Conversion from Calcineurin Inhibitor- to Belatacept-Based Maintenance Immunosuppression in Renal Transplant Recipients: A Randomized Phase 3b Trial

Abstract

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 evaluated the efficacy and 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 end point 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 rates of survival with graft function were 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 versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m 2 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 post-transplant 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.Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based, NCT01820572.