Kobashigawa J, Ross H, Bara C, Delgado J F, Dengler T, Lehmkuhl H B, Wang S-S, Dong G, Witte S, Junge G, Potena L
Cedars-Sinai Heart Institute, Los Angeles, California, USA.
Transpl Infect Dis. 2013 Apr;15(2):150-62. doi: 10.1111/tid.12007. Epub 2012 Sep 26.
Cytomegalovirus (CMV) causes several complications following cardiac transplantation including cardiac allograft vasculopathy. Previous studies suggested that immunosuppressive treatment based on everolimus might reduce CMV infection. Aiming to better characterize the action of everolimus on CMV and its interplay with patient/recipient serology and anti-CMV prophylaxis, we analyzed data from 3 large randomized studies comparing various everolimus regimens with azathioprine (AZA)- and mycophenolate mofetil (MMF)-based regimens.
CMV data were analyzed from 1009 patients in 3 trials of de novo cardiac transplant recipients who were randomized to everolimus 1.5 mg/day, everolimus 3 mg/day, or AZA 1-3 mg/kg/day, plus standard-dose (SD) cyclosporine (CsA; study B253, n = 634); everolimus 1.5 mg/day plus SD- or reduced-dose (RD)-CsA (study A2403, n = 199); and everolimus 1.5 mg/day plus RD-CsA or MMF plus SD-CsA (study A2411, n = 176).
In study B253, patients allocated to everolimus experienced almost a 70% reduction in odds of experiencing CMV infection compared with AZA (P < 0.001). In study A2403, CMV infection was low in both everolimus arms, irrespective of CsA dosing, and in study A2411, patients allocated to everolimus experienced an 80% reduction in odds of experiencing CMV infection, compared with MMF (P < 0.001). CMV syndrome/disease was rare and less frequent in everolimus-treated patients. Subgroup analyses showed that the benefit everolimus provides, in terms of CMV events, is retained in CMV-naïve recipients and is independent of anti-CMV prophylaxis or preemptive approaches.
Everolimus is associated with a lower incidence of CMV infection compared with AZA and MMF, which combined with its immunosuppressive efficacy and antiproliferative effects may positively impact long-term outcomes.
巨细胞病毒（CMV）可导致心脏移植术后出现多种并发症，包括心脏移植血管病变。既往研究表明，基于依维莫司的免疫抑制治疗可能会降低CMV感染。为了更好地描述依维莫司对CMV的作用及其与患者/受者血清学和抗CMV预防措施的相互作用，我们分析了3项大型随机研究的数据，这些研究比较了各种依维莫司方案与基于硫唑嘌呤（AZA）和霉酚酸酯（MMF）的方案。
对3项初次心脏移植受者试验中的1009例患者的CMV数据进行分析，这些患者被随机分配至依维莫司1.5mg/天、依维莫司3mg/天或AZA 1 - 3mg/kg/天，加标准剂量（SD）环孢素（CsA；研究B253，n = 634）；依维莫司1.5mg/天加SD - 或减量（RD） - CsA（研究A2403，n = 199）；以及依维莫司1.5mg/天加RD - CsA或MMF加SD - CsA（研究A2411，n = 176）。
在研究B253中，与AZA组相比，分配至依维莫司组的患者发生CMV感染的几率降低了近70%（P < 0.001）。在研究A2403中，两个依维莫司组的CMV感染率均较低，与CsA剂量无关；在研究A2411中，与MMF组相比，分配至依维莫司组的患者发生CMV感染的几率降低了80%（P < 0.001）。CMV综合征/疾病罕见，且在接受依维莫司治疗的患者中发生率较低。亚组分析表明，依维莫司在CMV事件方面的益处，在未感染CMV的受者中依然存在，且与抗CMV预防措施或抢先治疗方法无关。
与AZA和MMF相比，依维莫司与较低的CMV感染发生率相关，这与其免疫抑制疗效和抗增殖作用相结合，可能对长期预后产生积极影响。
