Combined Tacrolimus, Belatacept Regimen Improves Post-Kidney Transplant Outcomes

New research is shedding light on the potential benefits of combined belatacept and tacrolimus immunosuppression for kidney transplant recipients, with study findings suggesting this regimen is associated with better patient and all-cause graft survival compared with tacrolimus alone.1

Leveraging patient data from the United Network for Organ Sharing (UNOS) Kidney Standard Transplant Analysis and Research (STAR) file, the study found no overall difference between belatacept and tacrolimus-based regimens for patient survival, all-cause graft failure, or death-censored graft failure (DCGF). However, a combination of belatacept and low-dose tacrolimus following transplantation appeared to significantly improve outcomes versus tacrolimus alone.1

According to data from the Organ Procurement and Transplantation Network, in 2023, more than 27,000 kidney transplants were performed in the US. While calcineurin inhibitors have long been a mainstay of immunosuppression following transplantation, uncertainties exist about their impact on long-term outcomes.1,2

“Despite short-term graft survival improvement with calcineurin inhibitors, the long-term graft outcomes have been limited. Calcineurin inhibitors are associated with increased nephrotoxicity, hypertension, and post-transplant diabetes,” Bhavna Chopra, MD, a transplant nephrologist at Beth Israel Deaconess Medical Center, and colleagues wrote.1 “These nephrotoxic and metabolic side effects have been thought to limit long-term graft and patient outcomes. Hence, there has been an ongoing quest to find alternative regimens."

To compare the long-term outcomes of kidney transplant recipients on belatacept versus tacrolimus immunosuppression, investigators examined data from the UNOS STAR file for first living or deceased kidney-only transplants performed in adult patients ≥ 18 years of age from January 2010 to December 2022. Those who received depleting or non-depleting induction agents and were discharged on either tacrolimus or belatacept-based maintenance immunosuppression were included in the analysis.1

The study’s primary outcomes were all-cause allograft failure; DCGF; and overall patient death between patients discharged on tacrolimus or belatacept maintenance regimens using propensity score matching. Secondary outcomes included risk of delayed graft function, defined as dialysis within the first week of transplant; acute rejection rates within the first year post-transplant; and graft function measured by serum creatinine at 6 months and 1 year.1

Investigators identified 179,728 patients during the study period who were first-time kidney transplant recipients, received induction therapy, and were discharged on tacrolimus or belatacept-based immunosuppression from their index transplant admission. Among these patients, 2652 were discharged on belatacept, 174,863 were discharged on tacrolimus, and 2213 were discharged on both belatacept and tacrolimus.1

The final 1:5 propensity-matched cohorts included 2612 patients on belatacept versus 12,760 patients on tacrolimus and 2033 patients on belatacept and tacrolimus versus 9004 on tacrolimus alone.1

Upon analysis, there was no statistical difference between tacrolimus and belatacept groups in overall patient death (hazard ratio [HR], 1.03; 95% CI, 0.92-1.14); all-cause graft failure (HR, 1.07; 95% CI, 0.97-1.17); or DCGF (HR, 1.11; 95% CI, 0.98-1.25) (all P >.05).1

However, further sensitivity analysis on long-term outcomes of the second 1:5 propensity-matched cohort comparing patients on belatacept and tacrolimus versus tacrolimus alone demonstrated significantly reduced risks of death (HR, 0.87; 95% CI, 0.76–1.00; P = .043) and graft failure (HR, 0.73; 95% CI, 0.64–0.83; P <.001) with the combined regimen. Additional Subgroup analysis revealed belatacept and tacrolimus therapy was associated with decreased graft failure in recipients of deceased donor organs after brain death (HR, 0.72; 95% CI, 0.61–0.85; P <.001) and in recipients ≥ 65 years of age (HR, 0.70; 95% CI, 0.55–0.89; P = .004).1

Investigators noted transplant recipients who received non-depleting induction agents had a protective benefit of belatacept and tacrolimus when compared to tacrolimus alone in terms of death (HR, 0.81; 95% CI, 0.7, 0.95; P = .007); graft failure (HR, 0.64; 95% CI, 0.55, 0.74; P <.001); and DCGF (HR, 0.8; 95% CI, 0.67, 0.97; P = .023), whereas among those who received depleting agents, combined belatacept and tacrolimus was associated with an increased risk of graft loss (HR, 1.31; 95% CI, 1.02, 1.69; P = .036).1

“These findings suggest that belatacept with low-dose tacrolimus may have the added benefit of reducing the nephrotoxic effects by CNI minimization and reducing the rejection rates, which leads to better graft function and longer graft survival,” investigators concluded.1 “Large prospective randomized controlled studies are needed to clarify the long-term efficacy and safety of belatacept with or without tacrolimus across diverse patient populations.”

References

1. Canizares S, Montalvan A, Eckhoff D, et al. Long Term Outcomes of Transplant Recipients Comparing Belatacept vs. Tacrolimus: A UNOS Database Analysis. Clinical Transplantation. https://doi.org/10.1111/ctr.70075
2. Health Resources and Services Administration. Organ Donation Statistics. October 2024. Accessed January 29, 2025. https://www.organdonor.gov/learn/organ-donation-statistics