Uemoto S, Abe R, Horike H, So M
Division of HBP Surgery and Transplantation, Kyoto University, Kyoto, Japan.
Medical Affairs, Astellas Pharma Inc., Tokyo, Japan.
Transplant Proc. 2014 Apr;46(3):749-53. doi: 10.1016/j.transproceed.2013.11.071.
Modified-release formulation of tacrolimus (TAC-MR) has been developed with the intent of improving patient adherence and quality of life. A number of studies have indicated that the efficacy and safety of once-daily TAC-MR were comparable with those of the original formulation, twice-daily tacrolimus. However, its dosage, trough level, safety, and efficacy in the multicenter clinical experience of Japanese liver transplant recipients have not been reported.
This postmarketing surveillance designed as an open-label, prospective, noninterventional observational study was performed. The 24 patients were enrolled for de novo transplantation, and the 122 patients were enrolled for conversion to TAC-MR from 22 medical institutions in Japan. The observation period is 1 year in de novo transplantation, and 24 weeks in conversion.
Regarding de novo transplant, the median daily TAC-MR dose was 0.041 mg/kg/d at 1 day after transplantation, and the median tacrolimus trough level was 5.5 ng/mL at 3 days after transplantation. The most common adverse drug reactions were infections, at an incidence rate of 25.0%. The most common infections were cytomegalovirus viremia, at an incidence rate of 12.5%. Both patient and graft survival rates at 1 year were 94.1% and the rejection rate was 20.8%. Regarding conversion to TAC-MR, the median daily conventional TAC dose before conversion was 1.8 mg/d, and the daily TAC-MR dose was 1.5 mg/d. The median TAC trough level was 3.6 ng/mL before conversion and 3.5 ng/mL 1 week after conversion. The most common adverse drug reactions were infections, at an incidence rate of 5.1%. Episodes of death or graft loss did not occur, and there were 3 episodes of rejection. After conversion to once-daily TAC-MR, the patients' adherence was improved.
This study shows that a TAC-MR-based immunosuppressive regimen is safe and effective as used in Japanese clinical practice.
他克莫司缓释制剂（TAC-MR）已被研发出来，旨在提高患者的依从性和生活质量。多项研究表明，每日一次的TAC-MR的疗效和安全性与原制剂、每日两次的他克莫司相当。然而，其在日本肝移植受者多中心临床经验中的剂量、谷浓度、安全性和疗效尚未见报道。
本上市后监测设计为一项开放标签、前瞻性、非干预性观察性研究。24例患者纳入初次移植，122例患者从日本22家医疗机构纳入由常规他克莫司转换为TAC-MR的研究。初次移植的观察期为1年，转换的观察期为24周。
关于初次移植，移植后1天TAC-MR的每日中位剂量为0.041mg/kg/d，移植后3天他克莫司谷浓度的中位值为5.5ng/mL。最常见的药物不良反应为感染，发生率为25.0%。最常见的感染为巨细胞病毒血症，发生率为12.5%。1年时患者和移植物存活率均为94.1%，排斥反应发生率为20.8%。关于转换为TAC-MR，转换前常规他克莫司的每日中位剂量为1.8mg/d，TAC-MR的每日剂量为1.5mg/d。转换前他克莫司谷浓度的中位值为3.6ng/mL，转换后1周为3.5ng/mL。最常见的药物不良反应为感染，发生率为5.1%。未发生死亡或移植物丢失事件，有3次排斥反应发作。转换为每日一次的TAC-MR后，患者的依从性得到改善。
本研究表明，基于TAC-MR的免疫抑制方案在日本临床实践中使用是安全有效的。
