Everolimus and Minimization of Cyclosporine in Renal Transplantation: 24-Month Follow-Up of the EVEREST Study

The association of cyclosporine A (CsA) with everolimus can exert synergistic effects on the alloimmune response. CsA inhibits the synthesis of interleukin-2 while everolimus inhibits the response to interleukin-2. Moreover, the interaction with CsA increases the bioavailability of everolimus (1). These data suggest that it is possible to reduce the doses of both drugs when given in combination. Previously, we reported the 1-year results of a randomized trial in 285 de novo renal transplants, 278 from deceased donors (2). Patients of group A received low-concentration CsA (C2 maintenance levels 350–500 ng/mL) plus everolimus (C0 levels 3–8 ng/mL), while patients of group B received very low-concentration CsA (C2 maintenance levels 150–300 ng/mL) and everolimus at higher target levels (C0 8–12 ng/mL). One-year graft survival rate was better in group B (98% vs. 90%; P=0.007). The mean serum creatinine levels at 1 year were, respectively, 1.51±0.55 mg/dL and 1.55±0.62 mg/dL. After the 1-year study was completed, 215 patients (110 in group A and 115 in group B) accepted to enter the extension study and to continue the study treatment up to 2 years. At 24 months, the mean everolimus dosages were 1.45±0.6 mg/day in group A (blood levels 6.17±2.1 ng/mL) and 2.24±1.1 mg/day in group B (blood levels 8.15±3.5 ng/mL), and the dosages of CsA were 1.62±0.5 mg/kg/day (C2 levels 407.6±159 ng/mL) and 1.38±0.7 mg/kg/day (C2 blood levels 330.7±159 ng/mL), respectively; the prednisone dosages were 5.14±1.28 mg/day in group A and 4.91±1.10 mg/day in group B.