The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant

<b>Background</b>: Chronic antibody-mediated rejection (cAMR) constitutes a serious challenge in the long-term success of organ transplantation. It is associated with donor-specific antibodies (DSAs) which activate a complement pathway in response to the presence of human leukocyte antig...

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Main Authors: Łukasz Świątek, Miłosz Miedziaszczyk, Dominik Lewandowski, Filip Robakowski, Piotr Tyburski, Marta Jakubowska, Marek Karczewski, Ilona Idasiak-Piechocka
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Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/78
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author Łukasz Świątek
Miłosz Miedziaszczyk
Dominik Lewandowski
Filip Robakowski
Piotr Tyburski
Marta Jakubowska
Marek Karczewski
Ilona Idasiak-Piechocka
author_facet Łukasz Świątek
Miłosz Miedziaszczyk
Dominik Lewandowski
Filip Robakowski
Piotr Tyburski
Marta Jakubowska
Marek Karczewski
Ilona Idasiak-Piechocka
author_sort Łukasz Świątek
collection DOAJ
description <b>Background</b>: Chronic antibody-mediated rejection (cAMR) constitutes a serious challenge in the long-term success of organ transplantation. It is associated with donor-specific antibodies (DSAs) which activate a complement pathway in response to the presence of human leukocyte antigens (HLAs) on the graft, which results in chronic inflammation and leads to graft dysfunction. One of the recent promising methods of cAMR treatment is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody referred to as Tocilizumab (TCZ). The aim of the presented systematic review is to explore the existing knowledge regarding the effect of tocilizumab treatment on cAMR and to perform a meta-analysis of the available data. <b>Methods</b>: A systematic review was performed using the PRISMA 2020 Checklist and Flow diagram. A systematic review protocol was registered in PROSPERO: CRD42024510996. The bias assessment was obtained with Methodical Index for Non-Randomized Studies (MINORS), whereas meta-analysis was performed using MedCalc. <b>Results</b>: Five clinical trials with a total number of 105 patients were included in our review. The mean loss of eGFR in time was −0.141 mL/min/1.73 m<sup>2</sup> (95% CI: −0.409 to 0.126; <i>p</i> = 0.298) and was found to be statistically insignificant. The heterogeneity was low and was equal to I<sup>2</sup> = 0.00%. The authors demonstrated a reduction in DSA titer by TCZ (−0.266 MFI (95% CI: −0.861 to 0.329; <i>p</i> = 0.377)). In the majority of studies, eGFR stabilization was associated with a reduction in DSAs. <b>Conclusions</b>: TCZ pharmacotherapy insignificantly reduced DSA titer and eGFR. Despite promising outcomes of potential eGFR stabilization, there is a need for large randomized controlled trials comparing standard management of cAMR and tocilizumab treatment.
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spelling doaj-art-e3be2da3db754c4c8911cb8205cf23fe2025-01-24T13:45:51ZengMDPI AGPharmaceutics1999-49232025-01-011717810.3390/pharmaceutics17010078The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney TransplantŁukasz Świątek0Miłosz Miedziaszczyk1Dominik Lewandowski2Filip Robakowski3Piotr Tyburski4Marta Jakubowska5Marek Karczewski6Ilona Idasiak-Piechocka7Students Research Group of Transplantation and Kidney Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandDepartment of General and Transplant Surgery, Poznan University of Medical Sciences, 60-355 Poznan, PolandStudents Research Group of Transplantation and Kidney Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandStudents Research Group of Transplantation and Kidney Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandStudents Research Group of Transplantation and Kidney Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandStudents Research Group of Transplantation and Kidney Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandDepartment of General and Transplant Surgery, Poznan University of Medical Sciences, 60-355 Poznan, PolandDepartment of General and Transplant Surgery, Poznan University of Medical Sciences, 60-355 Poznan, Poland<b>Background</b>: Chronic antibody-mediated rejection (cAMR) constitutes a serious challenge in the long-term success of organ transplantation. It is associated with donor-specific antibodies (DSAs) which activate a complement pathway in response to the presence of human leukocyte antigens (HLAs) on the graft, which results in chronic inflammation and leads to graft dysfunction. One of the recent promising methods of cAMR treatment is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody referred to as Tocilizumab (TCZ). The aim of the presented systematic review is to explore the existing knowledge regarding the effect of tocilizumab treatment on cAMR and to perform a meta-analysis of the available data. <b>Methods</b>: A systematic review was performed using the PRISMA 2020 Checklist and Flow diagram. A systematic review protocol was registered in PROSPERO: CRD42024510996. The bias assessment was obtained with Methodical Index for Non-Randomized Studies (MINORS), whereas meta-analysis was performed using MedCalc. <b>Results</b>: Five clinical trials with a total number of 105 patients were included in our review. The mean loss of eGFR in time was −0.141 mL/min/1.73 m<sup>2</sup> (95% CI: −0.409 to 0.126; <i>p</i> = 0.298) and was found to be statistically insignificant. The heterogeneity was low and was equal to I<sup>2</sup> = 0.00%. The authors demonstrated a reduction in DSA titer by TCZ (−0.266 MFI (95% CI: −0.861 to 0.329; <i>p</i> = 0.377)). In the majority of studies, eGFR stabilization was associated with a reduction in DSAs. <b>Conclusions</b>: TCZ pharmacotherapy insignificantly reduced DSA titer and eGFR. Despite promising outcomes of potential eGFR stabilization, there is a need for large randomized controlled trials comparing standard management of cAMR and tocilizumab treatment.https://www.mdpi.com/1999-4923/17/1/78cAMRDSAeGFRkidney rejectiontocilizumab
spellingShingle Łukasz Świątek
Miłosz Miedziaszczyk
Dominik Lewandowski
Filip Robakowski
Piotr Tyburski
Marta Jakubowska
Marek Karczewski
Ilona Idasiak-Piechocka
The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant
Pharmaceutics
cAMR
DSA
eGFR
kidney rejection
tocilizumab
title The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant
title_full The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant
title_fullStr The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant
title_full_unstemmed The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant
title_short The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant
title_sort promising effect of tocilizumab on chronic antibody mediated rejection camr of kidney transplant
topic cAMR
DSA
eGFR
kidney rejection
tocilizumab
url https://www.mdpi.com/1999-4923/17/1/78
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