Advanced lung disease patients benefit from long-term Trikafta
Real-world analysis reviewed outcomes for 64 adults with cystic fibrosis
Long-term treatment with Trikafta (elexacaftor/tezacaftor/ivacaftor) led to significant gains in lung function and nutritional status for cystic fibrosis (CF) patients with advanced lung disease, a real-world analysis shows.
The improvements weren’t as large as those seen in patients with milder lung disease, but the findings demonstrate the CFTR modulator therapy may still significantly benefit people with greater lung involvement.
The study, “Long-Term Clinical Efficacy of Elexacaftor-Tezacaftor-Ivacaftor in People with Cystic Fibrosis & Pre-existing Advanced Lung Disease at Treatment Initiation,” was published in CHEST Pulmonary.
In CF, the CFTR protein that’s responsible for moving chloride into and out of cells is absent or dysfunctional, allowing thick, sticky mucus to accumulate throughout the body. Trikafta is a triple combination CFTR modulator that’s designed to help defective CFTR channels work more effectively to ease CF symptoms.
Clinical trials leading to Trikafta’s approval showed substantial benefits from the modulator therapy, including improved lung function, reductions in pulmonary exacerbations, which are acute bouts of worsening lung function, and better nutritional status that was reflected by increases in body mass index (BMI).
These trials generally only included patients with mild or moderate lung disease and excluded those with advanced lung disease, or lung function less than 40% of normal, however, leaving the therapy’s long-term benefits in more advanced disease to be unraveled in real-world studies. Here, researchers retrospectively analyzed outcomes among 64 adults with advanced lung disease treated with Trikafta at three large U.S. centers.
Significant gains with Trikafta
The researchers previously reported the patients exhibited a 7.9% improvement in lung function after three months on Trikafta over the pre-treatment period, or baseline, and here report one- and two-year outcomes from the same group that show lung function significantly improved by 7.56% after a year on Trikafta over the baseline. After two years, lung function improved by 6.74% compared with baseline. Seven people (11%) saw a decline in lung function by a mean of 3.7% over two years.
The subset of patients with baseline lung function of 30% or less also saw significant improvements, by 4% after a year and by 2.5% after two years, although these gains were smaller than those seen in the larger group.
BMI also increased significantly after one and two years on Trikafta, and the annual rate of pulmonary exacerbations significantly decreased. People on Trikafta had close to two fewer exacerbations after one and two years of treatment, on average.
Overall, “these clinical effects on lung function, BMI, and annual pulmonary exacerbation rate are similar to those seen in [people with CF on Trikafta] who had mild to moderate lung disease, though the changes … are less robust,” the researchers wrote. “These results may … suggest [Trikafta] changes the trajectory of respiratory progression in patients with preexisting [advanced cystic fibrosis lung disease] at the time of treatment initiation.”
When they started Trikafta, all 64 participants met the criteria for discussing or being referred for a lung transplant and 50 people had been referred for one. Of those 50, only one patient received a lung transplant within a few weeks of starting Trikafta.
Using Trikafta might make it more difficult to determine which patients need to be referred for lung transplants, as existing guidelines were developed before the therapy became available, the researchers said.
“We recommend that a multidisciplinary discussion with the CF team, palliative care, and lung transplant center should be considered regarding referral and listing status,” wrote the researchers, who said more clinical studies are needed to establish the long-term effects of Trikafta in advanced CF lung disease.
“Additional studies that should also be considered include investigating the mechanisms underlying the observed treatment effects, exploring predictors of response to [Trikafta] therapy, and evaluating the cost-effectiveness of [Trikafta] in people with CF and [advanced lung disease],” they wrote.
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