Conversion From Cyclosporine to Everolimus at 4.5 Months Posttransplant: 3‐Year Results From the Randomized ZEUS Study

• Published in: American journal of transplantation Vol. 12; no. 6; pp. 1528 - 1540
• Main Authors: Budde, K., Lehner, F., Sommerer, C., Arns, W., Reinke, P., Eisenberger, U., Wüthrich, R. P., Scheidl, S., May, C., Paulus, E.‐M., Mühlfeld, A., Wolters, H. H., Pressmar, K., Stahl, R., Witzke, O.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.06.2012; Wiley
• Subjects: Adolescent; Adult; Aged; Analysis of Variance; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Calcineurin inhibitor; conversion; cyclosporine; Cyclosporine - administration & dosage; Everolimus; Humans; Immunosuppressive Agents - administration & dosage; Kidney Transplantation; Medical sciences; Middle Aged; mTOR inhibitor; Pharmacology. Drug treatments; Sirolimus - administration & dosage; Sirolimus - analogs & derivatives; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Young Adult; Zeus; ZEUS study; ZEUS study; cyclosporine; Calcineurin inhibitor; Prognosis; Lactone; Transplantation; Homotransplantation; Macrolide; Conversion; Long term; Drug conversion; Randomization; Treatment; Surgery; mTOR inhibitor; Graft; Clinical trial; Ciclosporin; Protein synthesis inhibitor; Immunosuppressive agent; Antibacterial agent; Everolimus
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2012.03994.x

The long‐term effect of conversion from calcineurin inhibitor (CNI) therapy to an mTOR inhibitor requires clarification. Following completion of the 12‐month, open‐label, multicenter ZEUS study, in which 300 kidney transplant recipients were randomized to continue cyclosporine (CsA) or convert to everolimus at 4.5 months posttransplant, outcomes were assessed at month 36 (n = 284; 94.7%). CNI therapy was reintroduced in 28.4% of everolimus patients by month 36. The primary efficacy endpoint, estimated glomerular filtration rate (Nankivell, ANCOVA) was significantly higher with everolimus versus the CsA group at month 24 (7.6 mL/min/1.73 m2, 95%CI 4.3, 11.0 mL/min/1.73 m2; p < 0.001) and month 36 (7.5 mL/min/1.73 m2, 95%CI 3.6, 11.4 mL/min/1.73 m2; p < 0.001). The incidence of biopsy‐proven acute rejection from randomization to month 36 was 13.0% in the everolimus arm and 4.8% in the CsA arm (p = 0.015). Patient and graft survival, as well as incidences of malignancy, severe infections and hospitalization, were similar between groups. Kidney transplant patients who are converted from CsA to everolimus at month 4.5 and who remain on everolimus thereafter may achieve a significant improvement in renal function that is maintained to 3 years. There was a significantly higher rate of rejection in the everolimus arm but this did not exert a deleterious effect by 3 years posttransplant. Follow‐up data from the ZEUS study, in which kidney transplant recipients were randomized to remain on cyclosporine or convert to everolimus, show that patients who continue to receive everolimus maintain a significant improvement in renal function to 3 years despite a significantly higher rate of biopsy‐proven acute rejection.