NEW IMMUNOSUPPRESSIVE AGENTS

J. Grinyo¹, B. Charpentier², J.O.M. Pestana³, H. De jonge⁴, F. Vincenti⁵, R. Shi⁶, M. Agarwal⁷, D. Thomas⁷, C. Larsen^8
1Nephrology Unit, Hospital Universitari de Bellvitge, Barcelona/SPAIN, ²Nephrology And Transplantation Dept, Bicetre Hospital, Paris/FRANCE, ³Nephrology, Hospital do Rim e Hipertensão, Sâo Paulo/BRAZIL, ⁴Nephrology Department, University Hospital Leuven, Leuven/BELGIUM, ⁵, UCSF, San Francisco/UNITED STATES OF AMERICA, ⁶, Bristol-Myers Squibb, Hopewell/NJ/UNITED STATES OF AMERICA, ⁷, Bristol-Myers Squibb, Princeton/NJ/UNITED STATES OF AMERICA, ⁸Emory Transplant Center, Emory University School of Medicine, Atlanta/GA/UNITED STATES OF AMERICA

Body: Introduction: Belatacept, a selective co-stimulation blocker, is associated with better renal function and an improved cardiovascular/metabolic risk profile vs cyclosporine (CsA) in kidney transplant recipients. The current analysis focuses on pooled safety data for belatacept vs CsA used in combination with basiliximab, MMF, and steroids through July 2009.
Methods: Patients in the 3 core studies were randomized to a more intensive (MI) or less intensive (LI) regimen of belatacept or CsA. The pooled analysis included 1425 intent-to-treat patients (MI = 477; LI = 472; CsA = 476). Median follow-up was ~2.4 yrs; some patients were followed for ~7 yrs.
Results: The incidence of death (MI: 6.5%; LI: 4.8%; CsA: 7.4%) was lower in the belatacept LI group, and the incidence of serious adverse events (MI: 71%; LI: 68%; CsA: 69%) was comparable between groups. The overall incidence of malignancies remained low, but was slightly higher in the MI group (MI: 10%; LI: 6%; CsA: 7%). 15 cases of PTLD occurred (n = 8 MI; n = 5 LI; n = 2 CsA) across the 3 studies, including 8 cases involving the CNS (n = 6 MI; n = 2 LI). EBV negative serostatus was the strongest risk factor; more PTLD cases occurred on the MI regimen. The frequency of serious infections was 37%, 32%, and 36% in the MI, LI, and CsA groups, respectively. Rates of polyoma (MI: 7%; LI: 3%; CsA: 6%) and fungal infections (MI: 22%; LI: 17%; CsA: 21%) were lower in the LI group vs the MI or CsA groups. 1 case of progressive multifocal leukoencephalopathy was reported in the MI group. Rates of herpes infections were higher in the belatacept groups (MI: 15%; LI: 13%; CsA: 10%). Tuberculosis occurred in 10 patients (n = 5 MI; n = 4 LI; n = 1 CsA); mostly in endemic areas. There were no reports of anaphylaxis or hypersensitivity to belatacept.
Conclusions: Longer-term treatment with belatacept-based regimens was generally safe. PTLD in the CNS was higher in belatacept vs CsA, especially in EBV- patients and with the MI dose. The incidence of deaths and serious infections was lower in the belatacept LI regimen. The overall balance of safety favored the LI regimen over the MI regimen.

Disclosure: All authors have declared no conflicts of interest.