Kim Myoung Soo, Joh Jae-Won, Kim Dong-Sik, Kim Seoung Hoon, Choi Jin Sub, Lee Jaegeun, Lee Jee Youn, Kim Jong Man, Kwon Choon Hyuck David, Choi Gyu-Seong, Yu Young Dong, Yoon Yong-In, Han Jae Hyun, Lee Yun Jeong, Jiang Hongsi, Kim Soon-Il
Department of Transplant Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Surgery, Samsung Medical Center, Seoul, Korea.
Korean J Transplant. 2019 Jun 30;33(2):20-29. doi: 10.4285/jkstn.2019.33.2.20.
Prolonged-release tacrolimus is associated with better long-term graft and patient survival than the immediate-release formulation in liver transplant patients. However, no clinical data are available to assess the efficacy and safety of early conversion from twice-daily, immediate-release tacrolimus to once-daily, prolonged-release tacrolimus in liver transplant recipients in Korea.
A 24-week, randomized, open-label study was conducted in 36 liver transplant recipients. All patients received immediate- release tacrolimus (0.1-0.2 mg/kg/day, divided into two doses) for 4 weeks after transplantation, at which time 50% of the patients were converted, at a ratio of 1 mg to 1 mg, to prolonged-release tacrolimus (once-daily). The primary efficacy endpoint was the incidence of biopsy-confirmed acute rejection (BCAR) from weeks 4 to 24 after transplantation (per-protocol set). Medication adherence, adverse event profiles, laboratory tests, vital signs, and physical changes were also recorded.
BCAR frequency at 24 weeks was similar between the two treatment groups; two cases (mean±standard deviation, 0.14±0.53 cases) of BCAR were reported in one patient treated with prolonged-release tacrolimus (n=14), while no such cases were reported among patients treated with immediate-release tacrolimus (n=12). The tacrolimus blood concentration at weeks 12 and 24, medication adherence, and adverse event profiles were also similar between the formulations, with no unusual laboratory test results, vital signs, or physical changes reported.
Early conversion to a simplified, once-daily, prolonged-release tacrolimus regimen may be an effective treatment option for liver transplant recipients in Korea. Larger-scale studies are warranted to confirm non-inferiority to immediate-release tacrolimus formulation in liver transplant recipients.
在肝移植患者中，与速释剂型他克莫司相比，缓释剂型他克莫司与更好的长期移植物和患者生存率相关。然而，在韩国肝移植受者中，尚无临床数据可评估从每日两次速释他克莫司早期转换为每日一次缓释他克莫司的疗效和安全性。
对36例肝移植受者进行了一项为期24周的随机开放标签研究。所有患者在移植后接受速释他克莫司（0.1 - 0.2 mg/kg/天，分两次给药）4周，此时50%的患者以1 mg比1 mg的比例转换为缓释他克莫司（每日一次）。主要疗效终点是移植后第4周至24周活检证实的急性排斥反应（BCAR）发生率（符合方案集）。还记录了药物依从性、不良事件谱、实验室检查、生命体征和身体变化。
两个治疗组在24周时的BCAR频率相似；接受缓释他克莫司治疗的14例患者中有2例（平均值±标准差，0.14±0.53例）报告了BCAR，而接受速释他克莫司治疗的12例患者中未报告此类病例。两种剂型在第12周和24周时的他克莫司血药浓度、药物依从性和不良事件谱也相似，未报告异常的实验室检查结果、生命体征或身体变化。
早期转换为简化的每日一次缓释他克莫司方案可能是韩国肝移植受者的一种有效治疗选择。需要进行更大规模的研究以证实其在肝移植受者中不劣于速释他克莫司剂型。
