Journal article
Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study.
- Tedesco-Silva H Division of Nephrology, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil.
- Pascual J Department of Nephrology, Hospital del Mar, Barcelona, Spain.
- Viklicky O Department of Nephrology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
- Basic-Jukic N Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia.
- Cassuto E Department of Nephrology and Renal Transplantation, Hôpital Pasteur, Nice, France.
- Kim DY Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI.
- Cruzado JM Department of Nephrology, Hospital Universitari de Bellvitge, Barcelona, Spain.
- Sommerer C Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.
- Adel Bakr M Mansoura Urology and Nephrology Center, Mansoura, Egypt.
- Garcia VD Department of Renal Transplantation, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil.
- Uyen HD Department of Nephrology and Hypertension, Inselspital Bern, Bern, Switzerland.
- Russ G Central and Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, Australia.
- Soo Kim M Department of Transplantation Surgery, Severance Hospital Yonsei University Health System, Seoul, Republic of Korea.
- Kuypers D Department of Nephrology and Renal Transplantation, Gasthuisberg University Hospital, University of Leuven, Leuven, Belgium.
- Buchler M Department of Nephrology and Renal Transplantation, CHRU de Tours, Hôpital Bretonneau, Tours, France.
- Citterio F Policlinico Foundation, A Gemelli University, IRCCS, Catholic University of the Sacred Heart, Rome, Italy.
- Hernandez Gutierrez MP Research and Development, Novartis Pharma AG, Basel, Switzerland.
- Bernhardt P Research and Development, Novartis Pharma AG, Basel, Switzerland.
- Chadban S Department of Renal Medicine, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia.
- 2019-02-26
Published in:
- Transplantation. - 2019
Adult
Calcineurin Inhibitors
Cyclosporine
Drug Therapy, Combination
Everolimus
Graft Rejection
Graft Survival
Humans
Immunosuppressive Agents
Kidney Transplantation
Middle Aged
Mycophenolic Acid
Risk Factors
Tacrolimus
Time Factors
Treatment Outcome
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1097/TP.0000000000002626
- PMID 30801548
- Persistent URL
- https://folia.unifr.ch/global/documents/241984
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