Trikafta seen to ease sinus disease in CF, but most still affected: Study
Clinical trials with controls now needed to test therapy's efficacy
A year of treatment with Trikafta (elexacaftor/tezacaftor/ivacaftor) significantly reduces recurrent nose and sinus inflammation — called chronic rhinosinusitis, or CRS — in people with cystic fibrosis (CF), though most patients still exhibit signs of severe sinus disease.
These are the findings of a new U.S. study that, similar to previous research, also showed that Vertex Pharmaceuticals‘ approved therapy was associated with improved lung function, weight gain, and fewer lung infections.
Now, the researchers say, clinical trials “with appropriate control groups are required to assess the efficacy of this therapy on chronic sinus disease in this population.”
The study, “Elexacaftor-Tezacaftor-Ivacaftor Therapy for Chronic Sinus Disease in Cystic Fibrosis,” was published in JAMA Otolaryngology – Head & Neck Surgery.
Investigating the effects of Trikafta on sinus disease over 1 year
Mutations in the CFTR gene, leading to a faulty or missing CFTR protein, are the cause of CF. Consequently, thick and sticky mucus builds up in the body’s organs.
Lung manifestations, including chronic bacterial infections and progressive loss of lung function, are hallmark CF symptoms, but this mucus buildup also can affect the upper airways.
About half of CF patients experience chronic rhinosinusitis, or CRS for short, wherein the mucus membranes in the sinuses become infected and/or inflamed, leading to symptoms such as swelling, face pain, headache, and breathing or smell issues. Such symptoms have been shown to have a negative impact on patients’ life quality.
CFTR modulator therapies, which have become available over about the last decade, work to increase the protein’s function, thereby preventing mucus accumulation and easing CF symptoms. Trikafta, a triple combination CFTR modulator approved in the U.S. since 2019, is considered highly effective for improving lung function in people with CF.
However, the effects of CFTR modulators like Trikafta on symptoms outside of the lungs — including chronic sinus issues — are still being investigated.
Now, a trio of researchers at the Nationwide Children’s Hospital, in Columbus, Ohio, evaluated CRS changes after one year of Trikafta treatment among 64 CF patients seen at their hospital. The study was conducted from October 2019 to July 2021.
The participants, in all 39 females and 25 males, had a median age of 18.5 years — with 37.5% younger than 18. All were white individuals.
CRS severity was evaluated using a CT scan. These scans were collected within a month of starting Trikafta — the study’s baseline, or starting point — and again within a month after completing a year of treatment.
Three independent experts used two different scoring systems, called the Lund-Mackay score and the Sheikh-Lind score, to evaluate the results.
2 testing scales, one not CF-specific, found easy to use in clinical settings
The Lund-Mackay system, while simple to administer and commonly used, is not specific to CF. The more recently developed Sheikh-Lind scale “has been validated as more CF specific,” the researchers wrote, adding that it assesses specific features seen in CF patients that are not seen with other causes of CRS.
Still, “both the Lund-Mackay and Sheikh-Lind systems are easy to use in clinical settings and can be reproducibly implemented by clinicians, surgeons, and radiologists,” the team wrote.
The results showed that CRS severity decreased after a year on Trikafta for most participants, reflected as a reduction in scores on either of the two scoring systems.
[Trikafta treatment in CF patients] was associated with a decrease in CRS [chronic rhinosinusitis] based on sinus CT scans using 2 scoring systems and was also associated with improvements in clinical outcomes and reductions in bacterial colonization.
Using the Lund-Mackay system, the median score dropped from 5.8 at baseline to 3.3 after a year of treatment. Likewise, median Sheikh-Lind scores were lowered from 3.8 at baseline to 2.2 with treatment.
According to the Lund-Mackay system, a mean score above four reflects a need for sinus surgery. At the start of treatment, 63 participants (98.4%) met this criterion. That number decreased to 52 people (81.3%) after a year.
Moreover, a Lund-Mackay score greater than five is associated with severe sinus disease. At baseline, all but one patient (98.4%) met this criterion, while after one year of treatment 75% of participants — 48 in total — scored this high.
Despite score reductions, “most participants still had scores for both systems that indicated severe sinus disease,” the researchers wrote.
During the year of treatment, no patient underwent sinus surgery or required intravenous or into-the-vein antibiotics for acute bouts of CRS.
In addition, and as also reported in previous studies, Trikafta treatment was associated with decreases in sweat chloride levels and fewer lung infections. In turn, healthy weight gain and improvements in lung function were found.
Overall, Trikafta treatment in CF patients “was associated with a decrease in CRS based on sinus CT scans using 2 scoring systems and was also associated with improvements in clinical outcomes and reductions in bacterial colonization,” the researchers wrote.
The team emphasized, however, that appropriately-controlled clinical trials are still needed to definitively determine the effects of Trikafta on sinus symptoms.