University of Barcelona, IDIBELL, Barcelona, Spain.
Instituto de Nefrologia, Buenos Aires, Argentina.
Am J Kidney Dis. 2017 May;69(5):587-594. doi: 10.1053/j.ajkd.2016.09.021. Epub 2016 Nov 23.
In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss.
36-month follow-up of the intention-to-treat population.
SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m).
At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89).
Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed.
Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy.
Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73m per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P=0.9).
Exploratory post hoc analysis with a small sample size.
Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.
在一项 2 期研究中，与继续接受钙调磷酸酶抑制剂（CNI）治疗的患者相比，低免疫风险的肾移植受者在转换为巴利昔单抗后 12 个月时肾功能得到改善，急性排斥反应发生率低，无移植丢失。
意向治疗人群的 36 个月随访。
具有稳定移植功能（估计肾小球滤过率[eGFR]，35-75mL/min/1.73m）的 CNI 治疗成年肾移植受者。
移植后 6-36 个月，患者随机分配至接受巴利昔单抗为基础的免疫抑制治疗（n=84）或继续 CNI 为基础的治疗（n=89）。
安全性是主要结局。还评估了 eGFR、急性排斥反应、移植丢失和死亡。
安全性的治疗暴露调整发生率，eGFR 的重复测量模型，疗效的 Kaplan-Meier 分析。
巴利昔单抗治疗组 33 例（39%）和 CNI 组 36 例（40%）患者发生严重不良事件。严重感染（巴利昔单抗与 CNI，每 100 人年 10.21 比 9.31）和恶性肿瘤（每 100 人年 3.01 比 3.41）的治疗暴露调整发生率相似。巴利昔单抗组较 CNI 组有更多的任何级别病毒感染（每 100 人年 14.60 比 11.00）。无移植后淋巴增殖性疾病报告。与 CNI 相比，巴利昔单抗治疗组 eGFR 估计平均增益显著更大（每年 1.90 比 0.07mL/min/1.73m；时间与治疗交互作用的 P 值为 0.01）。巴利昔单抗的急性排斥反应概率与 CNI 相比无显著差异（8.38%比 3.60%；HR，2.50[95%CI，0.65-9.65；P=0.2]）。与 CNI 相比，巴利昔单抗组死亡或移植丢失的时间 HR 为 1.00（95%CI，0.14-7.07；P=0.9）。
小样本量的探索性事后分析。
将患者从 CNI 转换为巴利昔单抗可能是一种安全的免疫抑制方法，正在一项正在进行的 3b 期试验中进一步探索。
