An Integrated Safety Profile Analysis of Belatacept in Kidney Transplant Recipients

Date
2010-12-27Author
Grinyo, Josep
Charpentier, Bernard
Pestana, Jose Medina [UNIFESP]
Vanrenterghem, Yves
Vincenti, Flavio
Reyes-Acevedo, Rafael
Apanovitch, Anne Marie
Gujrathi, Sheila
Agarwal, Mamta
Thomas, Dolca
Larsen, Christian P.
Type
ArtigoISSN
0041-1337Is part of
TransplantationDOI
10.1097/TP.0b013e3182007b95Metadata
Show full item recordAbstract
Background. Belatacept is associated with better renal function and an improved cardiovascular/metabolic risk profile versus cyclosporine in kidney transplant recipients. the current analysis examined pooled safety data for belatacept versus cyclosporine used in combination with basiliximab, mycophenolate mofetil, and steroids.Methods. Patients enrolled in three core studies in de novo kidney transplantation were randomized to a more intensive (MI) or less intensive (LI) regimen of belatacept or cyclosporine. the pooled analysis included 1425 patients (MI: 477; LI: 472; cyclosporine: 476). Median follow-up was approximately 2.4 years.Results. Belatacept was generally well tolerated. the frequency of deaths (MI: 7%; LI: 5%; cyclosporine: 7%) and serious infections (MI: 37%; LI: 32%; cyclosporine: 36%) were lower in the LI group versus cyclosporine. the frequency of malignancies was 10%, 6%, and 7% in the MI, LI, and cyclosporine groups, respectively. Sixteen cases of posttransplant lymphoproliferative disorder (PTLD) occurred (n = 8 MI; n = 6 LI; n = 2 cyclosporine), including nine cases involving the central nervous system (CNS) (n = 6 MI; n = 3 LI). the risk of CNS PTLD was highest in Epstein-Barr virus(-) recipients; more CNS PTLD cases occurred in the MI group. One case of progressive multifocal leukoenceph-alopathy was reported in the MI group.Conclusions. Treatment with belatacept-based regimens was generally safe for a period of at least 2 years. There was a greater risk of PTLD-specifically CNS PTLD-in the belatacept groups versus cyclosporine, especially in Epstein-Barr virus(-) patients and with the MI dose. the number of deaths and serious infections was lower in the LI regimen versus MI and cyclosporine. the overall safety profile favored the LI over the MI regimen.
Citation
Transplantation. Philadelphia: Lippincott Williams & Wilkins, v. 90, n. 12, p. 1521-1527, 2010.Keywords
BelataceptCyclosporine
Kidney transplant
Safety
Posttransplant lymphoproliferative disorder
Sponsorship
Bristol-Myers SquibbPfizer
Novartis
Astellas Pharma
Genzyme
Genentech
Roche
International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
Collections
- EPM - Artigos [16302]