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.