Trikafta use boosts quality of life in CF even without lung function gains
Real-world study finds improvements soon after starting treatment
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People with cystic fibrosis (CF) taking Trikafta usually report notable improvements in their quality of life — even if they don’t show substantial gains in objective measures of lung function — soon after starting treatment with the approved oral medication.
That’s according to a new real-world study, which also found these life quality improvements to be long-lasting.
The researchers suggested that these findings highlight the importance of overall quality of life, not just lung health, in assessing outcomes for CF treatments like Trikafta.
“Respiratory and non-respiratory improvements in patient-reported outcomes are seen even in the absence of objective increases in lung function, emphasizing the importance of considering a broad spectrum of [disease experiences] when evaluating improvements with [Trikafta] therapy,” the researchers wrote, noting that there was “no evidence of a difference between groups” based on function gains.
Additionally, the team noted that “our real-world data involving a large [group] of [people with] CF demonstrate that HRQoL [health-related quality of life] improvements are sustained across multiple domains.”
The study, “Real-World Impact of Elexacaftor/Tezacaftor/Ivacaftor on Health-Related Quality of Life in Adults with Cystic Fibrosis: A 12-Month Multicenter Cohort Study,” was published in the journal Respiratory Medicine.
A genetic condition, CF is caused by mutations that disrupt the production or activity of CFTR, a protein that’s critical for regulating mucus production. Lack of functional CFTR leads to the production of abnormally thick and sticky mucus, which builds up in the lungs and other organs to drive most CF symptoms.
Trikafta is a combination of three CFTR modulators (elexacaftor, tezacaftor, and ivacaftor), which are molecules that can increase the defective protein’s activity in people with CF caused by certain mutations. The therapy is widely approved for CF patients with amenable mutations, including the most common CF-causing mutation called F508del.
Does quality of life improve absent lung function gains?
Clinical trials have demonstrated that Trikafta is better than a placebo at improving standard measures of lung function such as ppFEV1 — fully, percent predicted forced expiratory volume in one second — which assesses how much air someone can blow out in a forceful breath. Trials have also suggested that CF patients tend to report improvements in quality of life after starting Trikafta.
But these studies have generally looked at averages. Each individual’s response to Trikafta may vary, and some people with CF don’t experience substantial improvements in lung function after starting the treatment.
In this study, a team of scientists in Canada wanted to see if such patients would still report improved life quality despite having minimal change on objective measures of lung function.
“While many individuals experience significant increases in percent predicted FEV1 (ppFEV1) following [Trikafta], some do not achieve notable lung function improvements. Although improvements in HRQoL have been observed broadly, studies have not specifically examined the experiences of those who do not have a notable change in lung function.
According to the scientists, “this gap represents an important opportunity to explore whether quality of life benefits extend to individuals whose lung function does not remarkably improve.”
With Trikafta use, that answer is yes, study finds.
The analysis involved data from 353 CF patients who were treated with Trikafta at clinics across Canada, with the majority specifically receiving care at the Toronto Adult CF clinic. Among the participants, 21% were on a prior modulator before starting Trikafta.
Over the course of a year after starting Trikafta, the patients regularly completed three standardized measures of quality of life. Two of these measures — the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and Cystic Fibrosis Quality-of-Life Evaluative Self-Administered Test (CF-QUEST) — are specifically designed to measure health-related quality of life in people with CF. The third test, called the Sino-Nasal Outcome Test or SNOT-22, specifically asks about symptoms affecting the nose and sinuses.
The results showed that average scores on all three standardized assessments improved significantly within a month of starting Trikafta, with the vast majority of patients reporting clinically meaningful improvements on each measure that lasted for the full year.
“Our study highlights a sustained improvement in HRQoL across all domains of the CFQ-R, CF-QUEST and SNOT-22 over 12 months following [Trikafta] initiation,” the researchers wrote, noting that this long-term impact on quality of life is “an aspect often not appreciated in studies with shorter time frames.”
The researchers then divided the patients into two groups: those whose ppFEV1 improved by at least 5% after starting Trikafta, called responders, and those whose lung function was largely unchanged, dubbed nonresponders. The researchers used statistical analyses to compare scores on each of the three tests between these two groups.
No significant differences were seen. In other words, across all three measures, both responders and nonresponders reported similar improvements in quality of life.
These data suggest that Trikafta may offer substantial benefits even for CF patients who don’t show improvements on standard lung function tests, according to the researchers. The team said these data underscore the importance of considering holistic quality of life, not just lung health, in CF care.
“To our knowledge, our study is the first to demonstrate that even in those with minimal or no improvement in lung function, initiation of [Trikafta] results in substantial improvements in HRQoL scores, highlighting the importance of considering additional measures when assessing clinical response to CFTR modulator treatment,” the scientists concluded.
Trikafta is sold by Vertex Pharmaceuticals, which was not involved with this study.
