Lung function decline consistently slows over 5 years with Kalydeco
Researchers compared CF patients who did, didn't receive treatment
Lung function decline slowed consistently over five years with Kalydeco (ivacaftor) treatment in adults and children with cystic fibrosis (CF), a real-world study in the U.S. shows.
“Overall, these results expand on those from prior studies and show that [Kalydeco] has a meaningful and sustained impact on reducing the rate of lung function decline in people with CF in a real-world setting,” wrote the researchers, who noted the effect was more pronounced in adults.
The study, “A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis,” was published in Pulmonary Therapy.
CF is caused by mutations in the CFTR gene, which encodes a protein essential for producing watery mucus in the airways and other organs. When the protein is faulty or missing, thick, sticky mucus builds up, causing respiratory and other symptoms.
Comparing patients who did, didn’t receive Kalydeco
Kalydeco is a CFTR modulator that enhances the function of the CFTR protein. It’s approved in the U.S. for CF patients with at least one CF-causing mutation that responds to the treatment. It was shown to slow lung function decline and reduce the risk of severe clinical outcomes in CF.
“However, additional long-term data from real-world studies are needed to understand the durability of this effect,” wrote researchers who compared 548 CF patients treated with Kalydeco against 541 patients not treated with a CFTR modulator and not eligible to receive Kalydeco, to estimate change in lung function over five years. All the control group participants had a CFTR gene copy with a F508del mutation, the most common CF-causing change in CFTR, and another copy with a minimal function mutation, or a mutation where the resulting CFTR protein works minimally.
Data were obtained from the CF Foundation Patient Registry. The analysis was restricted to data through the end of 2019 when the most recent CFTR modulator Trikafta (elexacaftor/tezacaftor/ivacaftor) was approved in the U.S. This was because many participants were expected to start Trikafta once it became available.
The groups had a mean age of around 18 and a mean percent predicted forced expiratory volume in one second (ppFEV1) of 81%-82%. ppFEV1 is a measure of lung function that evaluates the maximum amount of air that can be forcibly exhaled in a second.
The annualized rate of ppFEV1 decrease was 1.23 over five years in patients on Kalydeco compared with 2.03 in nontreated patients, corresponding to a 39% lower decline. This was consistent with findings in shorter follow-ups of two (28% lower decline), three (33%), and four years (36%).
“Therefore, the relative reduction in the rate of lung function decline observed in the [Kalydeco]-treated cohort compared with the comparator cohort was maintained over [five] years of follow-up,” the researchers wrote.
These effects were similar when analyzing adults and children separately, despite a higher relative reduction in adults, 47% versus 34%.
“Overall, the results from our study corroborate results observed in previous studies, strengthening the evidence that treatment with [Kalydeco] may change the trajectory of CF,” wrote the researchers, who noted the study offers evidence that Kalydeco’s effects don’t diminish with time.
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