Lung transplants for CF on decline since Trikafta: U.S. study
Transplants still important for those with advanced lung disease
Lung transplant rates among people with cystic fibrosis (CF) in the U.S. have declined dramatically since the approval of Trikafta (elexacaftor/tezacaftor/ivacaftor), a study found.
However, almost half of patients who received transplants in recent years were on Trikafta before their procedures. Moreover, a notable proportion of CF patients with advanced lung disease who were on Trikafta died without receiving a transplant.
The findings show that despite the recent availability of highly effective CFTR modulator therapies, lung transplants are likely still a critical option for patients who already have advanced lung disease.
The study, “A dramatic decline in lung transplantation for cystic fibrosis in the United States,” was published as a research letter in CHEST Pulmonary.
In CF, the accumulation of thick and sticky mucus in the lungs drives infections, inflammation, and tissue damage that contribute to progressively declining lung function. For patients with advanced lung disease, a lung transplant is an important and life-saving treatment option. Guidelines suggest that doctors have early discussions with their patients about the benefits of transplant and that patients with very low lung function be referred for the procedure.
Trikafta changes landscape
The treatment landscape changed dramatically in 2019, when Trikafta was approved and eligible patients started seeing substantial lung function improvements. Subsequent studies showed that patients previously indicated for transplant were being removed from waiting lists, and transplant rates went down.
It is now less clear when a transplant might be indicated for a CF patient, the study’s authors said. To learn more, they examined changes in transplant and mortality rates for CF patients in the U.S. since Trikafta’s approval.
Lung transplant data between 2011 and 2022 were obtained from a publicly available database from the United Network for Organ Sharing. Other clinical data were provided by the CF Foundation.
The total number of lung transplants in the U.S. performed for any reason gradually increased, rising from 1,822 in 2011 to a peak of 2,714 in 2019. Transplant rates in CF patients specifically were relatively stable across the study period, accounting for 9%-13% of all transplants.
While overall U.S. transplant rates have remained stable since about 2020, there was a dramatic decline in CF transplant rates starting in late 2019 when Trikafta was approved. In 2022, CF patients accounted for just 1% of all transplants.
In 2020, 2021, and 2022 — the years just after Trikafta was approved — 66, 42, and 39 CF patients, respectively, had a first lung transplant. Among them, 42%-49% each year had been prescribed Trikafta pre-transplant.
In 2011, 10.7% of CF patients with lung function up to 50% of normal (advanced lung disease) died without lung transplants. This rate decreased to just 2.5% in 2022. Still, the number of deaths without transplant increased relative to the number of lung transplants being performed in that window.
“The reasons for this change are unclear and likely multifactorial,” the researchers wrote.
A concern arising from the study is that the decision to refer patients for lung transplant “has been clouded by the dramatic improvements in the overall CF population since [Trikafta], leading to late or non-referral for transplant,” the researchers wrote.
Of the 84 people with advanced lung disease who died without transplant in 2020, a little over a third (39%) had a Trikafta prescription for a median of 217 days (about seven months) before they died. By 2022, 71% of such patients were prescribed Trikafta, with a median time to death from first prescription of 825 days, or a little over two years.
The scientists said the findings demonstrate that patients with advanced lung disease who start Trikafta might not necessarily see a reversal in lung function sufficient enough to avoid transplant. Therefore, “it seems very likely that [lung transplant] will remain an important treatment option for [people with CF] for the foreseeable future,” they wrote.
Some data were lacking from the analyses. A lack of information about factors including causes of death and transplant referral statuses for those who died without receiving one limited the interpretation of the results.
“More granular data is necessary to understand the reasons why people with [advanced lung disease] ultimately needed [lung transplant] despite [Trikafta] prescription,” the team concluded.
About the Author
