CF patients show higher nasal nitric oxide levels with Trikafta
Low levels of biomarker have been linked with sinus inflammation
Treatment with Trikafta (ivacaftor/tezacaftor/elexacaftor) eases nose and sinus symptoms in eligible patients with cystic fibrosis (CF), and the improvement in nasal symptoms is accompanied by an increase in nasal nitric oxide (nNO), a biomarker.
The findings suggest “nNO could be used as an objective, noninvasive outcome measure for CF sinonasal [nose-and-sinus] disease,” researchers wrote in “Elexacaftor/tezacaftor/ivacaftor improves nasal nitric oxide in patients with cystic fibrosis,” which was published in the Journal of Cystic Fibrosis.
Trikafta is a combination therapy of three CFTR modulators, molecules that can boost the function of the defective CFTR protein in people with CF caused by specific mutations. It was approved based on clinical trial data that showed it could improve lung function with CF. Since its introduction, several reports have suggested it can also help ease sinonasal symptoms, such as chronic congestion, which is common with CF.
nNO is a signaling molecule that helps coordinate blood flow and nasal secretions. Research has shown nNO levels tend to be lower in people with CF, which has been linked with chronic sinus inflammation.
Changes to nNO levels with Trikafta
Here, scientists in Germany studied 25 people with CF, ranging in age from 2-43, who started on Trikafta to examine how the biomarker changes with treatment. “The aim of this study was to investigate the effect of [Trikafta] on nNO in [people with CF],” they wrote. The study included seven people with CF who weren’t eligible for Trikafta along with 32 people without CF who served as controls.
Other biomarkers and nNO were assessed before Trikafta was started and again after at least three months on the CFTR modulator therapy. The controls were also assessed at two points in time.
At the start of the study, nNO levels were significantly lower in CF patients than in people without the disease, which is consistent with previous research. In patients who weren’t eligible for Trikafta and those without CF, nNO levels remained steady over time, but they increased significantly for CF patients who started Trikafta to levels near that of participants without the disease.
“We showed that nNO increased significantly after several months of treatment with [Trikafta] to values within the normal range,” the researchers wrote.
About half the Trikafta-treated patients had reported sinonasal symptoms before starting the therapy. Most (75%) said their sinonasal symptoms were less severe after starting Trikafta, and none reported new symptoms.
The findings support the idea that nNO could be a useful biomarker of nose health in CF, though the researchers emphasized that their study was small and more research was needed.
Consistent with previous studies, treatment with Trikafta led to gains in markers of lung function. Still, statistical tests failed to find any associations between nNO levels and lung function improvements.
“We were not able to find a correlation between the improvement in nNO and lung function parameters,” the researchers wrote. Trikafta may have variable effects on different parts of the respiratory tract in different individual patients, the data suggest.
The study was part of a larger clinical trial (NCT04732910) that four university clinics in Germany are conducting to better understand how CFTR modulators affect disease biomarkers in CF. The trial is still recruiting participants at Charité – Universitätsmedizin Berlin, Hannover Medical School, Heidelberg University, and Justus-Liebig-University Giessen.
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