Three-Year Outcomes from BENEFIT, a Randomized, Active-Controlled, Parallel-Group Study in Adult Kidney Transplant Recipients

Vincenti, Flavio; Larsen, Christian; Alberú, Josefina; Bresnahan, Barbara A.; Garcı́a, Valter Duro; Kothari, Jatin; Lang, Philippe; Urrea, Eduardo Mancilla; Massari, P.; Mondragón-Ramírez, Guillermo; Reyes‐Acevedo, Rafael; Rice, K.; Rostaing, Lionel; Steinberg, Steven M.; Xing, Jun; Agarwal, Mamta; Harler, M. B.; Charpentier, B

doi:10.1111/j.1600-6143.2011.03785.x

Cited by 286 publications

(248 citation statements)

References 34 publications

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“…These findings are consistent with analyses performed at 3 years posttransplant,12, 13 which suggests that the effects of belatacept on preventing de novo DSA development are sustained over time. In the subset of patients in BENEFIT and BENEFIT‐EXT who developed de novo DSAs, belatacept‐based treatment appeared to result in lower antibody titers compared with cyclosporine‐based treatment.…”

Section: Discussionsupporting

confidence: 88%

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

Bray

Gebel

Townsend

et al. 2018

American Journal of Transplantation

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103

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Donor‐specific antibodies (DSAs) are associated with an increased risk of antibody‐mediated rejection and graft failure. In BENEFIT and BENEFIT‐EXT, kidney‐transplant recipients were randomized to receive belatacept more intense (MI)–based, belatacept less intense (LI)–based, or cyclosporine‐based immunosuppression for up to 7 years (84 months). The presence/absence of HLA‐specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid‐phase flow‐cytometry screening. Samples from anti‐HLA‐positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of DSAs, and mean fluorescence intensity (MFI) of any DSAs present. In BENEFIT, de novo DSAs developed in 1.4%, 3.5%, and 12.1% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 3.8%, 1.1%, and 11.2%. Per Kaplan‐Meier analysis, de novo DSA incidence was significantly lower in belatacept‐treated vs cyclosporine‐treated patients over 7 years in both studies (P < .01). In patients who developed de novo DSAs, belatacept‐based immunosuppression was associated with numerically lower MFI vs cyclosporine‐based immunosuppression. Although derived post hoc, these data suggest that belatacept‐based immunosuppression suppresses de novo DSA development more effectively than cyclosporine‐based immunosuppression.

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Section: Discussionsupporting

confidence: 88%

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

Bray

Gebel

Townsend

et al. 2018

American Journal of Transplantation

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103

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“…14 It is noteworthy to differentiate our results from the belatacept phase III trial, which showed higher rates of early endarteritis (18% versus 4%) and slightly less DSA (4% versus 7%) but superior renal function and comparable graft survival through 5 years in patients treated with belatacept versus cyclosporin, respectively. [24][25][26] Another study indicated that patients treated with belatacept had more T-regulatory cells in biopsies during rejection compared with patients treated with calcineurin inhibitor, 27 suggesting that belatacept may ease recovery from acute rejection by selective immune regulation. In contrast, most patients in our cohort were on calcineurin inhibitors, and endarteritis unresponsive to anti-T cell therapy was a poor prognostic indicator.…”

Section: Discussionmentioning

confidence: 99%

Isolated Endarteritis and Kidney Transplant Survival

Sis

Bagnasco²,

Cornell

et al. 2015

Journal of the American Society of Nephrology

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Isolated endarteritis of kidney transplants is increasingly recognized. Notably, microarray studies revealed absence of immunologic signatures of rejection in most isolated endarteritis biopsy samples. We investigated if isolated endarteritis responds to rejection treatment and affects kidney transplant survival. We retrospectively enrolled recipients of kidney transplant who underwent biopsies between 1999 and 2011 at seven American and Canadian centers. Exclusion criteria were recipients were blood group-incompatible or crossmatch-positive or had C4d-positive biopsy samples. After biopsy confirmation, patients were divided into three groups: isolated endarteritis (n=103), positive controls (type I acute T cell-mediated rejection with endarteritis; n=101), and negative controls (no diagnostic rejection; n=103). Primary end points were improved kidney function after rejection treatment and transplant failure. Mean decrease in serum creatinine from biopsy to 1 month after rejection treatment was 132.6 mmol/L (95% confidence interval [95% CI], 78.7 to 186.5) in patients with isolated endarteritis, 96.4 mmol/L (95% CI, 48.6 to 143.2) in positive controls (P=0.32), and 18.6 mmol/L (95% CI, 1.8 to 35.4) in untreated negative controls (P,0.001). Functional improvement after rejection treatment occurred in 80% of patients with isolated endarteritis and 81% of positive controls (P=0.72). Over the median 3.2-year followup period, kidney transplant survival rates were 79% in patients with isolated endarteritis, 79% in positive controls, and 91% in negative controls (P=0.01). In multivariate analysis, isolated endarteritis was associated with an adjusted 3.51-fold (95% CI, 1.16 to 10.67; P=0.03) risk for transplant failure. These data indicate that isolated endarteritis is an independent risk factor for kidney transplant failure.

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“…BENEFIT-extended criteria donor transplant recipients (BENEFIT-EXT) was similar to BENEFIT, except for the use of extended criteria donors. Despite higher rates of early acute rejection (AR) compared with patients treated with CsA, patients treated with belatacept had superior allograft function (higher calculated GFR [cGFR]) at 1 year that was sustained over 3 years, with equivalent patient and graft survival (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…Belatacept, which is now approved for use in adult renal transplant patients, has been compared with a CNI-based regimen using cyclosporine (CsA) in Phase 3 trials (6)(7)(8)(9). The Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial (BENEFIT) was a 3-year, multicenter, randomized, prospective study that included 666 adult kidney transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Profiling of Belatacept and Calcineurin Inhibitor Therapy in Renal Allograft Recipients

Vitalone

Ganguly

Hsieh

et al. 2014

American Journal of Transplantation

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Three-Year Outcomes from BENEFIT, a Randomized, Active-Controlled, Parallel-Group Study in Adult Kidney Transplant Recipients

Cited by 286 publications

References 34 publications

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

Isolated Endarteritis and Kidney Transplant Survival

Transcriptional Profiling of Belatacept and Calcineurin Inhibitor Therapy in Renal Allograft Recipients

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