a Service de Néphrologie, Hémodialyse , Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes , Grenoble , France.
b Université Grenoble Alpes , Grenoble , France.
Expert Rev Clin Immunol. 2019 Apr;15(4):359-367. doi: 10.1080/1744666X.2019.1574570. Epub 2019 Feb 7.
Since the approval of belatacept in 2011 for use in the setting of de novo kidney transplantation, this CD80/86 - CD28 co-stimulation blocker has been shown to be a valuable treatment option for maintenance immunosuppression. Areas covered: In this setting, belatacept has been associated with superior glomerular filtration rate as compared to calcineurin inhibitor-based treatments because of the absence of nephrotoxicity. Additionally, belatacept avoids the cardiovascular side effects (e.g. hypertension and dyslipidemia) caused by a CNI-based-regimen. Nevertheless, belatacept-treated recipients have a higher rate of acute rejections and a higher risk of lymphoproliferative disorders. Expert opinion: Data suggest a benefit from early conversion vs. late conversion of belatacept in a conversion setting following CNI-related toxicity. Randomized studies are currently comparing belatacept to tacrolimus, instead of cyclosporine, as was done in the Belatacept Evaluation of Nephroprotection and Efficacy as a First-line Immunosuppression Trial (BENEFIT). The benefits and limitations of belatacept seem to be the same when tacrolimus is used instead of cyclosporine. Finally, we also report in this review on the immunological data available so far that explain belatacept's limitations and the higher rate of acute rejection. The goal is to find the optimal immunosuppressive strategy to improve efficacy and safety at post-transplantation.
自 2011 年贝利尤单抗获批用于治疗初发性肾脏移植以来,这种 CD80/86-CD28 共刺激阻断剂已被证明是维持免疫抑制的一种有价值的治疗选择。
在这种情况下,与基于钙调磷酸酶抑制剂的治疗相比,贝利尤单抗可带来更高的肾小球滤过率,因为它没有肾毒性。此外,贝利尤单抗避免了基于 CNI 方案引起的心血管副作用(如高血压和血脂异常)。然而,接受贝利尤单抗治疗的受者急性排斥反应发生率更高,淋巴增殖性疾病风险更高。
数据表明,在 CNI 相关毒性的转换背景下,与迟转换相比,早期转换可能有获益。目前,随机研究正在比较贝利尤单抗与他克莫司,而不是环孢素,就像在贝利尤单抗评估肾保护和作为一线免疫抑制治疗的疗效试验(BENEFIT)中那样。当使用他克莫司而不是环孢素时,贝利尤单抗的益处和局限性似乎相同。最后,我们还在这篇综述中报告了迄今为止可用的免疫数据,这些数据解释了贝利尤单抗的局限性和更高的急性排斥反应发生率。目标是找到最佳的免疫抑制策略,以提高移植后的疗效和安全性。