Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial

Budde, Klemens; Becker, Thomas; Arns, Wolfgang; Sommerer, Claudia; Reinke, Petra; Eisenberger, Ute; Krämer, Stefan; Fischer, Wolfgang; Gschaidmeier, Harald; Pietruck, Frank

doi:10.1016/s0140-6736(10)62318-5

Cited by 336 publications

(312 citation statements)

References 33 publications

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“…This range is based primarily on the use of everolimus for immunosuppression 19, 20, 21. This is noteworthy given initial concerns about the ability of mTOR inhibitors to cross the blood–brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis

Franz

Agricola

Mays

et al. 2015

Annals of Neurology

146

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ObjectiveTo analyze the cumulative efficacy and safety of everolimus in treating subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC) from an open‐label phase II study (NCT00411619). Updated data became available from the conclusion of the extension phase and are presented in this ≥5‐year analysis.MethodsPatients aged ≥ 3 years with a definite diagnosis of TSC and increasing SEGA lesion size (≥2 magnetic resonance imaging scans) received everolimus starting at 3mg/m2/day (titrated to target blood trough levels of 5–15ng/ml). The primary efficacy endpoint was reduction from baseline in primary SEGA volume.ResultsAs of the study completion date (January 28, 2014), 22 of 28 (78.6%) initially enrolled patients finished the study per protocol. Median (range) duration of exposure to everolimus was 67.8 (4.7–83.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA volume reductions of ≥50% and ≥30% relative to baseline, respectively, after 60 months of treatment. The proportion of patients experiencing daily seizures was reduced from 7 of 26 (26.9%) patients at baseline to 2 of 18 (11.1%) patients at month 60. Most commonly reported adverse events (AEs) were upper respiratory tract infection and stomatitis of mostly grade 1 or 2 severity. No patient discontinued treatment due to AEs. The frequency of emergence of most AEs decreased over the course of the study.InterpretationEverolimus continues to demonstrate a sustained effect on SEGA tumor reduction over ≥5 years of treatment. Everolimus remained well‐tolerated, and no new safety concerns were noted. Ann Neurol 2015;78:929–938

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Section: Discussionmentioning

confidence: 99%

Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis

Franz

Agricola

Mays

et al. 2015

Annals of Neurology

146

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“…In addition, 6 deaths and 7 graft losses were documented in the remained 37 patients, such that outcomes were recorded in 245/269 patients (91.1%) who entered the follow-up phase. The demographic characteristics of the follow-up population (Table 1) were similar to the core study population (18).…”

Section: Patient Populationmentioning

confidence: 92%

“…Estimated GFR (eGFR) was calculated according to the Nankivell (23), and MDRD (25) formulae. The primary efficacy end point was eGFR (Nankivell) at month 12, assessed by analysis of covariance (ANCOVA) with treatment, center and donor type as factors, and eGFR at month 4.5 as a covariate, using the last observation carried forward (LOCF) method for missing values (18), that is irrespective of whether one or more components of the calculated GFR were missing, the calculated GFR value of the previous visit was substituted. This analysis was repeated for data collected at the annual follow-up visits.…”

Section: Methodsmentioning

confidence: 99%

“…Results have demonstrated that immunosuppressive efficacy is maintained, but although an improvement in graft function has been observed (13) a significant difference may not be sustained (17). Evidence from a series of randomized studies indicates that longer-term renal benefit may be achieved if an mTOR inhibitor is introduced and CNI therapy is withdrawn during the first 6 months after kidney transplantation (18)(19)(20)(21), before extensive, irreversible CNI-related nephrotoxicity develops (2).…”

Section: Introductionmentioning

confidence: 99%

“…After completion of the 12-month study (18), patients underwent annual follow-up assessments for 5 years posttransplant. Results at 3 years have been published previously (22).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Five-Year Outcomes in Kidney Transplant Patients Converted From Cyclosporine to Everolimus: The Randomized ZEUS Study

Budde

Lehner

Sommerer

et al. 2015

American Journal of Transplantation

118

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Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients

Karpe

Talaulikar

Walters

2017

Cochrane Database of Systematic Reviews

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CNI avoidance increased acute rejection and CNI withdrawal increases acute rejection but reduced graft loss at least over the short-term. Low dose CNI with induction regimens reduced acute rejection and graft loss with no major adverse events, also in the short-term. The use of mTOR-I reduced CMV infections but increased the risk of acute rejection. These conclusions must be tempered by the lack of long-term data in most of the studies, particularly with regards to chronic antibody-mediated rejection, and the suboptimal methodological quality of the included studies.

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Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial

Cited by 336 publications

References 33 publications

Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis

Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis

Five-Year Outcomes in Kidney Transplant Patients Converted From Cyclosporine to Everolimus: The Randomized ZEUS Study

Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients

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