Naslov
Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation

Autori
Pascual, Julio ; Berger, Stefan P. ; Witzke, Oliver ; Tedesco, Helio ; Mulgaonkar, Shamkant ; Qazi, Yasir ; Chadban, Steven ; Oppenheimer, Federico ; Sommerer, Claudia ; Oberbauer, Rainer ; Watarai, Yoshihiko ; Legendre, Christophe ; Citterio, Franco ; Henry, Mitchell ; Srinivas, Titte R. ; Luo, Wen-Lin ; Marti, AnaMaria ; Bernhardt, Peter ; Vincenti, Flavio ; on behalf of the TRANSFORM Investigators ; Knotek, Mladen ; Bašić Jukić, Nikolina

Izvornik
Journal of the American Society of Nephrology (1046-6673) 29 (2018), 7; 1979-1991

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
calcineurin inhibitor ; efficacy graft ; everolimus ; function ; kidney transplantation ; randomized

Sažetak
Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post- transplant month 12 using a 10% noninferiority margin.Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2% ; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post- transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3% ; 95% confidence interval, -1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody- mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.

Izvorni jezik
Engleski

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