Everolimus and tacrolimus Combo Safe with Better Kidney Outcomes in Pediatric Heart Transplants: JAMA
USA: Researchers have found in a new study that among 6-month pediatric heart transplant survivors, everolimus with low-dose tacrolimus was as effective as tacrolimus with mycophenolate in preventing rejection, cardiac allograft vasculopathy (CAV), and chronic kidney disease (CKD) at 30 months. The everolimus regimen also appeared to be safe. It was associated with improved kidney function and a reduction in cytomegalovirus (CMV) infections.
The randomized clinical trial, published in JAMA, was conducted by Dr. Christopher S. Almond and colleagues from the Department of Pediatrics (Cardiology), Stanford University School of Medicine, Palo Alto, California.
The study aimed to evaluate whether combining everolimus with a reduced dose of tacrolimus could safely and effectively prevent major transplant complications when initiated six months after pediatric heart transplantation.
A total of 211 children who had survived at least six months after a heart transplant across 25 U.S. centers were enrolled between February 2018 and August 2020. The participants were randomly assigned to receive either everolimus with low-dose tacrolimus (107 children) or the standard regimen of tacrolimus with mycophenolate mofetil (104 children) for 30 months. The median age of the study participants was 8.2 years, and nearly half (46%) had congenital heart disease.
The primary efficacy measure was a composite score assessing acute cellular rejection, CAV, and CKD—collectively termed the MATE-3 score. For safety, researchers used a broader measure (MATE-6) that included additional factors such as antibody-mediated rejection, infection, and post-transplant lymphoproliferative disorder.
The study led to the following findings:
- At 30 months, there was no significant difference between the two treatment groups in the composite MATE-3 score, suggesting both regimens were equally effective in preventing major transplant-related complications.
- The mean difference between the groups was −0.32, indicating statistical non-significance.
- Safety outcomes were favorable, with no higher rate of overall transplant-related events in the everolimus group, meeting the noninferiority criteria for safety.
- Everolimus was linked to improved kidney function at 12 months, showing a mean increase in estimated glomerular filtration rate (eGFR) of 10.5 mL/min/1.73 m² compared with the standard regimen.
- The incidence of cytomegalovirus (CMV) infection was approximately 50% lower among participants receiving everolimus (hazard ratio, 0.50).
- Although everolimus did not offer superior results in patient or graft survival, MATE-free survival, or prevention of individual complications, it maintained a positive safety profile overall.
- Some children receiving everolimus experienced side effects such as aphthous stomatitis and hyperlipidemia, which were found to be manageable.
"Initiating everolimus with low-dose tacrolimus six months after pediatric heart transplant proved to be as effective as the standard tacrolimus-mycophenolate regimen in preventing rejection, CAV, and CKD. The therapy appeared safe, offered potential kidney benefits, and reduced CMV infection," the authors wrote.
"These findings provide valuable evidence to guide clinicians and regulators in optimizing long-term immunosuppressive strategies for pediatric heart transplant recipients," they concluded.
Reference:
Almond CS, Daly KP, Albers EL, et al. Everolimus and Low-Dose Tacrolimus After Heart Transplant in Children: A Randomized Clinical Trial. JAMA. 2025;334(15):1339–1348. doi:10.1001/jama.2025.14338
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