Lung transplant rates for cystic fibrosis (CF) patients in the United States have fallen dramatically since the approval of Trikafta (elexacaftar/tezacaftar/ivacaftar), according to a study.
However, nearly half of patients who have had transplants in recent years took Trikafta before surgery, and a significant proportion of CF patients with advanced lung disease who were taking Trikafta died before undergoing a transplant.
The findings indicate that despite the recent availability of highly effective CFTR modulating therapies, lung transplantation is likely to remain an important option for patients who already have advanced lung disease.
the study, “Dramatic decline in lung transplants for cystic fibrosis in the United States” was published as a research paper in 2009. Chest Lungs.
In CF, the buildup of thick, sticky mucus in the lungs leads to infection, inflammation, and tissue damage, gradually impairing lung function. For patients with advanced lung disease, lung transplantation is an important and life-saving treatment option. Guidelines recommend that physicians discuss the benefits of transplantation with patients early and recommend transplant surgery for patients with very poor lung function.
Trikafta changes the landscape
The treatment landscape changed dramatically with the approval of Trikafta in 2019, as eligible patients' lung function began to improve significantly. Subsequent studies showed that patients who were previously eligible for transplant were taken off the waiting list, and transplant rates fell.
The study authors noted that it is currently less clear when transplantation is indicated for CF patients. To learn more, they looked at changes in transplant and mortality rates for CF patients in the United States since Trikafta was approved.
Lung transplant data from 2011 to 2022 were obtained from the public database of the United Network for Organ Sharing. Other clinical data were CF Foundation.
The total number of lung transplants performed in the United States for any reason has increased gradually, from 1,822 in 2011 to a peak of 2,714 in 2019. Transplant rates for CF patients in particular remained relatively stable over the study period, accounting for 9% to 13% of all transplants.
While overall U.S. transplant rates have remained stable since about 2020, CF transplant rates have fallen dramatically since late 2019, when Trikafta was approved. In 2022, CF patients accounted for just 1% of all transplants.
2020, 2021, 2022, the years immediately following Trikafta's approval — Of the 66, 42, and 39 CF patients who underwent first lung transplants, 42% to 49% were prescribed Trikafta each year before transplantation.
In 2011, 10.7% of CF patients whose lung function had dropped to 50% of normal (advanced lung disease) died without receiving a lung transplant, a rate that dropped to just 2.5% in 2022. Still, the number of people dying without a transplant increased relative to the number of lung transplants performed in that period.
“The reasons for this change are unclear but are likely multifactorial,” the researchers wrote.
A concern arising from the study is that the decision to refer a patient for lung transplant is “clouded by the dramatic improvements overall in CF patients.” [Trikafta]resulting in delayed or non-existent transplant referral,” the researchers wrote.
Of the 84 patients with advanced lung disease who died without receiving a transplant in 2020, just over one-third (39%) had been prescribed Trikafta before their death, taking it for an average of 217 days (nearly seven months). By 2022, 71% of these patients had been prescribed Trikafta, and the average time from first prescription to death was 825 days, or just over two years.
The scientists said the findings suggest that patients with advanced lung disease who start Trikafta may not necessarily see sufficient recovery of lung function to avoid transplantation. [lung transplant] will remain an important treatment option [people with CF] “For the time being,” they wrote.
The analysis was missing some data, including a lack of information on factors such as cause of death and transplant referral status for those who died without receiving a transplant, limiting interpretation of the results.
“Without more detailed data, [advanced lung disease] Ultimately necessary [lung transplant] in spite of [Trikafta] “Prescription,” the team concluded.
