#NACFC2021 – Trikafta May Benefit Some Lung Transplant Recipients
Treatment with Trikafta may improve nutritional status or lessen anemia among some people with cystic fibrosis (CF) who have received a lung transplant, but more research is needed to understand the potential benefits — and risks — of using the triple-combination medication in this particular patient population.
That’s according to data discussed at the 2021 North American Cystic Fibrosis Conference (NACFC), held virtually Nov. 2–5, in an oral presentation titled “Use of elexacaftor/tezacaftor/ivacaftor among CF lung transplant recipients.”
Trikafta, an oral therapy made by Vertex Pharmaceuticals, was first approved in the U.S. in 2019. Treatment with the CFTR modulator therapy — a next-generation combo of elexacaftor, tezacaftor, and ivacaftor, sometimes called ETI — has been shown to improve lung function and nutritional status for people with CF caused by specific mutations.
There is little data on Trikafta use among people with CF who have had a lung transplant. However, there is reason to think that at least some of these patients may benefit from such treatment, researchers say.
Trikafta “does not only affect the lungs, but has the potential to improve the multi-system clinical manifestations of CF, including sinus disease, malnutrition, diabetes, and [digestive] symptoms,” Kathleen J. Ramos, MD, of the University of Washington, said at NACFC.
Ramos and other scientists conducted an analysis of health records from 14 CF centers in North America, from October 2019 through September 2020, looking for cystic fibrosis patients who had received lung transplants and were prescribed Trikafta.
“The inclusion criterion was simple,” Ramos said. “You just needed to be a CF lung transplant recipient prescribed [Trikafta] after lung transplant.”
She noted that the analysis included all patients prescribed the therapy — not just those who actually took it — so as to identify individuals who had difficulty getting access to treatment.
“There was a lot of … variability from program to program when it came to prescribing [Trikafta] after lung transplant,” Ramos said. Specifically, at three centers, no lung transplant recipients were prescribed Trikafta. At the remaining 11 centers, rates of Trikafta prescription for transplant recipients ranged from 1% to 35%.
Across the centers, a total of 94 lung transplant recipients were prescribed the combo therapy — 13% of the 734 total transplant recipients. Of these patients, 90 actually started taking the medication. Their median age was 37, 57% were female, and the median time from lung transplant to the prescription of Trikafta was nearly five years.
The key reason for prescribing Trikafta was sinus disease; other common reasons included digestive symptoms and poor nutrition. Of note, in 42% of cases, the patient wanting to try the treatment was a documented factor in deciding to prescribe it.
Ramos noted that one patient was prescribed Trikafta, but did not take it, because the person’s insurer, a private insurance company, denied coverage of the medication. For the remaining 93 patients, their insurers “said yes to this prescription,” Ramos said.
Of the remaining three patients who didn’t start on treatment, the main reason was not wanting to go to the hospital to do required bloodwork during the COVID-19 pandemic.
Medication discontinuation did become a factor during the study, despite the large number of patients who had specifically sought to try Trikafta.
Of the 90 lung transplant recipients who started taking the therapy, 40 (44%) stopped, and most remained off Trikafta for the duration of the studied period. The median time from prescription to stopping treatment was about two months. The most common reasons for stopping the therapy were digestive side effects, specifically nausea, diarrhea, and abdominal pain.
“Nearly 100 CF lung transplant recipients have been prescribed [Trikafta], but one-third stopped and remained off of [Trikafta] due to side effects or a lack of perceived benefit,” Ramos said.
Only four cases have reported difficulty managing their immune-suppressing medications (given to prevent transplant rejection) after starting on Trikafta, according to Ramos. These individuals “just needed more frequent blood draws than usual” to ensure their immunosuppressants were working correctly, she said.
Analyses comparing clinical data before and after starting Trikafta indicated that the treatment increased levels of hemoglobin, the molecule used to carry oxygen through the blood. The average increase was statistically significant in the subset of patients with anemia, or low hemoglobin levels, prior to starting therapy.
The treatment also significantly decreased levels of hemoglobin A1c, a sugar-attached form of this protein that’s associated with diabetes, which was particularly pronounced in diabetic patients.
After starting on Trikafta, the number of treatments with antibiotics decreased, indicating fewer infections, and patients tended to gain weight, a sign of improving nutritional status. Of note, malnutrition has long been an issue for CF patients.
Ramos noted that, for many of these analyses, there was limited data available, because of logistical problems caused by the pandemic, for the time period during which patients were on Trikafta.
Collectively, the data show that, “for some patients, the effects [of Trikafta] were significant,” Ramos concluded. However, “there are a lot of side effects of [Trikafta] in this population,” which makes “unclear” its benefits relative to its costs.
“Further prospective study is warranted to determine whether [Trikafta] can … improve outcomes for individuals with CF and lung transplant,” she said.
Editor’s note: The Cystic Fibrosis News Today team is providing coverage of the virtual 2021 North American Cystic Fibrosis Conference (NACFC) Nov. 2-5. Go here to see the latest stories from the conference.
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