USE OF MTOR INHIBITORS AND MPA I

T. Becker¹, W. Arns², K. Budde³, F. Pietruck⁴, U. Eisenberger⁵, W. Fischer⁶, S. Kramer⁶, C. Sommerer⁷, P. Reinke^8
1Department General-, Viszeral- And Transplantsurgery, Hanover Medical School, Hanover/GERMANY, ², Transplantationszentrum, Koeln-Merheim/GERMANY, ³, University Hospital Charité, Berlin/GERMANY, ⁴Abteilung Nieren-undhochdruckkranke, Universitätsklinikum Essen, Essen/GERMANY, ⁵Inselspital, Departement of Nephrology and Hypertension, Bern/SWITZERLAND, ⁶, Novartis Pharma, Nuremberg/GERMANY, ⁷, Nierenzentrum, Heidelberg/GERMANY, ⁸Department Of Nephrology And Intensive Care Ccv, Charité-Universitätsmedizin Berlin, Berlin/GERMANY

Body: Aim of the study: To follow-up on renal function, efficacy and safety after a conversion to an Everolimus/Enteric-coated mycophenolate sodium (EC-MPS) regimen after Cyclosporine (CsA) withdrawal in de novo kidney allograft recipients at month (Mo) 24 post transplantation. Methods: In this prospective, open-label, controlled, multi-center study renal allograft recipients were randomized to an immunosuppressive regimen consisting of either Everolimus/EC-MPS or CsA/EC-MPS at Mo 4.5 after transplantation. After completion of the core study at Mo 12, patients were included in an observational 12-Mo follow up study. Results: 300 pts were randomized to either Everolimus/EC-MPS (n=155) or CsA/EC-MPS (n=145), 244 (81.3%) pts completed the 24 month visit. Renal function expressed as calculated GFR (Nankivell method) was similar in both groups at baseline (randomization 4.5 Mo post tx) with an improvement by 7.16 mL/min/1.73m² in favor of the Everolimus/EC-MPS regimen (p=0.017) at Mo 24 (61.7 ± 17.1 vs. 68.9 ± 19.4 mL/min/1.73m²) The observed GFR slope from randomization to Mo 24 was +6.7 [+3.2,+10.2] for Everolimus/EC-MPS and -0.8 [-4.5,+2.9] mL/min/1.73m² for CsA/EC-MPS pts. Fewer pts in the Everolimus group had a decline of GFR compared to renal function at randomization (Nankivell: 24.7% vs 41.4%; p=0.0034) compared with Cyclosporine. BPAR was reported in 17 (11.0%) Everolimus/EC-MPS-treated vs. 7 (4.8%) CsA/EC-MPS treated patients between randomization and Mo 24. After 12 months two additional BPAR occurred in each group. Three death and one graft loss was observed in the CsA/EC-MPS group none in the Everolimus group. The number of patients with infections (35 pts (22.6%) in the Everolimus vs. 30 pts (20.7%) in the CsA group) and hospitalization (43 pts (27.7%) in the Everolimus vs. 51 pts (35.2%) in the CsA group) in the follow-up period (Mo 12 to Mo 24) was comparable in both groups. Conclusions: The conversion to Everolimus/EC-MPS in de novo renal transplant patients after CNI withdrawal early after transplantation reflects a novel therapeutic approach which significantly maintains renal function over a period of 24 months without compromising efficacy and safety.

Disclosure: All authors have declared no conflicts of interest.