Kaftrio (Trikafta) lowers bacteria levels in lungs over 1 year: Study
Lesser antiobiotic use, physiotherapy need also seen with triple combo therapy
After one year of treatment with Kaftrio, a triple combination of elexacaftor, tezacaftor, and ivacaftor marketed as Trikafta in the U.S., the number of harmful bacteria growing in the lungs of people with cystic fibrosis (CF) declined significantly, a French study reports.
“We observed a significant decrease in colonization prevalence by any CF pathogen after one year of treatment,” including “a decrease in prevalence of Pseudomonas aeruginosa chronic colonization and in the density of Pseudomonas aeruginosa,” researchers wrote in the study “One year of ETI reduces lung bacterial colonisation in adults with cystic fibrosis,” published in Scientific Reports.
While the findings add to evidence that Kaftrio may help to fend off lung infections, “further studies are needed to better understand the underlying mechanisms,” they added.
Triple combo therapy’s benefits known, but effects on bacteria unclear
CF is a genetic disease that causes thick mucus to build in the lungs, leading to breathing problems. Patients often develop difficult-to-treat lung infections caused by bacteria, which can worsen disease symptoms and affect their lives. Over time, treatments have focused on fighting these infections.
Vertex Pharmaceuticals’ Kaftrio targets the CFTR protein that is faulty in CF, helping it function better. The therapy has been shown to improve lung function and quality of life, but how it changes bacteria living in the lungs is still unclear.
“The impressive clinical effectiveness of [Kaftrio/Trikafta] on lung function raises the question of its microbiological repercussions on lung bacteriological colonization,” the researchers wrote.
Their study included 198 adults with CF, with a median age of 28.8 and mostly men (61%), who started treatment with Kaftrio between January 2020 and December 2021. Most patients (62%) had the F508del mutation, the most common genetic cause of CF, in both CFTR gene copies, and just over half (54%) switched from a previous CFTR modulator treatment, often Orkambi (ivacaftor/lumacaftor).
In the three years before treatment, the mean percentage of predicted forced expiratory volume in one second, a standard measure of lung health, had declined each year, falling from 65.4% to 63.8% and 60.1%. After a year on Kaftrio, it increased to 77.4%, an indication that these patients could breathe better.
The mean number of disease flares, periods when symptoms worsen suddenly, decreased from 2.8 per year to 0.7 over the treatment year. Patients also needed less physiotherapy, with weekly sessions falling from 3.8 to 2.2, and fewer were using inhaled antibiotics (a decline of 65% to 37%). Hospital stays also decreased, with 28% of patients needing hospitalization before starting on Kaftrio, compared with 3% after their year of treatment. The mean length of hospital stays also fell from 18 days to 11 days.
Decline with year of treatment in chronic P. aeruginosa colonization of lungs
Bacterial colonization — the name given to harmful bacteria that grow and live in the lungs, often without causing immediate symptoms but leading to infections over time — also “significantly decreased,” the researchers wrote. Sputum or phlegm samples showed that nearly all patients (99%, or 193 of 194 people in the study’s first pretreatment year) tested positive for at least one species of bacteria before treatment, while 90% (161 patients) continued to show colonization after a year of Kaftrio’s use.
Chronic colonization with Pseudomonas aeruginosa, a common cause of lung infections in CF, decreased from 65% to 51%, and no new infections occurred. Younger patients and those with less severe lung damage appeared to experience greater improvements, but this finding was not statistically significant.
“Our study confirms the decrease both in sputum bacterial density and in the prevalence of lung colonisation by most CF pathogens, in association with clinical respiratory improvement in adult [CF patients] after one year of treatment with [Kaftrio],” the researchers wrote.
“These microbiological changes highlight the need for CF medical care guidelines updating for sputum monitoring and antibiotic strategies,” they added, noting that more research is needed to understand how this triple combination therapy brings about the changes reported.
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