A Randomized Controlled Clinical Trial Comparing Belatacept With Tacrolimus After De Novo Kidney Transplantation.

Background: Belatacept, an inhibitor of the CD28-CD80/86 co-stimulatory pathway, allows for calcineurin-inhibitor free immunosuppressive therapy in kidney transplantation but is associated with a higher acute rejection risk than ciclosporin. Thus, no biomarker for belatacept-resistant rejection has been validated. In this randomized controlled trial, acute rejection-rate was compared between belatacept- and tacrolimus-treated patients and immunological biomarkers for acute rejection were investigated. Methods: Forty kidney-transplant recipients were 1:1 randomized to belatacept or tacrolimus combined with basiliximab, mycophenolate mofetil and prednisolone. The 1-year incidence of biopsy-proven acute rejection was monitored. Potential biomarkers, namely CD8+CD28-, CD4+CD57+PD1- and CD8+CD28++ EMRA T cells were measured pre and posttransplantation and correlated to rejection. Pharmacodynamic monitoring of belatacept was performed by measuring free CD86 on monocytes. Results: The rejection incidence was higher in belatacept-treated than tacrolimus-treated patients: 55% vs. 10%; p = 0.006. All 3 graft losses, due to rejection, occurred in the belatacept group. Although 4 of 5 belatacept-treated patients with >35 cells CD8+CD28++ EMRA T cells/[mu]L rejected, median pretransplant values of the biomarkers did not differ between belatacept-treated rejectors and nonrejectors. In univariable Cox regressions, the studied cell subsets were not associated with rejection-risk. CD86 molecules on circulating monocytes in belatacept-treated patients were saturated at all time points. Conclusions: Belatacept-based immunosuppressive therapy resulted in higher and more severe acute rejection compared to tacrolimus-based therapy. This trial did not identify cellular biomarkers predictive of rejection. In addition, the CD28-CD80/86 co-stimulatory pathway appeared to be sufficiently blocked by belatacept and did not predict rejection. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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