Should Belatacept Be the Centrepiece of Renal Transplantation?

Monika Huber; Stephan Kemmner; Lutz Renders; Uwe Heemann

Disclosures

Nephrol Dial Transplant. 2016;31(12):1995-2002. 

In This Article

Abstract and Introduction

Abstract

Belatacept was developed to minimize cardiovascular risk and nephrotoxicity associated with calcineurin inhibitor (CNI)–based immunosuppression. Recently, 7-year data from the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT), a phase III study comparing belatacept with cyclosporine, have been published. While during the first year of belatacept the risk of acute rejection episodes was elevated, this seemingly had marginal consequences for long-term graft survival and function as well as patient survival.

For patients at a low-immunological risk, this drug seems to be a safe and effective alternative to CNI-based immunosuppression. Whether the higher rates of acute rejection episodes in the first year outweigh the gain in long-term graft function is still debated. In particular, the lower incidence of donor-specific antibodies indicates that belatacept should not be considered as lower intensity immunosuppression over the long term.

Therefore, should belatacept be the centrepiece of immunosuppression for renal patients?

All randomized trials so far have focussed on patients at a low immunological risk. Furthermore, cyclosporine A (CsA), the comparator of belatacept in BENEFIT and the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT), is not the CNI of choice in modern transplantation. Furthermore, while at Year 7 the rate of cancer and infections was comparable with the CsA group, long-term data are missing on safety issues for a large number of patients. Thus, currently belatacept may be the drug of choice for a select group of patients, but not for everyone.

This review highlights the benefits and uncertainties of the use of belatacept in kidney transplantation.

Introduction

The leading cause of mortality after renal transplantation is cardiovascular disease and may partly be due to increased cardiovascular risk factors such as hypertension, dyslipidaemia and glucose intolerance, or new onset of diabetes after transplantation (NODAT) as side effects of calcineurin inhibitors (CNIs), glucocorticoids and/or mammalian target of rapamycin (mTOR) inhibitors.[1–3]

An interesting new therapeutic concept as part of immunosuppressive therapy after renal transplantation is the selective co-stimulation blockade of T cell activation with the fusion protein belatacept.[4] Recently, a number of publications suggested markedly improved long-term patient and graft outcomes in patients treated with belatacept. Thus, we asked the question whether belatacept should be the centre piece of immunosuppression in renal transplantation. The purpose of this review is to outline the published evidence regarding the effectiveness and possible advantages, but also the safety aspects and limitations, of selective co-stimulation blockade with belatacept.

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