Long-term cost-effectiveness of belatacept vs. tacrolimus in kidney transplantation: Trade-off between metabolic benefit and immunological risk

Aims: This study aimed to evaluate the long-term cost-effectiveness of belatacept vs. tacrolimus as maintenance immunosuppression in adult kidney transplant recipients, focusing on the trade-off between reduced new-onset diabetes after transplantation (NODAT), immunological risk and potential renal benefit. Methods: A cohort Markov model with a 20-year horizon was developed from the Italian National Health Service perspective as the primary cost-effectiveness framework and complemented by individual-level Monte Carlo microsimulation to characterize variability in simulated clinical trajectories and outcome distributions. Five health states were modelled: functioning graft, functioning graft with NODAT, graft loss, retransplantation and death. Clinical inputs were drawn from comparative studies and a randomized trial. Outcomes were costs, life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefit (INMB). Deterministic and probabilistic sensitivity analyses and multiple scenarios assessed robustness. Results: Belatacept incurred higher lifetime costs than tacrolimus (€340 569 vs. €188 816; incremental €151 753) for gains (11.19 vs.11.10 QALYs), giving an ICER of €1 540 779/QALY and a negative INMB at €30 000/QALY. The most favourable scenario (renal benefit) reduced the ICER to €604 095/QALY; alternative rejection assumptions gave comparable results. Probabilistic analysis confirmed non–cost-effectiveness (aggregate ICER €1 596 119/QALY; ~0% probability of cost-effectiveness at €30 000–€50 000/QALY). Microsimulation showed lower NODAT incidence and longer functioning graft persistence with belatacept, with an incremental QALY advantage emerging mainly in the second decade. Conclusions: Belatacept offers metabolic advantages and modest quality-adjusted survival gains but is not cost-effective vs. tacrolimus owing to substantially higher costs. Whether longer lived or higher metabolic-risk recipients derive acceptable value is a hypothesis requiring dedicated age- and risk-stratified evaluation.