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Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT

BENEFIT and BENEFIT‐EXT were phase III studies of cytotoxic T‐cell crossmatch–negative kidney transplant recipients randomized to belatacept more intense (MI)‐based, belatacept less intense (LI)‐based, or cyclosporine‐based immunosuppression. Following study completion, presence/absence of HLA‐speci...

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Autores principales: Bray, R. A., Gebel, H. M., Townsend, R., Roberts, M. E., Polinsky, M., Yang, L., Meier‐Kriesche, H.‐U., Larsen, C. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055813/
https://www.ncbi.nlm.nih.gov/pubmed/29573335
http://dx.doi.org/10.1111/ajt.14738
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author Bray, R. A.
Gebel, H. M.
Townsend, R.
Roberts, M. E.
Polinsky, M.
Yang, L.
Meier‐Kriesche, H.‐U.
Larsen, C. P.
author_facet Bray, R. A.
Gebel, H. M.
Townsend, R.
Roberts, M. E.
Polinsky, M.
Yang, L.
Meier‐Kriesche, H.‐U.
Larsen, C. P.
author_sort Bray, R. A.
collection PubMed
description BENEFIT and BENEFIT‐EXT were phase III studies of cytotoxic T‐cell crossmatch–negative kidney transplant recipients randomized to belatacept more intense (MI)‐based, belatacept less intense (LI)‐based, or cyclosporine‐based immunosuppression. Following study completion, presence/absence of HLA‐specific antibodies was determined centrally via solid‐phase flow cytometry screening. Stored sera from anti‐HLA–positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of donor‐specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs present. The effect of belatacept‐based and cyclosporine‐based immunosuppression on MFI was explored post hoc in patients with preexisting DSAs enrolled to BENEFIT and BENEFIT‐EXT. In BENEFIT, preexisting DSAs were detected in 4.6%, 4.9%, and 6.3% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 6.0%, 5.7%, and 9.2%. In both studies, most preexisting DSAs were of class I specificity. Over the first 24 months posttransplant, a greater proportion of preexisting DSAs in belatacept‐treated versus cyclosporine‐treated patients exhibited decreases or no change in MFI. MFI decline was more apparent with belatacept MI‐based versus belatacept LI‐based immunosuppression in both studies and more pronounced in BENEFIT‐EXT versus BENEFIT. Although derived post hoc, these data suggest that belatacept‐based immunosuppression decreases preexisting DSAs more effectively than cyclosporine‐based immunosuppression.
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spelling pubmed-60558132018-07-30 Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT Bray, R. A. Gebel, H. M. Townsend, R. Roberts, M. E. Polinsky, M. Yang, L. Meier‐Kriesche, H.‐U. Larsen, C. P. Am J Transplant Brief Communications BENEFIT and BENEFIT‐EXT were phase III studies of cytotoxic T‐cell crossmatch–negative kidney transplant recipients randomized to belatacept more intense (MI)‐based, belatacept less intense (LI)‐based, or cyclosporine‐based immunosuppression. Following study completion, presence/absence of HLA‐specific antibodies was determined centrally via solid‐phase flow cytometry screening. Stored sera from anti‐HLA–positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of donor‐specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs present. The effect of belatacept‐based and cyclosporine‐based immunosuppression on MFI was explored post hoc in patients with preexisting DSAs enrolled to BENEFIT and BENEFIT‐EXT. In BENEFIT, preexisting DSAs were detected in 4.6%, 4.9%, and 6.3% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 6.0%, 5.7%, and 9.2%. In both studies, most preexisting DSAs were of class I specificity. Over the first 24 months posttransplant, a greater proportion of preexisting DSAs in belatacept‐treated versus cyclosporine‐treated patients exhibited decreases or no change in MFI. MFI decline was more apparent with belatacept MI‐based versus belatacept LI‐based immunosuppression in both studies and more pronounced in BENEFIT‐EXT versus BENEFIT. Although derived post hoc, these data suggest that belatacept‐based immunosuppression decreases preexisting DSAs more effectively than cyclosporine‐based immunosuppression. John Wiley and Sons Inc. 2018-04-17 2018-07 /pmc/articles/PMC6055813/ /pubmed/29573335 http://dx.doi.org/10.1111/ajt.14738 Text en © 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Brief Communications
Bray, R. A.
Gebel, H. M.
Townsend, R.
Roberts, M. E.
Polinsky, M.
Yang, L.
Meier‐Kriesche, H.‐U.
Larsen, C. P.
Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT
title Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT
title_full Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT
title_fullStr Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT
title_full_unstemmed Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT
title_short Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT
title_sort posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: post hoc analyses of benefit and benefit‐ext
topic Brief Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055813/
https://www.ncbi.nlm.nih.gov/pubmed/29573335
http://dx.doi.org/10.1111/ajt.14738
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