Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study

Franco Citterio, Helio Tedesco-Silva, Julio Pascual, Ondrej Viklicky, Nikolina Basic-Jukic, Elisabeth Cassuto, Dean Y. Kim, Josep M. Cruzado, Claudia Sommerer, Mohamed Adel Bakr, Valter D. Garcia, Huynh-Do Uyen, Graeme Russ, Myoung Soo Kim, Dirk Kuypers, Matthias Buchler, Maria Pilar Hernandez Gutierrez, Peter Bernhardt, Steve Chadban, Alan JardineTim Friede, Rafael Maldonado, Pablo Massari, Silvina Aleman, Silvia Maurich, Luis E. Gaite, Pablo Raffaele, Nora Imperiali, Scott Campbell, Steve Chadban, Peter Hughes, Ashley Irish, John Kanellis, Wai Lim, Philip J. O'Connell, Graeme Russ, Zoltan Endre, Peter Mount, Paul Hengster, Peter Neudorfer, Rainer Oberbauer, Johann Pratschke, Dirk Kuypers, Jean-Louis Bosmans, Emine N. Broeders, Laurent Weekers, Helio Tedesco Silva, Elias D. Neto, Valter D. Garcia, Emil P. Dimitrov, Alvaro Kompatzki, Carlos Benavides, Johanna Schweineberg, Nikolina Basic-Jukic, Mladen Knotek, Sanjin Racki, Ondrej Viklicky, Mohamed Adel Bakr, Christophe Legendre, Elisabeth Cassuto, Vincent Pernin, Vincent Vuiblet, Matthias Buchler, Claudia Sommerer, Peter Weithofer, Thomas Rath, Oliver Witzke, Markus Van Der Giet, Wolfgang Arns, Lutz Renders, Antje Habicht, Daniel Seehofer, Bernhard Banas, Frank Lehner, Johann Pratschke, Rainer Oberbauer, Martin Zeier, Ioannis Boletis, Dimitrios Goumenos, Vasileios Papanikolaou, Spyros Drakopoulos, Dinesh Khullar, Veerbhadra Guptha, Shibu Jacob, Alan Fernandes Almeida, Eytan Mor, Richard Nakache, Mario Carmellini, Paolo Rigotti, Giacomo Colussi, Giuseppe Tisone, Paola Todeschini, Luigi Biancone, Vincenzo Cantaluppi, Loreto Gesualdo, Umberto Maggiore, Yoshihiko Watarai, Naotake Akutsu, Takashi Kenmochi, Duck Jong Han, Myoung Soo Kim, Sung Joo Kim, Torki Alotaibi, Dania Chelala, Hilal Abou Zeinab, Khalil Jaber, Ghazali Ahmad Kutty, Hin Seng Wong, Francisco Javier Monteon Ramos, J. W. De Fijter, S. P. Berger, F. J. Bemelman, A. D. Van Zuilen, L. Hilbrands, M. H.L. Christiaans, Anders Hartmann, Romina Danguilan, Angel Joaquin Amante, Kazimierz Ciechanowski, Maciej Glyda, Marek Karczewski, Alicja Debska-Slizien, Fernando Nolasco, Jose Guerra, Joana Santos, Patricia Joao Matias, Arnaldo Figueiredo, Yan G. Moysyuk, Aleksey V. Pinchuk, Ilya V. Aleksandrov, Vladimir E. Zagainov, Elena I. Boretskaya, Vladimir L. Medvedev, Ashraf Attia, Wael Habhab, Meteb Bugami, Neven Vavic, Igor Mitic, Goran Paunovic, Terence Kee, Tatiana Baltesova, Eva Lackova, Zuzana Zilinska, Ivana Dedinska, Miha Arnol, Elmi Muller, Julio Pascual, Frederic Oppenheimer, Asuncion Sancho, Alex Gutierrez Dalmau, Domingo Marrero, Josep M. Cruzado, Amado Andres Belmonte, Juan Carlos Ruiz San Millan, Antonio Osuna, Ana Fernandez, Lars Wennberg, Bengt Von Zur Muhlen, Bengt Gustafsson, Uyen Huynh-Do, Meng-Kun Tsai, Ming Ju Wu, Tsung Ching Chou, Prajej Ruangkanchanasetr, Sakarn Bunnag, Atiporn Ingsathit, Aydin Turmen, Ahmet V. Celik, Huseyin Kocak, Alexander Wiseman, Phillippe Gauthier, Fuad Shihab, Stevenson Bynon, Bernard Fischbach, Goran B. Klintmalm, Richard Knight, Kenneth L. Brayman, Jason Wellen, Stanley J. Jordan, Yasir Qazi, Ronald Cotton, Venkat Peddi, David Leeser, Mohamed E. Akoad, Shamkant Mulgaonkar, Martha Pavlakis, Reginald Gohh, Charles Bratton, Nahel Elias, Debra Sudan, Mary Waybill, Johnny Hong, Silas Norman, Ivo Tzvetanov, Dean Y. Kim, Mitchell Henry, Jeffrey Rogers, Chandrasekar Santhanakrishnan, Nicolae Leca, Tomasz Kozlowski, Flavio Vincenti, Enver Akalin, Clifton E. Kew, David Shaffer, Liise K. Kayler, Steven Steinberg, Stuart M. Flechner, Donald Hricik, Michael De Vera, Didier Mandelbrot

Risultato della ricerca: Contributo in rivistaArticolo in rivista

28 Citazioni (Scopus)

Abstract

BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.
Lingua originaleEnglish
pagine (da-a)1953-1963
Numero di pagine11
RivistaTransplantation
Volume103
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • everolimus

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