Wolf Sebastian, Hoffmann Verena S, Sommer Florian, Schrempf Matthias, Li Mingming, Ryll Martin, Wirth Ulrich, Ilmer Matthias, Werner Jens, Andrassy Joachim
Department of General, Visceral and Transplant Surgery, University Hospital Augsburg, 86156 Augsburg, Germany.
Institute for Medical Information Processing Biometry and Epidemiology (IBE), Ludwig-Maximilian's University, 81377 Munich, Germany.
J Clin Med. 2022 Jul 20;11(14):4216. doi: 10.3390/jcm11144216.
(1) Background: Following renal transplantation, infection with cytomegalovirus (CMV) is a common and feared complication. mTOR-inhibitor (mTOR-I) treatment, either alone or in combination with calcineurininhibitors (CNIs), significantly reduces the CMV incidence after organ transplantation. As of now, there is no information on which mTOR-I, sirolimus (SIR) or everolimus (ERL), has a stronger anti-CMV effect. (2) Methods: The current literature was searched for prospective randomized controlled trials in renal transplantation. There were 1164 trials screened, of which 27 could be included (11,655 pts.). We performed a network meta-analysis to analyze the relative risk of different types of mTOR-I treatment on CMV infection 12 months after transplantation compared to CNI treatment. (3) Results: Four different types of mTOR-I treatment were analyzed in network meta-analyses—SIR mono, ERL mono, SIR with CNI, ERL with CNI. The mTOR-I treatment with the strongest anti-CMV effect compared to a regular CNI treatment was ERL in combination with a CNI (relative risk (RR) 0.27, confidence interval (CI) 0.22−0.32, p < 0.0001). The other mTOR-I therapy groups showed a slightly decreased anti-CMV efficacy (SIR monotherapy (mono): RR 0.35, CI 0.22−0.57, p < 0.001; SIR with CNI: RR 0.43, CI 0.29−0.64, p < 0.0001; ERL mono: RR 0.46, CI 0.22−0.93, p = 0.031). (4) Conclusions: The anti-CMV effect of both mTOR-Is (SRL and ERL) is highly effective, irrespective of the combination with other immunosuppressive drugs. Certain differences with respect to the potency against the CMV could be found between SRL and ERL. Data gained from this analysis seem to support that a combination of ERL and CNI has the most potent anti-CMV efficacy.
（1）背景：肾移植后，巨细胞病毒（CMV）感染是一种常见且令人担忧的并发症。mTOR抑制剂（mTOR-I）单独治疗或与钙调神经磷酸酶抑制剂（CNI）联合治疗，可显著降低器官移植后的CMV感染发生率。目前，尚无关于哪种mTOR-I（西罗莫司（SIR）或依维莫司（ERL））具有更强抗CMV作用的信息。（2）方法：检索当前文献中肾移植的前瞻性随机对照试验。共筛选出1164项试验，其中27项可纳入（11655例患者）。我们进行了网状Meta分析，以分析与CNI治疗相比，不同类型mTOR-I治疗在移植后12个月时对CMV感染的相对风险。（3）结果：在网状Meta分析中分析了四种不同类型的mTOR-I治疗——SIR单药治疗、ERL单药治疗、SIR联合CNI、ERL联合CNI。与常规CNI治疗相比，抗CMV作用最强的mTOR-I治疗是ERL联合CNI（相对风险（RR）0.27，置信区间（CI）0.22 - 0.32，p < 0.0001）。其他mTOR-I治疗组的抗CMV疗效略有下降（SIR单药治疗（单药）：RR 0.35，CI 0.22 - 0.57，p < 0.001；SIR联合CNI：RR 0.43，CI 0.29 - 0.64，p < 0.0001；ERL单药治疗：RR 0.46，CI 0.22 - 0.93，p = 0.031）。（4）结论：两种mTOR-I（SRL和ERL）的抗CMV作用都非常有效，无论是否与其他免疫抑制药物联合使用。在SRL和ERL之间可以发现针对CMV的效力存在某些差异。从该分析中获得的数据似乎支持ERL和CNI联合使用具有最有效的抗CMV疗效。
