Treatment with Kaftrio may help ease sinus disease in CF children

MRI scans show fewer signs of disease with therapy, sold in US as Trikafta

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Treatment with Kaftrio (elexacaftor/tezacaftor/ivacaftor), sold in the U.S. as Trikafta, reduced signs of sinus disease, as seen on MRI scans, among children with cystic fibrosis (CF), according to new research from Germany.

Improvements were seen on the children’s imaging scans regardless of whether they had never before used a CFTR modulator therapy or had been previously treated with Orkambi (lumacaftor/ivacaftor), a similar combination medication.

In addition to demonstrating that Kaftrio can ease sinus abnormalities, the findings “support the role of MRI for comprehensive monitoring of [sinus] disease severity and response to therapy in children with CF,” the researchers wrote.

Titled “Elexacaftor/tezacaftor/ivacaftor improves chronic rhinosinusitis detected by magnetic resonance imaging in children with cystic fibrosis on long-term therapy with lumacaftor/ivacaftor,” the study detailing the research results was published in the Journal of Cystic Fibrosis.

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In CF, mucus can accumulate in the paranasal sinuses, or the the air-filled spaces in the skull. This causes ongoing sinus inflammation and infection, a condition known as chronic rhinosinusitis (CRS), or more commonly, a sinus infection.

For patients, sinus disease is characterized by structural changes in the sinuses that cause pain, swelling, and breathing problems. MRI imaging studies of the sinuses indicate that children with cystic fibrosis experience CRS starting early in infancy — and that it progresses in frequency and severity into childhood.

Vertex Pharmaceuticals markets both Kaftrio and Orkambi. The two approved CFTR modulator therapies are able to simultaneously target multiple CF symptoms by addressing the disease’s underlying mechanism — a faulty or deficient CFTR protein.

Among numerous demonstrated benefits, the more recently approved triple therapy Kaftrio has been shown to ease sinus and nasal symptoms in CF patients. It’s also been shown to reduce signs of CRS on CT scans and to prevent the need for sinus surgeries.

To learn more about the course of CF following newborn screening for the disease, researchers from Heidelberg University had been conducting an observational study (NCT02270476) that tracked these children during childhood. Now, a team of scientists from institutions in Heidelberg and Berlin used that data and other information to assess the impact of early Kaftrio treatment on CRS-related sinus abnormalities assessed via MRI scans.

Their analysis involved 30 school-aged children with CF who started on Kaftrio at the researchers’ hospital in Germany. All had at least one F508del mutation — the most common type of CF-causing mutation — in their CFTR gene.

Among them, 16 had never received a CFTR modulator — making them treatment naïve — and 14 had previously been on Orkambi. All received additional mucus-clearing treatments while on Kaftrio, such as saline nasal irrigation or nasal steroids.

Prior to starting on Kaftrio, the children underwent two MRI scans. For those who had been on Orkambi, this involved one treatment-naïve scan and one at least nine months after starting on the medication.

For treatment-naïve patients, sinus features remained relatively stable between the first two scans, whereas those who had taken Orkambi experienced some improvements.

Kaftrio treatment then was started, and a third MRI scan was taken — at a mean of 4.7 months later for treatment-naïve patients, and 6.9 months later for those previously given Orkambi.

For all of the children, the results indicated improvements in sinus deformities after starting Kaftrio.

Altogether, a significant 9.6-point decrease in the CRS-MRI sum score were observed. This is a composite measure of sinus abnormalities in which higher scores indicate more substantial CRS.

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Data show Kaftrio may be more effective than Orkambi for sinus disease

Certain sinus features also were found to be significantly improved among the children. For example, the width of the maxillary sinuses that lie to the sides of the nose was significantly lowered, which the scientists noted reflects a reduction in certain structural deformities caused by CRS.

The prevalence of mucopyoceles, a type of lesion or tissue damage in the sinuses that can drive symptoms such as headache and infection, also were significantly decreased after the start of treatment.

Improvements were similar in children who had or had not been on Orkambi previously.

According to the researchers, these findings demonstrate that Kaftrio may be more effective than Orkambi for reducing CRS. While patients saw some gains on Orkambi, they continued to further improve, rather than simply stabilizing, once they switched to Kaftrio, the team noted.

[These findings] further support comprehensive … sinus MRI [scans] as a sensitive non-invasive and radiation-free diagnostic tool for the detection of response to therapy of CF-related abnormalities of the upper airways.

Data were not collected related to how these structural changes in the sinuses might correlate with changes in inflammation or clinical symptoms of CRS.

“Further work will be needed to systematically assess the association between the CRS-MRI score and its abnormality subscores with clinical disease severity,” the researchers wrote.

Nevertheless, these findings support the use of sinus MRI “as a potential endpoint in clinical trials testing novel therapies for CRS in children with CF,” the team noted.

Moreover, the researchers concluded that the results “further support comprehensive … sinus MRI [scans] as a sensitive non-invasive and radiation-free diagnostic tool for the detection of response to therapy of CF-related abnormalities of the upper airways.”