Everolimus with reduced calcineurin inhibitor exposure in renal transplantation

• Verfasst von: Pascual, Julio [VerfasserIn]
• Verfasst von: Sommerer, Claudia [VerfasserIn]
• Titel: Everolimus with reduced calcineurin inhibitor exposure in renal transplantation
• Verf.angabe: Julio Pascual, Stefan P. Berger, Oliver Witzke, Helio Tedesco, Shamkant Mulgaonkar, Yasir Qazi, Steven Chadban, Federico Oppenheimer, Claudia Sommerer, Rainer Oberbauer, Yoshihiko Watarai, Christophe Legendre, Franco Citterio, Mitchell Henry, Titte R. Srinivas, Wen-Lin Luo, AnaMaria Marti, Peter Bernhardt, Flavio Vincenti, on behalf of the TRANSFORM Investigators
• E-Jahr: 2018
• Jahr: [2018]
• Umfang: 13 S.
• Illustrationen: Diagramme
• Fussnoten: Gesehen am 18.02.2020
• Titel Quelle: Enthalten in: American Society of NephrologyJournal of the American Society of Nephrology
• Ort Quelle: Washington, DC : American Society of Nephrology, 1990
• Jahr Quelle: 2018
• Band/Heft Quelle: 29(2018), 7, Seite 1979-1991
• ISSN Quelle: 1533-3450
• DOI: doi:10.1681/ASN.2018010009
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: calcineurin inhibitor
• Sach-SW: efficacy graft
• Sach-SW: everolimus
• Sach-SW: function
• Sach-SW: kidney transplantation
• Sach-SW: randomized
• K10plus-PPN: 1690290153

Abstract

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.