Flavio Vincenti1, Lionel Rostaing, Joseph Grinyo, Kim Rice, Steven Steinberg, Luis Gaite, Marie-Christine Moal, Guillermo A Mondragon-Ramirez, Jatin Kothari, Martin S Polinsky, Herwig-Ulf Meier-Kriesche, Stephane Munier, Christian P Larsen. 1. From the University of California, San Francisco, San Francisco (F.V.), and Sharp Memorial Hospital, San Diego (S.S.) - both in California; University Hospital and INSERM Unité 563, IFR-BMT, Toulouse (L.R.), and Hôpital de La Cavale Blanche, Brest (M.-C.M.) - both in France; University Hospital Bellvitge, Barcelona (J.G.); Baylor University Medical Center, Dallas (K.R.); Clínica de Nefrología, Santa Fe, Argentina (L.G.); Instituto Mexicano de Trasplantes, Morelos, Mexico (G.A.M.-R.); Hinduja Hospital, Hinduja Health Care and Apex Kidney Foundation, Mumbai, India (J.K.); Bristol-Myers Squibb, Princeton, NJ (M.S.P., H.-U.M.-K.); Bristol-Myers Squibb, Braine-l'Alleud, Belgium (S.M.); and Emory University Transplant Center, Atlanta (C.P.L.).
Abstract
BACKGROUND: In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. METHODS: We randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). RESULTS: A total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with thecyclosporine regimen were followed for the full 84-month period; all available data were used in the analysis. A 43% reduction in the risk of death or graft loss was observed for both the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine regimen (hazard ratio with the more-intensive regimen, 0.57; 95% confidence interval [CI], 0.35 to 0.95; P=0.02; hazard ratio with the less-intensive regimen, 0.57; 95% CI, 0.35 to 0.94; P=0.02), with equal contributions from the lower rates of death and graft loss. The mean estimated glomerular filtration rate (eGFR) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine regimen. The cumulative frequencies of serious adverse events at month 84 were similar across treatment groups. CONCLUSIONS: Seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less-intensive regimen) than with cyclosporine. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00256750.).
RCT Entities:
BACKGROUND: In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. METHODS: We randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). RESULTS: A total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all available data were used in the analysis. A 43% reduction in the risk of death or graft loss was observed for both the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine regimen (hazard ratio with the more-intensive regimen, 0.57; 95% confidence interval [CI], 0.35 to 0.95; P=0.02; hazard ratio with the less-intensive regimen, 0.57; 95% CI, 0.35 to 0.94; P=0.02), with equal contributions from the lower rates of death and graft loss. The mean estimated glomerular filtration rate (eGFR) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine regimen. The cumulative frequencies of serious adverse events at month 84 were similar across treatment groups. CONCLUSIONS: Seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less-intensive regimen) than with cyclosporine. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00256750.).
Authors: Roslyn B Mannon; Brian Armstrong; Peter G Stock; Aneesh K Mehta; Alton B Farris; Natasha Watson; Yvonne Morrison; Minnie Sarwal; Tara Sigdel; Nancy Bridges; Mark Robien; Kenneth A Newell; Christian P Larsen Journal: Am J Transplant Date: 2020-07-13 Impact factor: 8.086
Authors: Daniel E Weiner; Meyeon Park; Hocine Tighiouart; Alin A Joseph; Myra A Carpenter; Nitender Goyal; Andrew A House; Chi-Yuan Hsu; Joachim H Ix; Paul F Jacques; Clifton E Kew; S Joseph Kim; John W Kusek; Todd E Pesavento; Marc A Pfeffer; Stephen R Smith; Matthew R Weir; Andrew S Levey; Andrew G Bostom Journal: Am J Kidney Dis Date: 2018-07-20 Impact factor: 8.860
Authors: Jordana B Cohen; Kevin C Eddinger; Kimberly A Forde; Peter L Abt; Deirdre Sawinski Journal: Transplantation Date: 2017-10 Impact factor: 4.939