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Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review

The current gold standard to prevent allograft rejection for maintenance immunosuppression in kidney transplantation currently consists in glucocorticoids, an antiproliferative agent and a calcineurin inhibitor (CNI), with better outcome for tacrolimus than cyclosporin. Although, CNI drastically imp...

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Autores principales: Lombardi, Yannis, François, Hélène
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329606/
https://www.ncbi.nlm.nih.gov/pubmed/35911396
http://dx.doi.org/10.3389/fmed.2022.942665
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author Lombardi, Yannis
François, Hélène
author_facet Lombardi, Yannis
François, Hélène
author_sort Lombardi, Yannis
collection PubMed
description The current gold standard to prevent allograft rejection for maintenance immunosuppression in kidney transplantation currently consists in glucocorticoids, an antiproliferative agent and a calcineurin inhibitor (CNI), with better outcome for tacrolimus than cyclosporin. Although, CNI drastically improved early graft survival, so far, CNI have failed to significantly improve long-term survival mainly because of nephrotoxicity. In addition, CNI carry several other side effects such as an increased risk for cardiovascular events and for diabetes mellitus. Therefore, seeking alternatives to CNI remains of paramount importance in kidney transplantation. Belatacept is a fusion protein composed of the human IgG1 Fc fragment linked to the modified extracellular domain of cytotoxic T lymphocyte–associated antigen 4. In kidney transplant recipients, pivotal phase III randomized studies suggested clinical benefits of belatacept as an initial maintenance regimen, as compared with cyclosporine, mainly on kidney function. Recently, a randomized study also suggested a clinical benefit on renal function of a conversion from a CNI-based to a belatacept-based maintenance regimen in patients. However, conversion from CNIs to belatacept is probably associated with an increased risk of biopsy-proven acute rejection and should prompt close clinical surveillance. On the other hand, other studies suggest a decrease in de novo humoral transplant immunization. Belatacept is probably associated with an increase in both risk and severity of some infectious diseases, including EBV-linked post-transplantation lymphoproliferative disorders, and with a decreased response to vaccines. Most studies on belatacept are observational, retrospective, and non-comparative. Consequently, high-quality data about the safety and efficacy profile of belatacept, as compared with the current gold standard for maintenance regimens (tacrolimus-based), is uncertain. Our review will therefore focus on the most recent published data aiming at evaluating the evidence-based or the “true” benefits and risks of belatacept-based regimens in kidney transplantation.
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spelling pubmed-93296062022-07-29 Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review Lombardi, Yannis François, Hélène Front Med (Lausanne) Medicine The current gold standard to prevent allograft rejection for maintenance immunosuppression in kidney transplantation currently consists in glucocorticoids, an antiproliferative agent and a calcineurin inhibitor (CNI), with better outcome for tacrolimus than cyclosporin. Although, CNI drastically improved early graft survival, so far, CNI have failed to significantly improve long-term survival mainly because of nephrotoxicity. In addition, CNI carry several other side effects such as an increased risk for cardiovascular events and for diabetes mellitus. Therefore, seeking alternatives to CNI remains of paramount importance in kidney transplantation. Belatacept is a fusion protein composed of the human IgG1 Fc fragment linked to the modified extracellular domain of cytotoxic T lymphocyte–associated antigen 4. In kidney transplant recipients, pivotal phase III randomized studies suggested clinical benefits of belatacept as an initial maintenance regimen, as compared with cyclosporine, mainly on kidney function. Recently, a randomized study also suggested a clinical benefit on renal function of a conversion from a CNI-based to a belatacept-based maintenance regimen in patients. However, conversion from CNIs to belatacept is probably associated with an increased risk of biopsy-proven acute rejection and should prompt close clinical surveillance. On the other hand, other studies suggest a decrease in de novo humoral transplant immunization. Belatacept is probably associated with an increase in both risk and severity of some infectious diseases, including EBV-linked post-transplantation lymphoproliferative disorders, and with a decreased response to vaccines. Most studies on belatacept are observational, retrospective, and non-comparative. Consequently, high-quality data about the safety and efficacy profile of belatacept, as compared with the current gold standard for maintenance regimens (tacrolimus-based), is uncertain. Our review will therefore focus on the most recent published data aiming at evaluating the evidence-based or the “true” benefits and risks of belatacept-based regimens in kidney transplantation. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9329606/ /pubmed/35911396 http://dx.doi.org/10.3389/fmed.2022.942665 Text en Copyright © 2022 Lombardi and François. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Lombardi, Yannis
François, Hélène
Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review
title Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review
title_full Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review
title_fullStr Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review
title_full_unstemmed Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review
title_short Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review
title_sort belatacept in kidney transplantation: what are the true benefits? a systematic review
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329606/
https://www.ncbi.nlm.nih.gov/pubmed/35911396
http://dx.doi.org/10.3389/fmed.2022.942665
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