Objective: Assessment of renal function, safety and efficacy of an Everolimus (EVE) regimen after Calcineurin-Inhibitor (CNI) withdrawal in maintenance kidney allograft recipients.

Methods: In an open-label, randomized, controlled, multi-center study 93 patients (pts) on a stable immunosuppressive therapy consisting of CNI, Enteric-Coated Mycophenolate Sodium (EC-MPS) with or without corticosteroids were randomized to either continue CNI treatment + EC-MPS or convert to an EVE + EC-MPS based regimen. After completion of the core study at Mo12, pts were included in an observational follow-up (FU) study.

Results: 93 pts with a mean time of 6.4years since the most recent transplantation (Tx) were randomized to either EVE (n=46) or CNI (n=47) treatment, 72(77.4%) pts of whom completed 48Mo visit. Mean trough levels were 84±44ng/ml in CsA, 5.9±2.4ng/ml in Tacrolimus and 6.7±2.0ng/ml in EVE treated pts. At Mo48 after randomization mean adjusted GFR (Nankivell) in ITT pts was higher by +5.6 mL/min/1.73m²(95%CI:[-0.6;+11.8];p=0.08) for the EVE compared to the CNI group. The observed adjusted mean GFR change from conversion to Mo48 was +5.7(95%CI:[-0.1;+11.5]) for EVE and +0.1(95%CI:[-5.1;+5.3])mL/min/1.73m² for CNI pts (p=0.08). Mean eGFR of patients who remained on the assigned EVE treatment was higher by +8.7ml/min(95%CI:[+16.0;+1.4]n=20;p=0.02) compared to CNI pts (n=31) at Mo48 with an observed mean GFR change to Mo48 of +8.0±8.1 for pts on EVE vs -0.6±14.5ml/min in CNI group. In the EVE group 24(52.2%) pts had improved GFR whereas only 17(36.2%) in the CNI group (ITT;p=0.08). 2 deaths and 1 graft loss were observed in the CNI group, 1 death and 3 graft losses in the EVE group and no BPAR in either group. The overall number of pts with any infections after 12Mo was 23(50.0%) for EVE vs 20(42.6%) for CsA group, with only 3(6.5%) of them for EVE group and 1(2.1%) for CNI group reported as being severe but none leading to hospitalization. No malignancy occurred in the EVE group compared to 1(2.1%) in the CNI group.

Conclusions: The late conversion to an EVE/EC-MPS treatment in maintenance renal Tx patients after CNI withdrawal is safe and associated with a tendency towards better renal function maintained even after 4 years.

Budde, K.: Other, Novartis, Research Funds and/or Trial Honoraria, Roche, Research Funds and/or Trial Honoraria, Pfizer, Research Funds and/or Trial Honoraria, Astellas, Research Funds and/or Trial Honoraria, Bristol-Myers Squibb, Research Funds and/or Trial Honoraria, Hexal, Research Funds and/or Trial Honoraria. Sommerer, C.: Other, Novartis, Honoraria, Astellas, Honoraria. Haller, H.: Other, Amgen, Honoraria for Speakers/Chairmanship at Meetings, Astra-Zeneca, Honoraria for Speakers/Chairmanship at Meetings, Bristol-Myers Squibb, Honoraria for Speakers/Chairmanship at Meetings, Novartis, Consultancy and Honoraria Speakers/Chairmanship, Roche, Consultancy and Honoraria Speakers/Chairmanship, Sanofi-Aventis, Consultancy and Honoraria Speakers/Chairmanship. Arns, W.: Other, Novartis, Study Honoraria, Roche, Study Honoraria, Pfizer, Study Honoraria, Astellas, Study Honoraria. Witzke, O.: Other, Novartis, Honoraria, Research Funds, Speakers Fee, Roche, Honoraria, Research Funds, Speakers Fee, Teva, Honoraria and Speakers Fee, Astellas, Honoraria and Speakers Fee. Suwelack, B.: Other, Novartis Pharma, Honoraria, Roche, Fee, Astellas, Fee, BMS, Fee. May, C.: Employee, Novartis Pharma. Baeumer, D.: Employee, Novartis Pharma. Paulus, E.: Employee, Novartis Pharma. Rath, T.: Other, Novartis, Honoraria/Speaker Fee and Research Grant, Roche, Honoraria, Speaker Fee and Research Grant, Teva, Honoraria and Speaker Fee, Astellas, Honoraria and Speaker Fee.

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