Tailoring of Immunosuppression With Belatacept in De Novo and Conversion Settings and Risk Mitigation Strategies

Although maintenance immunosuppression with calcineurin inhibitors (CNIs) has greatly reduced rejection rates in renal transplant recipients, long-term use can contribute to eventual nephrotoxicity, potentially leading to allograft injury and loss. Several clinical trials have shown that, compared with CNIs, belatacept-based maintenance immunosuppression can improve renal function, reduce the incidence of de novo donor-specific antibodies, and improve long-term patient/graft survival. However, the US Food and Drug Administration-approved belatacept-based regimen is also associated with higher acute rejection (AR) rates than CNI-based immunosuppression. Recent data from clinical trials and real-world studies suggest that initial posttransplant treatment with CNI-based immunosuppression followed by conversion to a belatacept-based regimen can lower the AR risk while preserving patient and renal health. This review article summarizes the available data pertaining to belatacept treatment protocols, with a focus on conversion to belatacept. Also discussed are studies of protocol modifications intended to further mitigate AR risks and belatacept-related outcomes in special populations, such as patients receiving marginal kidneys and those at risk of new-onset diabetes. Overall, the available data suggest that conversion from CNI- to belatacept-based immunosuppression ≥6 mo posttransplant appears to be effective in lowering the AR risk compared with belatacept use in the de novo setting or conversion <6 mo posttransplant. The addition of an extended transient or low-dose CNI treatment to de novo belatacept or a prolonged CNI taper in the conversion setting may also help lower the AR risk. However, additional studies will be needed to optimize the many variables applicable to belatacept treatment, particularly for different patient subgroups.