比利时鲁汶大学Johan Maertens团队的一项最新研究发现Maribavir可用于治疗巨细胞病毒（CMV）再活化。2019年9月18日，国际知名医学期刊《新英格兰医学杂志》发表了这一成果。

在这项临床2期、开放标签、Maribavir剂量-盲法试验中，研究组招募了接受造血细胞或实体器官移植的患者，这些患者的年龄均超过18岁，CMV再活化。将其随机分配接受Maribavir400、800或1200 mg治疗，每日两次，或接受缬更昔洛韦的标准治疗，所有治疗均不超过12周。

共有156名患者完成治疗，其中Maribavir组117名，缬更昔洛韦组39名。治疗3周后，Maribavir组中有62%的患者血浆中未检测到CMV DNA，缬更昔洛韦组为56%。治疗6周后，该比例在Maribavir组和缬更昔洛韦组中分别为79%和67%，风险比为1.20。在Maribavir不同剂量组中，未检测到CMV DNA的患者所占比例相似。Maribavir 800 mg组中两名未检测到CMV DNA的患者在6周内复发感染，均出现CMV UL97蛋白激酶T409M耐药突变。Maribavir组中严重不良反应或病情恶化的发生率为44%，显著高于缬更昔洛韦组（32%）。Maribavir组胃肠道不良反应发生率较高，缬更昔洛韦组中性粒细胞减少发生率较高。

总之，每次至少服用400 mg Maribavir，每日两次，用于清除接受造血细胞或实体器官移植患者的CMV病毒血症，其疗效不亚于缬更昔洛韦，但胃肠道不良反应发生率较高，尤其是食欲不振，而中性粒细胞减少发生率较低。

据悉，Maribavir是一种具有抗CMV活性的苯并咪唑核苷。其在移植受者预防治疗CMV感染中的安全性和有效性尚不明确。

附：英文原文

Title: Maribavir for Preemptive Treatment of Cytomegalovirus Reactivation

Author: Johan Maertens, Catherine Cordonnier, Peter Jaksch, Xavier Poiré, Marc Uknis, Jingyang Wu, Anna Wijatyk, Faouzi Saliba, Oliver Witzke, Stephen Villano

Issue&Volume: Vol 381 No 12

Abstract:

Background

Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known.

Methods

In a phase 2, open-label, maribavir dose–blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment.

Results

Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available — 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir.

Conclusions

Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events — notably dysgeusia — and a lower incidence of neutropenia were found in the maribavir group.

DOI: 10.1056/NEJMoa1714656

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1714656