采用无钙调神经磷酸酶抑制剂、贝拉西普联合依维莫司的免疫抑制方案治疗初发肾移植受者
Treatment of De Novo Renal Transplant Recipients With Calcineurin Inhibitor-free, Belatacept Plus Everolimus-based Immunosuppression.
作者信息
Peddi V Ram, Marder Bradley, Gaite Luis, Oberholzer Jose, Goldberg Ryan, Pearson Thomas, Yang Harold, Allamassey Lisa, Polinsky Martin, Formica Richard N
机构信息
Department of Transplantation, California Pacific Medical Center, San Francisco, CA.
Division of Transplant Research, Colorado Kidney Care, Denver, CO.
出版信息
Transplant Direct. 2023 Jan 6;9(2):e1419. doi: 10.1097/TXD.0000000000001419. eCollection 2023 Feb.
UNLABELLED
Compared with calcineurin inhibitor-based immunosuppression, belatacept (BELA)-based treatment has been associated with better renal function but higher acute rejection rates. This phase 2 study (NCT02137239) compared the antirejection efficacy of BELA plus everolimus (EVL) with tacrolimus (TAC) plus mycophenolate mofetil (MMF), each following lymphocyte-depleting induction and rapid corticosteroid withdrawal.
METHODS
Patients who were de novo renal transplant recipients seropositive for Epstein-Barr virus were randomized to receive BELA+EVL or TAC+MMF maintenance therapy after rabbit antithymocyte globulin induction and up to 7 d of corticosteroids. The primary endpoint was the rate of biopsy-proven acute rejection at month 6.
RESULTS
Because of an unanticipated BELA supply constraint, enrollment was prematurely terminated at 68 patients, of whom 58 were randomized and transplanted (intention-to-treat [ITT] population: n = 26, BELA+EVL; n = 32, TAC+MMF). However, 25 patients received BELA+EVL' and 33 received TAC+MMF (modified ITT population). In the ITT population, the 6-mo biopsy-proven acute rejection rates were 7.7% versus 9.4% in the BELA+EVL versus TAC+MMF group. The corresponding 24-mo biopsy-proven acute rejection rates were 19.2% versus 12.5% in the ITT population and 16.0% versus 15.2% in the mITT population; all events were Banff severity grade ≤IIA and similar between groups. One patient in each group experienced graft loss unrelated to acute rejection. The 24-mo mean unadjusted estimated glomerular filtration rates were 71.8 versus 68.7 mL/min/1.73 m in the BELA+EVL versus TAC+MMF groups. Posttransplant lymphoproliferative disorder was reported for 1 patient in each group. No deaths or unexpected adverse events were observed.
CONCLUSIONS
A steroid-free maintenance regimen of BELA+EVL may be associated with biopsy-proven acute rejection rates comparable to TAC+MMF.
未标注
与基于钙调神经磷酸酶抑制剂的免疫抑制相比，基于贝拉西普（BELA）的治疗与更好的肾功能相关，但急性排斥反应率更高。这项2期研究（NCT02137239）比较了贝拉西普加依维莫司（EVL）与他克莫司（TAC）加霉酚酸酯（MMF）的抗排斥疗效，二者均在淋巴细胞清除诱导和快速停用糖皮质激素后使用。
方法
初发肾移植受者且爱泼斯坦 - 巴尔病毒血清学阳性的患者，在接受兔抗胸腺细胞球蛋白诱导和最多7天的糖皮质激素治疗后，随机接受贝拉西普+依维莫司或他克莫司+霉酚酸酯维持治疗。主要终点是6个月时活检证实的急性排斥反应发生率。
结果
由于贝拉西普供应出现意外限制，研究在纳入68例患者后提前终止，其中58例被随机分组并进行移植（意向性分析[ITT]人群：贝拉西普+依维莫司组n = 26；他克莫司+霉酚酸酯组n = 32）。然而，25例患者接受了贝拉西普+依维莫司治疗，33例接受了他克莫司+霉酚酸酯治疗（改良ITT人群）。在ITT人群中，贝拉西普+依维莫司组与他克莫司+霉酚酸酯组6个月时活检证实的急性排斥反应率分别为7.7%和9.4%。ITT人群中相应的24个月活检证实的急性排斥反应率分别为19.2%和12.5%；改良ITT人群中分别为16.0%和15.2%；所有事件的班夫严重程度分级均≤IIA，且两组间相似。每组各有1例患者出现与急性排斥反应无关的移植物丢失。贝拉西普+依维莫司组与他克莫司+霉酚酸酯组24个月时未调整的平均估计肾小球滤过率分别为71.8和68.7 mL/min/1.73 m²。每组各有1例患者报告发生移植后淋巴细胞增生性疾病。未观察到死亡或意外不良事件。
结论
贝拉西普+依维莫司的无糖皮质激素维持方案可能与活检证实急性排斥反应率与他克莫司+霉酚酸酯相当。
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