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Safety of everolimus with reduced calcineurin inhibitor exposure in de novo kidney transplants: an analysis from the randomized TRANSFORM study

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...

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Main Authors: Tedesco-Silva, Helio (Author) , Pascual, Julio (Author) , Viklicky, Ondrej (Author) , Basic-Jukic, Nikolina (Author) , Cassuto, Elisabeth (Author) , Kim, Dean Y. (Author) , Cruzado, Josep M. (Author) , Sommerer, Claudia (Author) , Adel Bakr, Mohamed (Author) , Garcia, Valter D. (Author) , Uyen, Huynh-Do (Author) , Russ, Graeme (Author) , Soo Kim, Myoung (Author) , Kuypers, Dirk (Author) , Buchler, Matthias (Author) , Citterio, Franco (Author) , Hernandez Gutierrez, Maria Pilar (Author) , Bernhardt, Peter (Author) , Chadban, Steve (Author)
Format: Article (Journal)
Language:English
Published: September 2019
In: Transplantation
Year: 2019, Volume: 103, Issue: 9, Pages: 1953-1963
ISSN:1534-6080
DOI:10.1097/TP.0000000000002626
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/TP.0000000000002626
Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/transplantjournal/Fulltext/2019/09000/Safety_of_Everolimus_With_Reduced_Calcineurin.36.aspx
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Author Notes: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, Franco Citterio, Maria Pilar Hernandez Gutierrez, Peter Bernhardt, and Steve Chadban, on behalf of the TRANSFORM Investigators
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Summary: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.
Item Description:Gesehen am 21.04.2020
Physical Description:Online Resource
ISSN:1534-6080
DOI:10.1097/TP.0000000000002626

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