Huber Monika, Kemmner Stephan, Renders Lutz, Heemann Uwe
Department of Nephrology, Technical University of Munich, Ismaninger Street 22, Munich 81675, Germany.
Nephrol Dial Transplant. 2016 Dec;31(12):1995-2002. doi: 10.1093/ndt/gfw226. Epub 2016 Jun 10.
Belatacept was developed to minimize cardiovascular risk and nephrotoxicity associated with calcineurin inhibitor (CNI)-based immunosuppression. Recently, 7-year data from the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT), a phase III study comparing belatacept with cyclosporine, have been published. While during the first year of belatacept the risk of acute rejection episodes was elevated, this seemingly had marginal consequences for long-term graft survival and function as well as patient survival.For patients at a low-immunological risk, this drug seems to be a safe and effective alternative to CNI-based immunosuppression. Whether the higher rates of acute rejection episodes in the first year outweigh the gain in long-term graft function is still debated. In particular, the lower incidence of donor-specific antibodies indicates that belatacept should not be considered as lower intensity immunosuppression over the long term.Therefore, should belatacept be the centrepiece of immunosuppression for renal patients?All randomized trials so far have focussed on patients at a low immunological risk. Furthermore, cyclosporine A (CsA), the comparator of belatacept in BENEFIT and the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT), is not the CNI of choice in modern transplantation. Furthermore, while at Year 7 the rate of cancer and infections was comparable with the CsA group, long-term data are missing on safety issues for a large number of patients. Thus, currently belatacept may be the drug of choice for a select group of patients, but not for everyone.This review highlights the benefits and uncertainties of the use of belatacept in kidney transplantation.
贝拉西普的研发旨在将与钙调神经磷酸酶抑制剂(CNI)为基础的免疫抑制相关的心血管风险和肾毒性降至最低。最近,一项将贝拉西普与环孢素进行比较的III期研究——贝拉西普作为一线免疫抑制的肾保护和疗效评估试验(BENEFIT)的7年数据已发表。虽然在使用贝拉西普的第一年急性排斥反应的风险有所升高,但这似乎对长期移植肾存活和功能以及患者存活影响甚微。对于免疫风险较低的患者,这种药物似乎是基于CNI的免疫抑制的一种安全有效的替代方案。第一年较高的急性排斥反应发生率是否超过长期移植肾功能的获益仍存在争议。特别是,供体特异性抗体的较低发生率表明,从长期来看,不应将贝拉西普视为强度较低的免疫抑制药物。那么,贝拉西普是否应该成为肾病患者免疫抑制的核心药物呢?到目前为止,所有随机试验都集中在免疫风险较低的患者身上。此外,环孢素A(CsA)是BENEFIT试验以及贝拉西普作为一线免疫抑制的肾保护和疗效评估试验——扩展标准供体(BENEFIT-EXT)中贝拉西普的对照药物,但它并非现代移植中首选的CNI。此外,虽然在第7年时癌症和感染发生率与环孢素A组相当,但大量患者在安全问题方面的长期数据仍缺失。因此,目前贝拉西普可能是特定患者群体的首选药物,但并非适用于所有人。本综述强调了在肾移植中使用贝拉西普的益处和不确定性。