Recommendations for the use of everolimus in de novo kidney transplantation: False beliefs, myths and realities

Pascual, Julio; Diekmann, Fritz; Fernández-Rivera, Constantino; Marqués, Gonzalo Gómez; Gutiérrez-Dalmau, Álex; Pérez‐Sáez, María José; Sancho-Calabuig, Asunción; Oppenheimer, Federico

doi:10.1016/j.nefroe.2017.04.016

Cited by 10 publications

(12 citation statements)

References 76 publications

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“…15 This trend indicates a general tendency toward discontinuing EVR or switching to standard CNI more readily than adjusting EVR dose to manage related AEs. 32 Consistent with previous studies, the EVR + rCNI regimen offered significant protection from viral infections up to 24 months, 14,15,[17][18][19][20]22,26,36 thereby confirming the antiviral effect of EVR even in the presence of TAC levels above target range. Of interest, the CMV incidence was also significantly lower with EVR + rCNI in high-risk (D+/R−) patients.…”

Section: Ta B L E 4 Efficacysupporting

confidence: 88%

“…[29][30][31] However, prospective studies evaluating the association between de novo EVR use and the development of dnDSA are scarce. 32 Our results corroborate that de novo EVR with reduced-exposure CNI is not associated with a higher incidence of dnDSA compared to standard-of-care up to 2 years posttransplantation. Despite a low number of evaluable patients at month 24, we believe that occurrence of dnDSA with the EVR + rCNI regimen does not translate into a high risk of acute and chronic ABMR and acute rejections as evident from the low and comparable incidence of these events between the 2 treatment arms.…”

Section: Ta B L E 4 Efficacysupporting

confidence: 83%

“…Conflicting reports exist in the literature about the association of mTORi with development of dnDSA; while early or late conversion from CNI to EVR was associated with higher risk of dnDSA, EVR as a maintenance therapy with low‐dose CNI does not increase the risk . However, prospective studies evaluating the association between de novo EVR use and the development of dnDSA are scarce . Our results corroborate that de novo EVR with reduced‐exposure CNI is not associated with a higher incidence of dnDSA compared to standard‐of‐care up to 2 years posttransplantation.…”

Section: Discussionmentioning

confidence: 99%

“…A similar trend toward higher discontinuation due to AEs with the EVR + rCNI regimen was observed in the A2309 study at month 24 . This trend indicates a general tendency toward discontinuing EVR or switching to standard CNI more readily than adjusting EVR dose to manage related AEs …”

Section: Discussionmentioning

confidence: 99%

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Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study

Berger

Sommerer

Witzke

et al. 2019

American Journal of Transplantation

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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.

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Section: Ta B L E 4 Efficacysupporting

confidence: 88%

Section: Ta B L E 4 Efficacysupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study

Berger

Sommerer

Witzke

et al. 2019

American Journal of Transplantation

Self Cite

120

117

View full text Add to dashboard Cite

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“… The use of concomitant medication such as angiotensin receptor antagonists should be considered before switching immunosuppressive regimens [50].…”

Section: Accepted Manuscriptmentioning

confidence: 99%