In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) þ Reduced tacrolimus (TAC; n ¼ 245), TAC Control (n ¼ 243) or TAC Elimination (n ¼ 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR þ Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference 2.2%, 97.5% confidence interval [CI] 8.8%, 4.4%). BPAR was less frequent in the EVR þ Reduced TAC group (6.1% vs. 13.3% in TAC Control, p ¼ 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR þ Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m2 (97.5% CI 1.9, 11.4 mL/min/1.73 m2, p¼ 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/ 1.73 m2 in the EVR þ Reduced TAC group and 66.1 (19.3) mL/min/1.73 m2 in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR þ Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.
Renal Function at Two Years in Liver Transplant Patients Receiving Everolimus: Results of a Randomized, Multicenter Study / F., Saliba1; *, ; P., De Simone2; F., Nevens3; L., De Carlis4; H. J., Metselaar5; S., Beckebaum6; 7, ; S., Jonas8; D., Sudan9; L., Fischer10; C., Duvoux11; K. D., Chavin12; B., Koneru13; M. A., Huang14; W. C., Chapman15; D., Foltys16; G., Dong17; P. M., Lopez18; J., Fung19; G., Junge18; Rossi, Massimo. - In: AMERICAN JOURNAL OF TRANSPLANTATION. - ISSN 1600-6135. - STAMPA. - 13(2013), pp. 1734-1745. [10.1111/ajt.12280]
Renal Function at Two Years in Liver Transplant Patients Receiving Everolimus: Results of a Randomized, Multicenter Study
ROSSI, MASSIMO
2013
Abstract
In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) þ Reduced tacrolimus (TAC; n ¼ 245), TAC Control (n ¼ 243) or TAC Elimination (n ¼ 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR þ Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference 2.2%, 97.5% confidence interval [CI] 8.8%, 4.4%). BPAR was less frequent in the EVR þ Reduced TAC group (6.1% vs. 13.3% in TAC Control, p ¼ 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR þ Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m2 (97.5% CI 1.9, 11.4 mL/min/1.73 m2, p¼ 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/ 1.73 m2 in the EVR þ Reduced TAC group and 66.1 (19.3) mL/min/1.73 m2 in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR þ Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.