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Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long-Term Renal Allograft Function.
Am J Transplant. 2017 Nov; 17(11):2922-2936.AJ

Abstract

Belatacept, a T cell costimulation blocker, demonstrated superior renal function, lower cardiovascular risk, and improved graft and patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011, we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n = 535) with a historical cohort receiving a tacrolimus-based protocol (n = 205). Patient and graft survival were equivalent for all groups. An increased rate of acute rejection was observed in an initial cohort treated with a protocol similar to the low-intensity regimen from the BENEFIT trial versus the historical tacrolimus group (50.5% vs. 20.5%). The addition of a transient course of tacrolimus reduced rejection rates to acceptable levels (16%). Treatment with belatacept was associated with superior estimated GFR (belatacept 63.8 mL/min vs. tacrolimus 46.2 mL/min at 4 years, p < 0.0001). There were no differences in serious infections including rates of cytomegalovirus or BK viremia. We describe the development of a costimulatory blockade-based strategy that ultimately allows renal transplant recipients to achieve calcineurin inhibitor-free immunosuppression.

Authors+Show Affiliations

Emory Transplant Center, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA.School of Public Health, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA. School of Public Health, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA. Renal Division, Department of Medicine, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA. Renal Division, Department of Medicine, Emory University, Atlanta, GA.Department of Surgery, Duke University, Durham, NC.Emory Transplant Center, Emory University, Atlanta, GA. Renal Division, Department of Medicine, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA.Emory Transplant Center, Emory University, Atlanta, GA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28544101

Citation

Adams, A B., et al. "Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long-Term Renal Allograft Function." American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol. 17, no. 11, 2017, pp. 2922-2936.
Adams AB, Goldstein J, Garrett C, et al. Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long-Term Renal Allograft Function. Am J Transplant. 2017;17(11):2922-2936.
Adams, A. B., Goldstein, J., Garrett, C., Zhang, R., Patzer, R. E., Newell, K. A., Turgeon, N. A., Chami, A. S., Guasch, A., Kirk, A. D., Pastan, S. O., Pearson, T. C., & Larsen, C. P. (2017). Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long-Term Renal Allograft Function. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 17(11), 2922-2936. https://doi.org/10.1111/ajt.14353
Adams AB, et al. Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long-Term Renal Allograft Function. Am J Transplant. 2017;17(11):2922-2936. PubMed PMID: 28544101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long-Term Renal Allograft Function. AU - Adams,A B, AU - Goldstein,J, AU - Garrett,C, AU - Zhang,R, AU - Patzer,R E, AU - Newell,K A, AU - Turgeon,N A, AU - Chami,A S, AU - Guasch,A, AU - Kirk,A D, AU - Pastan,S O, AU - Pearson,T C, AU - Larsen,C P, Y1 - 2017/07/03/ PY - 2016/05/23/received PY - 2017/04/13/revised PY - 2017/04/21/accepted PY - 2017/5/26/pubmed PY - 2018/6/28/medline PY - 2017/5/26/entrez KW - clinical research/practice KW - costimulation KW - fusion proteins and monoclonal antibodies: belatacept KW - fusion proteins and monoclonal antibodies: costimulation molecule specific KW - health services and outcomes research KW - immunosuppressant KW - immunosuppression/immune modulation KW - kidney (allograft) function/dysfunction KW - kidney transplantation/nephrology KW - rejection: T cell mediated (TCMR) SP - 2922 EP - 2936 JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JO - Am. J. Transplant. VL - 17 IS - 11 N2 - Belatacept, a T cell costimulation blocker, demonstrated superior renal function, lower cardiovascular risk, and improved graft and patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011, we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n = 535) with a historical cohort receiving a tacrolimus-based protocol (n = 205). Patient and graft survival were equivalent for all groups. An increased rate of acute rejection was observed in an initial cohort treated with a protocol similar to the low-intensity regimen from the BENEFIT trial versus the historical tacrolimus group (50.5% vs. 20.5%). The addition of a transient course of tacrolimus reduced rejection rates to acceptable levels (16%). Treatment with belatacept was associated with superior estimated GFR (belatacept 63.8 mL/min vs. tacrolimus 46.2 mL/min at 4 years, p < 0.0001). There were no differences in serious infections including rates of cytomegalovirus or BK viremia. We describe the development of a costimulatory blockade-based strategy that ultimately allows renal transplant recipients to achieve calcineurin inhibitor-free immunosuppression. SN - 1600-6143 UR - https://www.unboundmedicine.com/medline/citation/28544101/Belatacept_Combined_With_Transient_Calcineurin_Inhibitor_Therapy_Prevents_Rejection_and_Promotes_Improved_Long_Term_Renal_Allograft_Function_ L2 - https://doi.org/10.1111/ajt.14353 DB - PRIME DP - Unbound Medicine ER -