Optimization of de novo belatacept-based immunosuppression administered to renal transplant recipients

• Type of Material: Article
• Authors: Allan Kirk, Emory University; Andrew Adams, Emory University; Antoine Durrbach, Université Paris‐Saclay; Mandy Ford, Emory University; David A Hildeman, University of Cincinnati; Christian Larsen, Emory University; Flavio Vincenti, University of California San Francisco; David Wojciechowski, UT Southwestern; Steve E Woodle, University of Cincinnati
• Language: English
• Date: 2020-11-24
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/ajt.16386
• Title of Journal or Parent Work: AMERICAN JOURNAL OF TRANSPLANTATION
• Volume: 21
• Issue: 5
• Start Page: 1691
• End Page: 1698
• Keywords: TACROLIMUS; CYCLOSPORINE; NEUROTOXICITY; Life Sciences & Biomedicine; immunosuppression / immune modulation; T-CELLS; fusion proteins and monoclonal antibodies; kidney transplantation: living donor; rejection: acute; off-label drug use; MYCOPHENOLATE; maintenance; CALCINEURIN INHIBITOR; kidney transplantation / nephrology; clinical research / practice; RANDOMIZED-TRIAL; immunosuppressant; immunosuppressive regimens; Science & Technology; ALLOGRAFT-REJECTION; Transplantation; Surgery; KIDNEY-TRANSPLANTATION; PHASE-III; editorial / personal viewpoint
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Kidney transplant recipients administered belatacept-based maintenance immunosuppression present with a more favorable metabolic profile, reduced incidence of de novo donor-specific antibodies (DSAs), and improved renal function and long-term patient/graft survival relative to individuals receiving calcineurin inhibitor (CNI)-based immunosuppression. However, the rates and severity of acute rejection (AR) are greater with the approved belatacept-based regimen than with CNI-based immunosuppression. Although these early co-stimulation blockade-resistant rejections are typically steroid sensitive, the higher rate of cellular AR has led many transplant centers to adopt immunosuppressive regimens that differ from the approved label. This article summarizes the available data on these alternative de novo belatacept-based maintenance regimens. Steroid-sparing, belatacept-based immunosuppression (following T cell–depleting induction therapy) has been shown to yield AR rates comparable to those seen with CNI-based regimens. Concomitant treatment with belatacept plus a mammalian target of rapamycin inhibitor (mTORi; sirolimus or everolimus) has yielded AR rates ranging from 0 to 4%. Because the optimal induction agent and number of induction doses; blood levels of mTORi; and dose, duration, and use of corticosteroids have yet to be determined, larger prospective clinical trials are needed to establish the optimal alternative belatacept-based regimen for minimizing early cellular AR occurrence.