Trikafta May Be Safe and Effective for Liver Transplant Patients

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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People with cystic fibrosis (CF) who had a liver transplant can be safely started on Trikafta (elexacaftor/tezacaftor/ivacaftor), a small study suggests.

For most patients in the study, Trikafta’s use resulted in an easing of symptoms, better quality of life, and healthier body weight and lung function.

Doctors with the CF and transplant teams should work together in closely monitoring a patient’s progress to “ensure safe initiation and balance overall expectations of treatment,” the study’s researchers wrote.

The study, “The use of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis post-liver transplant: a case series,” was published in the journal Pediatric Pulmonology by researchers in the U.S.

Trikafta, marketed by Vertex Pharmaceuticals, is approved in the U.S. to treat patients ages 6 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or another responsive mutation. It works by targeting the defective CFTR protein and helping it to work properly.

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In Canada and in the European Union (where it’s sold as Kaftrio), the triple-combination therapy is approved for this patient group starting at age 12. A branch of the European Medicines Agency recently recommended Kaftrio be extended to patients ages 6 and older, and Health Canada is considering a similar extension.

Regulatory approval was based on positive results from clinical trials showing its efficacy and safety. However, liver damage can occur as a side effect of Trikafta’s use, and patients who have or had liver problems are advised to talk with their doctor before starting with it. For those getting a solid organ transplant, possible problems include a worsening of liver function and drug–drug interactions with immunosuppressants, which must be taken to prevent the immune system from attacking the transplant.

Despite the risks, Trikafta may offer benefits to some CF patients who had a lung transplant. However, “there are no recommendations provided for CFTR modulator use” with patients undergoing a liver transplant, the researchers wrote.

The team looked at the medical records of six male and four female patients who had a liver transplant at six different centers. Their median age was 22.1, ranging from 14 to 43.4 years.

Upon treatment with Trikafta, changes in liver function occurred in all 10 patients and led to treatment discontinuation in two (20%). The remaining eight (80%) received a reduced or full dose of Trikafta for a mean of 10.4 months, ranging from seven to 12 months. For those started on a lower doses, dosing was gradually escalated based on liver function test results.

Eight (80%) of the patients were on tacrolimus, an immunosuppressant. Trikafta’s initiation in seven of them resulted in an increase of tacrolimus’ trough level — the lowest level reached by a medication before its next dose is administered — reaching toxic levels in one person. As a result, the dose of tacrolimus had to be adjusted in six patients.

“Initiation [of Trikafta] at lower doses with a slow titration may reduce the degree of fluctuation with tacrolimus trough concentrations and toxicity,” the researchers wrote.

Other reported side effects were fatigue and changes in stool frequency. A 22-year-old woman also had a seizure that led to Trikafta being stopped for one week, then restarted without incident.

Lung function, assessed based on a test that measures the amount of air that can be forcibly exhaled in one second (FEV1), was maintained or improved for all patients with available data.

Improvements in body mass index or BMI, a measure of weight in relation to height, as well as  quality of life and the ability to carry on with daily activities were also noted.

Overall, study findings suggest that Trikafta may have clinical benefits in patients with CF and a liver transplant.

However, “risks are still present and should be weighed heavily against the potential benefits for each individual patient,” the researchers wrote, adding that “early and close therapeutic drug monitoring of immunosuppression is important to ensure safety and efficacy of the regimen.”