Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial.

Immunosuppressive therapy in kidney transplantation is associated with numerous toxicities. CD28-mediated T cell costimulation blockade using belatacept may reduce long-term nephrotoxicity, compared with calcineurin inhibitor-based immunosuppression. The efficacy and safety of simultaneous calcineurin inhibitor avoidance and rapid steroid withdrawal were tested in a randomized, prospective, multi-center study. Methods All kidney transplants were performed using rapid steroid withdrawal immunosuppression. Recipients were randomized to 1:1:1 to receive belatacept with alemtuzumab induction, belatacept with rabbit antithymocyte globulin (rATG) induction, or tacrolimus with rATG induction. The composite endpoint consisted of death, kidney allograft loss, or an MDRD calculated eGFR of <45 ml/min/1.73m2 at 2 years. Results The composite endpoint was observed for 11/107 (10%) participants assigned to belatacept/alemtuzumab, 13/104 (13%) assigned to belatacept /rATG, and 21/105 (21%) assigned to tacrolimus/rATG (belatacept/alemtuzumab vs tacrolimus/rATG p = 0.99: belatacept/rATG vs tacrolimus/rATG p = 0.66). Patient and graft survival rates were similar between all groups. eGFR <45 ml/min/1.73m2 was observed for 9/107 (8%) participants assigned to belatacept/alemtuzuab, 8/104 (8%) participants assigned to belatacept/rATG, and 20/105 (19%) participants assigned to tacrolimus/rATG (p<0.05 for each belatacept group vs tacrolimus/rATG). Biopsy-proven acute rejection was observed for 20/107 (19%) participants assigned to belatacept/alemtuzuab, 26/104 (25%) participants assigned to belatacept/rATG, and 7/105 (7%) participants assigned to tacrolimus/rATG (belatacept/alemtuzumab vs tacrolimus/rATG p = 0.006: belatacept/rATG vs tacrolimus/rATG p < 0.001). Gastrointestinal and neurologic adverse events were less frequent with belatacept versus calcineurin based immunosuppression. Conclusions Overall two-year outcomes were similar comparing maintenance immunosuppression based on belatacept versus tacrolimus, each protocol with rapid steroid withdrawal. The incidence of eGFR <45 ml/min/1.73m2 was significantly lower but the incidence of biopsy proven acute rejection significantly higher with belatacept compared with tacrolimus.