What leads to early Kaftrio use in CF? Researchers launch survey to find out.
Respiratory symptoms found to drive treatment start for adults
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Respiratory symptoms are key drivers for starting Kaftrio (elexacaftor/tezacaftor/ivacaftor) among adults with cystic fibrosis (CF) who have stable, near-normal breathing ability, known as preserved lung function, a survey study in Europe has found.
In surveying CF centers across the continent, the research team found that clinicians were more likely to start Kaftrio treatment in certain adults based on signs such as prior infections, changes to lung structure found on CT scans, and nutritional status. These healthcare professionals, however, showed caution in initiating such treatment for patients older than 50, as well as those who were overweight or had a history of mental health issues, the data showed.
Ultimately, the scientists found, “a key [factor] influencing [Kaftrio] initiation decisions was the presence of respiratory symptoms.”
According to the team, the findings highlight the “absence of clear clinical guidance” in prescribing the approved therapy, sold as Trikafta in the U.S., among people with CF in Europe.
“In the absence of evidence-based data and formal recommendations for this specific population, treatment decisions are largely guided by expert opinion and the clinical judgment of individual centres,” the researchers wrote.
Their study, “Determinants of early Elexacaftor-Tezacaftor-Ivacaftor use in adults with cystic fibrosis and preserved lung function: insights from a European multicenter survey,” was published in the Journal of Cystic Fibrosis.
CF is caused by genetic mutations that result in the loss or dysfunction of the CFTR protein, which helps regulate the balance of salt and water in the body. This leads to the accumulation of thick, sticky mucus in various organs, particularly the lungs.
Kaftrio is a CFTR modulator that’s now approved in more than 30 countries. Its use has led to significant improvements in lung function, among other benefits, for people with CF. However, there is limited evidence for this treatment’s use in patients with preserved lung function, particularly those with a percent predicted forced expiratory volume in one second (ppFEV1) higher than 90%. ppFEV1 measures the amount of air that can be forcefully exhaled after a deep breath, compared with healthy individuals with similar characteristics.
Investigating the decision to start Kaftrio treatment
To identify factors influencing the decision to start Kaftrio in people with the genetic condition, researchers in Europe conducted a web-based survey study across 23 CF centers. Slightly more than half of respondents (57%) were women, and most centers (65%) followed at least 200 CF patients.
The CF centers generally favored an early start on Kaftrio for eligible adults, the researchers found. In most cases, the decision to start treatment was influenced by individual clinical characteristics, particularly respiratory symptoms, affecting 61%, and nutritional status, noted for 57%. However, about one-third of respondents disagreed that such individual factors should influence the timing of Kaftrio initiation, the survey found.
The most significant factors that encouraged starting treatment were the prior detection of the bacteria Pseudomonas aeruginosa (78%), which is a common cause of lung infections in individuals with CF. Other indicators supporting the treatment in a similar percentage of centers included having bacteria in sputum and the detection of non-tuberculous mycobacteria.
Having been given at least one antibiotic course in the previous year also was a factor supporting treatment start, the data showed.
CF-related abnormalities on chest CT scan prompted treatment by 87% of responders, versus 78% if abnormalities were detected on chest radiograph, the survey results showed. Among the most relevant CT findings were airway widening and thickening, as well as mucus plugging.
Further, the decision to initiate Kaftrio in individuals with at least one F508del mutation, the most common CF-causing mutation, depended on the second CFTR gene copy, the researchers noted. In general, a second copy carrying a mutation for which the treatment is approved in the U.S. meant Kaftrio would be encouraged or strongly encouraged, the data showed.
Common CF-related conditions also had an impact, as chronic inflammation of the sinuses, CF-related diabetes (both 78%), and being underweight (83%) mostly made the clinicians support Kafrio therapy. Slightly less than one-third of clinicians were dissuaded from prescribing the treatment in overweight or obese patients, and 43% for those with a history mental health issues.
Use of other treatments found to influence clinician decisions
Previous use of other CFTR modulators also influenced the decision to start Kaftrio, the researchers found.
While more than three-quarters of respondents (78%) tended to prescribe Kaftrio when prior CFTR modulators were effective, no such general agreement was found when those treatments were not effective.
Other factors playing a significant role included patients’ willingness to start therapy, chronic cough, and sputum production (87% each). A desire for pregnancy divided opinions, with 35% each considering it encouraged or discouraged treatment, the data showed.
Patients’ age and sex did not appear to significantly influence the decision to initiate Kaftrio, although 22% of clinicians reported greater caution for starting the treatment in patients older than 50. Additionally, 65% avoided prescribing it to patients with a CFTR-related disorder — conditions associated with CFTR gene mutations that do not meet CF diagnostic criteria.
These findings show, overall, the need for clear guidelines for the medication’s use, the researchers concluded.
“Although several disease markers more consistently support the decision to initiate [Kaftrio] in individuals with preserved lung function, the absence of clear clinical guidance contributes to heterogeneous prescribing practices across centres,” the researchers wrote. They also highlighted that further studies are needed to “clarify the long-term outcomes of [Kaftrio] in this population.”
