Corticosteroid-Sparing and Optimization of Mycophenolic Acid Exposure in Liver Transplant Recipients Receiving Mycophenolate Mofetil and Tacrolimus: A Randomized, Multicenter Study
Corticosteroid-Sparing and Optimization of Mycophenolic Acid Exposure in Liver Transplant Recipients Receiving Mycophenolate Mofetil and Tacrolimus: A Randomized, Multicenter Study
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DOI：
10.1097/tp.0000000000001228
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发表时间：
2016-08-01
期刊：
影响因子：
6.2
通讯作者：
Marquet, Pierre
中科院分区：
文献类型：
--
作者：
Saliba, Faouzi;Rostaing, Lionel;Marquet, Pierre
背景。我们在新肝移植受者中进行了一项随机多中心开放标签试验，以评估无皮质类固醇（CS）方案联合他克莫司（Tac）和剂量强化霉酚酸酯（MMF）进一步单独调整的可行性和潜在益处。方法。成人肝移植受者在移植当天随机分为无CS方案，Tac和MMF从3g /d开始，根据霉酚酸（MPA）暴露量从第5天开始调整剂量（a组），或CS维持至6个月，Tac和固定剂量MMF (2g /d) （B组）。主要终点是移植后第一年经历经活检证实的急性排斥反应（BPAR）的患者比例。结果。187例患者被随机分组，其中174例为按方案人群（每组87例）。非劣效性的主要目标得到了满足：A组7名患者（8%）和b组8名患者（9%）在第一年接受了BPAR治疗。A组2例（2%）和B组5例（6%）患者失去移植物，两组患者12个月生存率相似（90.8% vs 89.8%; P = 0.86）。不良事件在两组之间是相似的，除了新发糖尿病的发生率较低（19.8%对32.6%,P = 0.049），以及a组白细胞减少症低于2000/mm3的发生率较高（28.6%对9.8%,P = 0.001）和中性粒细胞减少症（26.7%对7.9%,P < 0.001）。在新肝移植受者中，强化和单独调整剂量的霉酚酸酯与Tac联合使用，可以在移植后第1天停用CS，具有良好的耐受性和极低的排斥发生率。
Background. We conducted a randomized multicenter open-label trial in de novo liver transplant recipients to assess the feasibility and potential benefit of a corticosteroid (CS)-free regimen coupled with tacrolimus (Tac) and dose-intensifiedmycophenolate mofetil (MMF) further adjusted individually. Methods. Adult liver transplant recipients were randomized on the day of transplantation to a CS-free regimen with Tac and MMF starting at 3 g/d and dose adjusted from day 5 according to mycophenolic acid (MPA) exposure (arm A) or a regimen with CS maintained up to 6 months, Tac and fixed-dose MMF (2 g/d) (arm B). The primary end point was the proportion of patients who experienced treated biopsy-proven acute rejection (BPAR) during the first year posttransplant. Results. One hundred eighty-seven patients were randomized, and 174 comprised the per-protocol population (87 in each arm). The primary objective of noninferiority was met: 7 patients in arm A (8%) and 8 in armB (9%) experienced treated BPAR in the first year. Two patients in arm A (2%) and 5 in arm B (6%) lost their graft, and 12-month patient survival was similar in both arms (90.8% vs 89.8%; P = 0.86). Adverse events were comparable between arms, except for a lower incidence of de novo diabetes (19.8% vs 32.6%, P = 0.049) and a higher incidence of leukopenia less than 2000/mm3 (28.6% vs 9.8%; P = 0.001) and neutropenia (26.7% vs 7.9%; P < 0.001) in arm A. Conclusions. Mycophenolate mofetil at intensified and individually adjusted dose in combination with Tac in de novo liver transplant recipients allows CS discontinuation from day 1 posttransplant with good tolerance and very low rejection incidence.