Author(s): De Simone P, Nevens F, De Carlis L, Metselaar HJ, Beckebaum S,
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Abstract In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7\% versus 9.7\% (-3.0\%; 95\% CI -8.7, 2.6\%; p<0.001 for noninferiority [12\% margin]). tBPAR occurred in 2.9\% of EVR+Reduced TAC patients versus 7.0\% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m(2) , 97.5\% CI 3.74, 13.27 mL/min/1.73 m(2) , p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7\% of EVR+Reduced TAC and 14.1\% of TAC Controls (relative risk 1.82, 95\% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95\% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
This article was published in Am J Transplant
and referenced in Pharmaceutica Analytica Acta