Three-year Outcomes in De Novo Liver Transplant Patients Receiving Everolimus With Reduced Tacrolimus: Follow-Up Results From a Randomized, Multicenter Study

被引:91
作者
Fischer, Lutz [1 ]
Saliba, Faouzi [2 ]
Kaiser, Gernot M. [3 ]
De Carlis, Luciano [4 ]
Metselaar, Herold J. [5 ]
De Simone, Paolo [6 ]
Duvoux, Christophe [7 ]
Nevens, Frederik [8 ]
Fung, John J. [9 ]
Dong, Gaohong [10 ]
Rauer, Barbara [11 ]
Junge, Guido [11 ]
机构
[1] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany
[2] Hop Paul Brousse, Villejuif, France
[3] Univ Duisburg Essen, Univ Hosp Essen, Essen, Germany
[4] Osped Niguarda Ca Granda, Milan, Italy
[5] Univ Rotterdam Hosp, Erasmus MC, Rotterdam, Netherlands
[6] Azienda Osped Univ Pisana, Pisa, Italy
[7] Hop Henri Mondor, F-94010 Creteil, France
[8] Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Leuven, Belgium
[9] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA
[10] Novartis Pharmaceut, E Hanover, NJ USA
[11] Novartis Pharma AG, Basel, Switzerland
关键词
RENAL-FUNCTION; CALCINEURIN-INHIBITORS; MYCOPHENOLATE-MOFETIL; CONTROLLED-TRIAL; DOSE TACROLIMUS; RECIPIENTS; DISEASE; RISK;
D O I
10.1097/TP.0000000000000555
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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(2) in the EVR+ Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m(2) 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.
引用
收藏
页码:1455 / 1462
页数:8
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