BMS1FY4018 Transplantation - July 1, 2011 - (Page 976)

CLINICAL AND TRANSLATIONAL RESEARCH Belatacept-Based Regimens Are Associated With Improved Cardiovascular and Metabolic Risk Factors Compared With Cyclosporine in Kidney Transplant Recipients (BENEFIT and BENEFIT-EXT Studies) Yves Vanrenterghem,1,13 Barbara Bresnahan,2 Josep Campistol,3 Antoine Durrbach,4 Josep Grinyo,5 ´ Hans-Hellmut Neumayer,6 Philippe Lang,7 Christian P. Larsen,8 Eduardo Mancilla-Urrea,9 Jose Medina Pestana,10 Alan Block,11 Tao Duan,11 Alan Glicklich,11 Sheila Gujrathi,11 and Flavio Vincenti12 ´ Background. Cardiovascular disease, the most common cause of death with a functioning graft among kidney transplant recipients, can be exacerbated by immunosuppressive drugs, particularly the calcineurin inhibitors. Belatacept, a selective co-stimulation blocker, may provide a better cardiovascular/metabolic risk profile than current immunosuppressants. Methods. Cardiovascular and metabolic endpoints from two Phase III studies (BENEFIT and BENEFIT-EXT) of belatacept-based regimens in kidney transplant recipients were assessed at month 12. Each study assessed belatacept in more intensive (MI) and less intensive (LI) regimens versus cyclosporine A (CsA). These secondary endpoints included changes in blood pressure, changes in serum lipids, and the incidence of new-onset diabetes after transplant (NODAT). Results. A total of 1209 patients were randomized and transplanted across the two studies. Mean systolic blood pressure was 6 to 9 mm Hg lower and mean diastolic blood pressure was 3 to 4 mm Hg lower in the MI and LI groups versus CsA (P 0.002) across both studies at month 12. Non-HDL cholesterol was lower in the belatacept groups versus CsA (P 0.01 MI or LI vs. CsA in each study). Serum triglycerides were lower in the belatacept groups versus CsA (P 0.02 MI or LI vs. CsA in each study). NODAT occurred less often in the belatacept groups versus CsA in a prespecified pooled analysis (P 0.05 MI or LI vs. CsA). Conclusions. At month 12, belatacept regimens were associated with better cardiovascular and metabolic risk profiles, with lower blood pressure and serum lipids and less NODAT versus CsA. The overall profile of belatacept will continue to be assessed over the 3-year trials. Keywords: Belatacept, Cyclosporine A, Cholesterol, Cardiovascular, Hypertension. (Transplantation 2011;91: 976–983) ardiovascular disease remains the most common cause of mortality in kidney transplant recipients with a functioning graft after transplantation (1, 2). Kidney transplant C recipients have an increased risk for atherosclerosis and ischemic heart disease (3– 6) and have up to a 50-fold increased annual risk of death related to cardiovascular disease comEmory University Transplant Center, Atlanta, GA. Instituto Nacional de Cardiologia “Dr Ignacio Chavez,” Mexico City, Mexico. 10 Division of Nephrology, Hospital do Rim e Hipertensao Unifesp, Sao ˜ Paulo, Brazil. 11 Bristol-Myers Squibb, Princeton, NJ. 12 Division of Nephrology, Department of Medicine, University of California, San Francisco, Kidney Transplant Service, San Francisco, CA. 13 Address correspondence to: Yves Vanrenterghem, M.D., Ph.D., Nephrology Department, University Hospital Leuven, UZ Gasthuisberg Herestraat 49, B3000 Leuven, Belgium. E-mail: yves.vanrenterghem@uz.kuleuven.ac.be Drs. Vanrenterghem, Grinyo, Larsen, Block, and Vincenti contributed to the research design; each author participated in the performance of the research and in data analysis; and Drs. Vanrenterghem, Vincenti, and Block participated in the writing of the manuscript, with input from the other authors. Received 16 November 2010. Accepted 16 December 2010. Copyright © 2011 by Lippincott Williams & Wilkins ISSN 0041-1337/11/9109-976 DOI: 10.1097/TP.0b013e31820c10eb 9 8 This work was supported by Bristol-Myers Squibb. Prof. Vanrenterghem has served as an advisor to Astellas Pharma, US. Prof. Campistol has participated in speakers bureaus for Wyeth and Novartis. Drs. Bresnahan, Durrbach, Neumayer, Lang, Mancilla-Urrea, and Medina Pestana have nothing to disclose. Prof. Grinyo has served as an advisor to Bristol-Myers Squibb. Dr. Larsen has received research grants/ contracts from Bristol-Myers Squibb and Genentech. Drs. Block, Duan, Glicklich, and Gujrathi are employees of Bristol-Myers Squibb. Dr. Vincenti has received research grants/contracts from Bristol-Myers Squibb, Pfizer, Novartis, Astellas Pharma, Genzyme, Genentech, and Roche. 1 Nephrology Department, University Hospital Leuven, Leuven, Belgium. 2 Division of Nephrology, Medical College of Wisconsin, Milwaukee, WI. 3 Department of Nephrology, Renal Transplantation Unit, Hospital Clinic i Provincial, University of Barcelona, Barcelona, Spain. 4 Service de Néphrologie et Transplantation, Bicetre Hospital, Kremlin ˆ Bicetre, IFRNT, Universite Paris sud, France. ˆ ´ 5 Department of Nephrology, University Hospital of Bellvitge, Barcelona, Spain. 6 Department of Nephrology, Charite, Campus Mitte, Universitatsmedizin, ´ ¨ Berlin, Germany. 7 Service de Néphrologie, Hospital Henri Mondor, Creteil, France. ´ 976 | www.transplantjournal.com Transplantation • Volume 91, Number 9, May 15, 2011 http://www.transplantjournal.com

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