Meta-Analysis
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Mar 18, 2021; 11(3): 70-86
Published online Mar 18, 2021. doi: 10.5500/wjt.v11.i3.70
Belatacept in renal transplantation in comparison to tacrolimus and molecular understanding of resistance pattern: Meta-analysis and systematic review
Jayant Kumar, Isabella Reccia, Francesco Virdis, Mauro Podda, Ajay Kumar Sharma, Ahmed Halawa
Jayant Kumar, Isabella Reccia, Department of Cancer and Surgery, Imperial College, London W12 0HS, United Kingdom
Francesco Virdis, Department of Emergency General Surgery, Royal Free Hospital, London NW3 2QG, United Kingdom
Mauro Podda, Department of Surgery, General, Emergency and Robotic Surgical Unit, San Francesco Hospital, Nuoro 08100, Italy
Ajay Kumar Sharma, Department of Transplantation, Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom
Ahmed Halawa, Department of Surgery, Sheffield Teaching Hospitals, Sheffield S10 2JF, United Kingdom
Author contributions: Halawa A and Sharma AK designed the idea of study; Reccia I and Kumar J contributed to literature review and data collection; Kumar J, Reccia I, Podda M, Halawa A, and Sharma AK contributed to manuscript writing and critical revision.
Conflict-of-interest statement: None of the contributing authors have any conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jayant Kumar, MD, MSc, PhD, Academic Fellow, Attending Doctor, Senior Research Fellow, Department of Cancer and Surgery, Imperial College, DuCane, London W12 0HS, United Kingdom. jkumar@ic.ac.uk
Received: November 23, 2020
Peer-review started: November 23, 2020
First decision: December 21, 2020
Revised: December 23, 2020
Accepted: February 12, 2021
Article in press: February 12, 2021
Published online: March 18, 2021
ARTICLE HIGHLIGHTS
Research background

The T-cell costimulation blocking agent belatacept is considered as possible substitute for calcineurin inhibitors, however, no consensus has been established against its standard immunusuppressive drug Tacrolimus.

Research motivation

To find the alternative to current immunosuppressive medicine tacrolimus because of its high toxic adverse effects.

Research objectives

To understand the effectiveness of belatacept based maintenance immunosuppressive regimens in comparison to tacrolimus in renal transplantion through meta-analysis.

Research methods

The present meta-analysis was conducted following completion of registration (CRD42018086032) in Prospero an international database of prospectively registered systematic reviews. A detailed literature search was made on National Library of Medicine Database (PubMed), Embase, Cochrane, Crossref, Scopus databases, clinical trial registries on December 5, 2018 to determine the immunosuppressive role of belatacept as an alternative to Tac and analyis of data was performed through The Cochrane Collaboration, Review Manager (RevMan) Version 5.3.

Research results

The literature search revealed four prospective randomized control studies (n = 173 participants) comparing belatacept with tacrolimus. There was no significant difference in estimated renal function at 12 mo [mean difference 4.12 mL/min/1.73 m2, confidence interval (CI): -2.18 to 10.42, P = 0.20]. Further, belatacept group was associated with significant increase in biopsy proven acute rejection [relative risk (RR) = 3.27, CI: 0.88 to 12.11, P = 0.08] and worse 12 mo allograft survival (RR = 4.51, CI: 1.23 to 16.58, P = 0.02). Although, the incidence of new onset diabetes mellitus was lower with belatacept at 12 mo (RR = 0.26, CI: 0.07 to 0.99, P = 0.05).

Research conclusions

The meta-analysis demonstrated that belatacept-based maintenance immuno-suppression regimens were associated with an increased risk allograft loss in renal transplant recipients with equivalent renal functioning against standard tacrolimus. Further, the inclusion of belatacept as routine immunosuppresive agent in renal transplantation has been thwarted by increased rates of rejection and resistance owing to development of various effector memory T cells through, parallel differentiation and immunological plasticity.

Research perspectives

Study required to determine the safety and efficacy of belatacept in the setting of immunological sensitization and to better elucidate the mechanism of resistance and development of therapeutic strategies with focus on adhesion molecule blockade or abrogation of memory-specific responses.