Comparative Effectiveness and Harms of Belatacept Versus Tacrolimus Among Kidney Transplant Recipients in The United States

Few studies have compared the effectiveness and harms of initiating belatacept versus tacrolimus for immunosuppression among kidney transplant recipients. We conducted a cohort study emulating a target trial using data from the United States Renal Data System and the Scientific Registry of Transplant Recipients. We included adult Medicare beneficiaries (≥18 years) undergoing first kidney transplantation in the U.S. from 2012-2020 who initiated belatacept or tacrolimus at transplant (intention-to-treat analysis). Effectiveness outcomes included a primary composite (death or graft failure), rejection at 1 year and 2 years, and kidney function assessed using estimated glomerular filtration rate (eGFR, mL/min/1.73 m²) at 6 months, 1 year and 2 years. Harm outcomes included post-transplantation diabetes mellitus, cardiac ischemic events (composite of acute myocardial infarction or revascularization procedures), post-transplantation lymphoproliferative disorders (PTLD), and mortality at 1 and 2 years. We standardized tacrolimus initiators to belatacept initiators using propensity score-derived weights. For all outcomes except mortality and eGFR, we estimated adjusted risk differences (aRD) and risk ratios (aRR) using weighted Aalen-Johansen estimators. For mortality, we used weighted Kaplan-Meier estimators to estimate aRD and aRR. For eGFR, we used generalized estimating equations to calculate weighted mean-differences.The cohort included 30,678 recipients, 870 initiating belatacept and 29,808 initiating tacrolimus. At 2 years, There was no evidence of between-group differences for the primary composite (12.15% versus 12.28%, aRD= -0.13%, 95% CI (-2.72%, 2.47%)). Compared with tacrolimus initiators, belatacept initiators had a higher risk of rejection (37.46% versus 24.54%, aRD= 12.91%, 95% CI (7.95%, 17.54%)). The weighted mean eGFR (ml/min/1.73m2) was 51.68 versus 50.01, differences=1.66; 95% CI (-0.94, 4.27)). Belatacept initiators had a lower incidence of post-transplantation diabetes mellitus (21.63% versus 26.80%, aRD= -5.17%, 95% CI (-9.81%, -0.43%) and a higher incidence of PTLD (3.73% versus 2.07%, aRD= 1.66%, 95% CI 0.21%, 3.03%). There were no differences in cardiac ischemic events (5.29% versus 5.38%, aRD= -0.10%, 95% CI -1.96%, 1.80%) or mortality (7.31% versus 6.83%, aRD= 0.47%, 95% CI-1.68%, 2.63%). Our findings provide real-world evidence on the comparative benefits and harms of belatacept versus tacrolimus initiation among kidney transplant recipients and may inform clinician-patient shared decision-making when selecting maintenance immunosuppression.