Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation.

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 and TRANSFORM, Investigators (2018). Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation. Journal of the American Society of Nephrology : JASN, 29(7), pp. 1979-1991. American Society of Nephrology 10.1681/ASN.2018010009

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Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. In a multicenter noninferiority trial, we randomized 2037 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 m at post-transplant month 12 using a 10% noninferiority margin. In the intent-to-treat population (everolimus =1022, MPA =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%). 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. 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
ISSN:	1533-3450
Publisher:	American Society of Nephrology
Language:	English
Submitter:	Uyen Huynh-Do
Date Deposited:	17 Sep 2019 13:33
Last Modified:	17 Sep 2019 13:33
Publisher DOI:	10.1681/ASN.2018010009
PubMed ID:	29752413
Additional Information:	Uyen Huynh-Do collaborator of TRANSFORM Investigators
Uncontrolled Keywords:	calcineurin inhibitor efficacy graft everolimus function kidney transplantation randomized
URI:	https://boris.unibe.ch/id/eprint/131734