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Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT ‐ EXT
Author(s) -
Bray R. A.,
Gebel H. M.,
Townsend R.,
Roberts M. E.,
Polinsky M.,
Yang L.,
MeierKriesche H.U.,
Larsen C. P.
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14738
Subject(s) - belatacept , immunosuppression , medicine , urology , immunology , transplantation , kidney transplantation , kidney transplant
BENEFIT and BENEFIT ‐ EXT were phase III studies of cytotoxic T‐cell crossmatch–negative kidney transplant recipients randomized to belatacept more intense ( MI )‐based, belatacept less intense ( LI )‐based, or cyclosporine‐based immunosuppression. Following study completion, presence/absence of HLA ‐specific antibodies was determined centrally via solid‐phase flow cytometry screening. Stored sera from anti‐ HLA –positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of donor‐specific antibodies ( DSA s), and mean fluorescent intensity ( MFI ) of any DSA s present. The effect of belatacept‐based and cyclosporine‐based immunosuppression on MFI was explored post hoc in patients with preexisting DSA s enrolled to BENEFIT and BENEFIT ‐ EXT . In BENEFIT , preexisting DSA s were detected in 4.6%, 4.9%, and 6.3% of belatacept MI ‐treated, belatacept LI ‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT ‐ EXT were 6.0%, 5.7%, and 9.2%. In both studies, most preexisting DSA s were of class I specificity. Over the first 24 months posttransplant, a greater proportion of preexisting DSA s in belatacept‐treated versus cyclosporine‐treated patients exhibited decreases or no change in MFI . MFI decline was more apparent with belatacept MI ‐based versus belatacept LI ‐based immunosuppression in both studies and more pronounced in BENEFIT ‐ EXT versus BENEFIT . Although derived post hoc, these data suggest that belatacept‐based immunosuppression decreases preexisting DSA s more effectively than cyclosporine‐based immunosuppression.