Three-year Outcomes in De Novo Liver Transplant Patients Receiving Everolimus With Reduced Tacrolimus: Follow-Up Results From a Randomized, Multicenter Study
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Three-year Outcomes in De Novo Liver Transplant Patients Receiving Everolimus With Reduced Tacrolimus: Follow-Up Results From a Randomized, Multicenter Study. / Fischer, Lutz; Saliba, Faouzi; Kaiser, Gernot M; De Carlis, Luciano; Metselaar, Herold J; De Simone, Paolo; Duvoux, Christophe; Nevens, Frederik; Fung, John J; Dong, Gaohong; Rauer, Barbara; Junge, Guido; H2304 Study Group.
In: TRANSPLANTATION, Vol. 99, No. 7, 07.2015, p. 1455-62.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Three-year Outcomes in De Novo Liver Transplant Patients Receiving Everolimus With Reduced Tacrolimus: Follow-Up Results From a Randomized, Multicenter Study
AU - Fischer, Lutz
AU - Saliba, Faouzi
AU - Kaiser, Gernot M
AU - De Carlis, Luciano
AU - Metselaar, Herold J
AU - De Simone, Paolo
AU - Duvoux, Christophe
AU - Nevens, Frederik
AU - Fung, John J
AU - Dong, Gaohong
AU - Rauer, Barbara
AU - Junge, Guido
AU - H2304 Study Group
PY - 2015/7
Y1 - 2015/7
N2 - BACKGROUND: Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration.METHODS: In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 to (i) everolimus + reduced exposure tacrolimus (EVR + Reduced TAC), (ii) everolimus + tacrolimus elimination (TAC Elimination), or (iii) standard exposure tacrolimus (TAC Control).RESULTS: Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR) during TAC withdrawal. Of 370 patients who completed the 24-month core study on-treatment, 282 (76.2%) entered an additional 12-month extension phase. The composite efficacy failure endpoint (tBPAR, graft loss or death) occurred in 11.5% of EVR+Reduced TAC patients versus 14.6% TAC Controls from randomization to month 36 (difference, -3.2%; 95% confidence interval, -10.5% to 4.2%; P = 0.334). Treated BPAR occurred in 4.8% versus 9.2% of patients (P = 0.076). From randomization to month 36, mean (SD) estimated glomerular filtration rate decreased by 7.0 (31.3) mL/min per 1.73 m in the EVR+Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m in the TAC Control group (P = 0.005). Rates of adverse events, serious adverse events, and discontinuation due to adverse events were similar in both groups during the extension.CONCLUSIONS: A clinically relevant renal benefit after introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study, with comparable efficacy and no late safety concerns.
AB - BACKGROUND: Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration.METHODS: In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 to (i) everolimus + reduced exposure tacrolimus (EVR + Reduced TAC), (ii) everolimus + tacrolimus elimination (TAC Elimination), or (iii) standard exposure tacrolimus (TAC Control).RESULTS: Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR) during TAC withdrawal. Of 370 patients who completed the 24-month core study on-treatment, 282 (76.2%) entered an additional 12-month extension phase. The composite efficacy failure endpoint (tBPAR, graft loss or death) occurred in 11.5% of EVR+Reduced TAC patients versus 14.6% TAC Controls from randomization to month 36 (difference, -3.2%; 95% confidence interval, -10.5% to 4.2%; P = 0.334). Treated BPAR occurred in 4.8% versus 9.2% of patients (P = 0.076). From randomization to month 36, mean (SD) estimated glomerular filtration rate decreased by 7.0 (31.3) mL/min per 1.73 m in the EVR+Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m in the TAC Control group (P = 0.005). Rates of adverse events, serious adverse events, and discontinuation due to adverse events were similar in both groups during the extension.CONCLUSIONS: A clinically relevant renal benefit after introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study, with comparable efficacy and no late safety concerns.
KW - Adult
KW - Aged
KW - Drug Administration Schedule
KW - Drug Therapy, Combination
KW - Europe
KW - Everolimus
KW - Female
KW - Glomerular Filtration Rate
KW - Graft Rejection
KW - Graft Survival
KW - Humans
KW - Immunosuppressive Agents
KW - Kidney
KW - Liver Transplantation
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - Risk Factors
KW - Tacrolimus
KW - Time Factors
KW - Treatment Outcome
KW - Journal Article
KW - Multicenter Study
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1097/TP.0000000000000555
DO - 10.1097/TP.0000000000000555
M3 - SCORING: Journal article
C2 - 26151607
VL - 99
SP - 1455
EP - 1462
JO - TRANSPLANTATION
JF - TRANSPLANTATION
SN - 0041-1337
IS - 7
ER -
