Kaftrio benefits CF patients with advanced disease: Real-world study

FEV1%, FVC% improved after 2.5 years; infections, antibiotic use decreased

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Kaftrio improved lung function for up to 2.5 years in cystic fibrosis (CF) patients with advanced disease who had early access to the medication in Spain, according to a real-world study.

Taking Kaftrio, a triple combination of elexacaftor, tezacaftor, and ivacaftor, also reduced the frequency of exacerbations, when symptoms worsen suddenly, and improved quality of life, while being generally safe and well tolerated.

The study, “Experience with Tezacaftor/Ivacaftor/Elexacaftor in Patients with Cystic Fibrosis and Advanced Disease,” was published in Archivos de Bronconeumologia.

Vertex Pharmaceuticals’ triple combination is sold as Trikafta in the U.S., where it was approved in 2019. A so-called CFTR modulator, it works both as a corrector, helping the faulty CFTR protein fold correctly, and as a potentiator, aiding its efficiency.

Available initially in Europe to patients with advanced disease under a compassionate use program, Kaftrio had a wider rollout when it was approved in mid 2020 for all patients ages 12 and older who carried one or two copies of the CF-causing F508del mutation.

Its indication was later expanded for more mutations and a broader age range in the U.S. and Europe. Not many studies have examined how safe the medication is and how well it works over time, leading researchers in Spain to describe the experience of 114 patients with advanced disease who had access to Kaftrio before it was available on the market. They were followed for up to 30 months (about 2.5 years) at 16 CF units across the country.

Of them, 85 (74.6%) carried one copy of the F508del mutation and 29 (25.4%) carried two copies. Their mean age was 32.2 and more than half (51.8%) were men.

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A set of lungs are shown struggling to breathe.

Kaftrio effective in CF patients with advanced lung disease: Study

Gains with Kaftrio after 2.5 years

To have early access to Kaftrio, patients had to have a forced expiratory volume in 1 second (FEV1%) less than 40%. FEV1% is a measure of lung function and a FEV1% below 40% indicates advanced lung disease. The mean FEV1% of the group was even lower, at 37.5%.

After 2.5 years of treatment, the mean FEV1% improved significantly, to 48.7. Forced vital capacity (FVC%), another lung function measure, also increased significantly, from an average of 58.6 to 73.2.

Living with CF may mean difficulty maintaining a healthy weight. Before treatment, the mean body mass index (BMI), a measure of body fat based on weight and height, of the group was 20.5. After 2.5 years, it increased significantly to 22.3, indicating better nutrition.

People with CF are also at an increased risk of recurrent lung infections, with antibiotics being the usual treatment. Before treatment, more than half (60.5%) tested positive for Pseudomonas aeruginosa, a species of bacteria often found in CF lungs.

As early as after 1.5 years of treatment, no patient tested positive for P. aeruginosa. The proportion testing positive for other bacteria also decreased over 2.5 years.

Moreover, the number of cycles of antibiotics decreased from an average of 2.7 in the year before treatment to 0.8 a year after treatment if given by mouth and from 1.8 to 0.3 if given intravenously.

The number of exacerbations also decreased from an average of 3.9 in the year before treatment to 0.9 a year after, which translated into an overall improvement of quality of life for patients. Kaftrio didn’t seem to improve digestive symptoms, however.

Kaftrio also reduced the need for other treatments. For example, “oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list,” the researchers wrote.

The treatment was generally safe, with only a small number of patients having to stop it due to a temporary increase in the level of liver enzymes, a sign that the liver may be damaged.

The data showed Kaftrio “decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment … It is a safe and well-tolerated drug,” the researchers said, who recommended doing longer studies with more patients from different countries provided by CF registry data because only about a third of the patients were actually followed for 2.5 years or more.