Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy

Karen L Hardinger, Daniel Sunderland, Jennifer A Wiederrich Division of Pharmacy Practice and Administration, School of Pharmacy, University of Missouri–Kansas City, Kansas City, MO, USA Background: Belatacept is a novel immunosuppressive therapy designed to improve clinical outcomes associated with kidney transplant recipients while minimizing use of calcineurin inhibitors (CNIs). Methods: We searched for clinical trials related to administration of belatacept to kidney transplant patients compared to various immunosuppression regimens, as well as for studies that utilized data from belatacept trials to validate new surrogate measures. The purpose of this review is to consolidate the published evidence of belatacept’s effectiveness and safety in renal transplant recipients to better elucidate its place in clinical practice. Results: Analysis of the results from the Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppressive Trial (BENEFIT) study, a de novo trial that compared cyclosporine (CsA)-based therapy to belatacept-based therapy in standard criteria donors, found a significant difference in mean estimated glomerular filtration rate (eGFR) of 13–15 mL/min/1.73 m2 and 23–27 mL/min/1.73 m2 at 1 year and 7 years, respectively. The BENEFIT-EXT study was similarly designed with the exception that it included extended criteria donors. Renal function improved significantly for the more intensive belatacept group in all years of the BENEFIT-EXT study; however, it was not significant in the less intensive group until 5 years after transplant. Belatacept regimens resulted in lower blood pressure, cholesterol levels, and incidence of new-onset diabetes after transplant compared to CsA-based regimens. Results from conversion of CNIs to belatacept therapy, dual therapy of belatacept with sirolimus, and belatacept with corticosteroid avoidance therapy are also included in this article. Conclusion: The evidence reviewed in this article suggests that belatacept is an effective alternative in kidney transplant recipients. Compared to CNI-based therapy, belatacept-based therapy results in superior renal function and similar rates of allograft survival. In terms of safety, belatacept was shown to have lower incidence of hypertension, hyperlipidemia, and diabetes; however, incidence of posttransplantation lymphoproliferative disorder and the cost of belatacept may hinder use of this medication. Keywords: costimulatory blocker, renal, BENEFIT, pharmacology, immunosuppressio