TY - JOUR
T1 - Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study
AU - Berger, Stefan P.
AU - Sommerer, Claudia
AU - Witzke, Oliver
AU - Tedesco, Helio
AU - Chadban, Steve
AU - Mulgaonkar, Shamkant
AU - Qazi, Yasir
AU - De Fijter, Johan W.
AU - Oppenheimer, Federico
AU - Cruzado, Josep M.
AU - Watarai, Yoshihiko
AU - Massari, Pablo
AU - Massari, Pietro
AU - Legendre, Christophe
AU - Citterio, Franco
AU - Henry, Mitchell
AU - Srinivas, Titte R.
AU - Vincenti, Flavio
AU - Gutierrez, Maria Pilar Hernandez
AU - Marti, Ana Maria
AU - Bernhardt, Peter
AU - Pascual, Julio
PY - 2019
Y1 - 2019
N2 - TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m2 was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = −0.3, 8.7; P =.006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m2) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R− high-risk group (P <.0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24 months. Clinicaltrials.gov number: NCT01950819.
AB - TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m2 was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = −0.3, 8.7; P =.006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m2) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R− high-risk group (P <.0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24 months. Clinicaltrials.gov number: NCT01950819.
KW - Calcineurin Inhibitors
KW - Everolimus
KW - Female
KW - Follow-Up Studies
KW - Graft Rejection
KW - Graft Survival
KW - Humans
KW - Immunosuppressive Agents
KW - Kidney Failure, Chronic
KW - Kidney Transplantation
KW - Male
KW - Middle Aged
KW - Postoperative Complications
KW - Prognosis
KW - Prospective Studies
KW - Risk Factors
KW - Survival Rate
KW - clinical research/practice
KW - immunosuppressant - mechanistic target of rapamycin (mTOR)
KW - immunosuppressant - mechanistic target of rapamycin: everolimus
KW - immunosuppression/immune modulation
KW - immunosuppressive regimens - minimization/withdrawal
KW - kidney transplantation/nephrology
KW - liver transplantation/hepatology
KW - Calcineurin Inhibitors
KW - Everolimus
KW - Female
KW - Follow-Up Studies
KW - Graft Rejection
KW - Graft Survival
KW - Humans
KW - Immunosuppressive Agents
KW - Kidney Failure, Chronic
KW - Kidney Transplantation
KW - Male
KW - Middle Aged
KW - Postoperative Complications
KW - Prognosis
KW - Prospective Studies
KW - Risk Factors
KW - Survival Rate
KW - clinical research/practice
KW - immunosuppressant - mechanistic target of rapamycin (mTOR)
KW - immunosuppressant - mechanistic target of rapamycin: everolimus
KW - immunosuppression/immune modulation
KW - immunosuppressive regimens - minimization/withdrawal
KW - kidney transplantation/nephrology
KW - liver transplantation/hepatology
UR - http://hdl.handle.net/10807/170051
U2 - 10.1111/ajt.15480
DO - 10.1111/ajt.15480
M3 - Article
SN - 1600-6135
VL - 19
SP - 3018
EP - 3034
JO - American Journal of Transplantation
JF - American Journal of Transplantation
ER -