title: An integrated safety profile analysis of belatacept in kidney transplant recipients.
abstract: 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 leukoencephalopathy 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.
authors.affiliation: Division of Nephrology, University Hospital of Bellvitge, Barcelona, Spain. jgrinyo@bellvitgehospital.cat
authors.forename: Josep
authors.initials: J
authors.lastname: Grinyó
authors.forename: Bernard
authors.initials: B
authors.lastname: Charpentier
authors.forename: José Medina
authors.initials: JM
authors.lastname: Pestana
authors.forename: Yves
authors.initials: Y
authors.lastname: Vanrenterghem
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
authors.forename: Rafael
authors.initials: R
authors.lastname: Reyes-Acevedo
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Apanovitch
authors.forename: Sheila
authors.initials: S
authors.lastname: Gujrathi
authors.forename: Mamta
authors.initials: M
authors.lastname: Agarwal
authors.forename: Dolca
authors.initials: D
authors.lastname: Thomas
authors.forename: Christian P
authors.initials: CP
authors.lastname: Larsen
mesh_terms: D000069594:Abatacept; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007239:Infections / Q000453:epidemiology / Q000401:mortality; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D011183:Postoperative Complications / Q000453:epidemiology / Q000401:mortality; D013997:Time Factors
chemical_list: D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept; D016572:Cyclosporine