 12 months of Kaftrio therapy. Once again, the greatest reductions were observed in patients with better lung function at the start of treatment.
Looking ahead
Overall, the findings support previous evidence that CFTR modulators provide both clinical and anti-inflammatory benefits in cystic fibrosis. According to the researchers, the reductions in neutrophil and monocyte levels may reflect decreased chronic systemic inflammation resulting from improved CFTR function and enhanced mucociliary clearance, the lungs’ natural mechanism for removing mucus and pathogens.
The authors emphasized that larger, prospective studies with longer follow-up are needed to better understand the long-term effects of Kaftrio on immune function and chronic airway infections across different stages of CF lung disease.
Contact
Łukasz Pyzia
University of Rzeszów