Sirolimus/steroids Maintenance Therapy after Early Cyclosporine Withdrawal: 12-month Efficacy and Safety Results of Multicenter Single Arm Pilot Study in Primary Renal Allograft Recipients in Korea

ABSTRACT

PURPOSE: Sirolimus has potent anti-rejection activity as well as the ability to prolong allograft survival and reduce nephrotoxicity. This study was designed to evaluate the efficacy and safety of sirolimus in Korean de novo renal transplantation. METHODS: We included 79 patients who received sirolimus at nine Korean transplantation centers in the intention-to-treat and valid-for-safety analyses. The study was an open, single treatment arm multicenter trial with 12 months of patient follow-up. Initially, patients received 2 mg of sirolimus (after 6 mg of loading does) with cyclosporine and steroids. Sirolimus was administered for up to 12 months. Antibody induction was not used. At 3 months after transplantation, cyclosporine was progressively withdrawn over 4 to 8 weeks while sirolimus was adjusted to obtain trough concentrations within 15~30 ng/ml up to 6 months and concentrations within 12~24 ng/ml between 7 and 12 months. RESULTS: The proportion of patients who completed the 12-month sirolimus medication per protocol was 74.7% (59/79). Cyclosporine withdrawal was possible in 64 recipients (81.0%). Fifteen patients discontinued sirolimus before cyclosporine withdrawal, and 5 recipients did so after successful cyclosporine withdrawal. Most common causes of sirolimus discontinuation were graft rejection (n=8). Incidence of biopsy-proven acute rejection within 6 months after transplantation was 15.2%. Patient and graft survival rates at 12 months post transplantation were 97.5% and 96.2%, respectively. During the study period, three graft losses occurred by patient death. CONCLUSION: Based on this study, cyclosporine and sirolimus induction followed by cyclosporine withdrawal at 3 months post-transplant is considered to be efficient and safe after primary renal transplantation.