Conversion from Calcineurin Inhibitor to Belatacept-based Maintenance Immunosuppression in Renal Transplant Recipients: a Randomized Phase 3b Trial.

Background Calcineurin inhibitors (CNIs) are standard-of-care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T-cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial (NCT01820572) evaluated the efficacy/safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients. Methods Stable adult kidney transplant recipients, 6-60 months post-transplantation under CNI-based immunosuppression, were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary endpoint was the percentage of patients surviving with a functioning graft at 24 months. Results Overall, 446 renal transplant recipients were randomized to belatacept conversion (n=223) or CNI continuation (n=223). The 24-month rate of survival with graft function was 98% and 97% in the belatacept and CNI groups, respectively, (adjusted difference: 0.8 [95.1% CI, -2.1 to 3.7]). In the belatacept conversion vs. CNI continuation groups, respectively, 8% vs. 4% of patients experienced biopsy-proven acute rejection (BPAR) and 1% vs. 7% developed de novo donor-specific antibodies (dnDSA). The 24-month estimated glomerular filtration rate was higher with belatacept (55.5 vs. 48.5 mL/min1.73 m2 with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had posttransplant lymphoproliferative disorder. Conclusions Switching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate, but a lower incidence of dnDSA.