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巴洛沙韦酯对流感指示病例家庭接触者的流感预防效果
Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts


Hideyuki Ikematsu ... 呼吸系统疾病 • 2020.07.23
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• 流感的诊断、治疗和化学预防 • 年纪大、病情重的流感样疾病患者可能从奥司他韦治疗中获益最大

摘要


背景

巴洛沙韦酯(巴洛沙韦)(baloxavir marboxil [baloxavir])是一种聚合酶酸性蛋白(PA)内切核酸酶抑制剂,在治疗无并发症的流感方面具有临床疗效(包括在并发症风险增加的门诊患者中)。巴洛沙韦在家庭环境中的暴露后预防效果尚不明确。

 

方法

我们开展了一项多中心、双盲、随机、安慰剂对照试验,目的是评估在日本2018—2019流感季,在确诊流感的指示病例的家庭接触者中,巴洛沙韦的暴露后预防效果。我们以1:1的比例将参与者分组,两组分别接受巴洛沙韦或安慰剂单剂给药。主要终点是在10日期间患经过反转录聚合酶链反应确认的临床流感。我们还评估了巴洛沙韦选择出的,与药敏性降低相关的PA置换的发生情况。

 

结果

我们将545个指示病例的总共752名家庭接触者随机分组,两组分别接受巴洛沙韦或安慰剂给药。指示病例中有95.6%感染了甲型流感病毒,73.6%小于12岁,52.7%接受了巴洛沙韦治疗。在可以评估的参与者(巴洛沙韦组374例和安慰剂组375例)中,巴洛沙韦组患临床流感的百分比显著低于安慰剂组(1.9% vs. 13.6%)(校正风险比,0.14;95%置信区间[CI],0.06~0.30;P<0.001)。巴洛沙韦在高危、儿科和未接种疫苗的参与者亚组中有效。巴洛沙韦组的流感感染(不论是否有症状)风险低于安慰剂组(校正风险比,0.43;95% CI,0.32~0.58)。两组的不良事件发生率相似(巴洛沙韦组22.2%和安慰剂组20.5%)。在巴洛沙韦组中,我们分别检测到10例(2.7%)和5例(1.3%)参与者有病毒PA置换I38T/M或E23K。我们未检测到这些变异体从接受巴洛沙韦治疗的指示病例传播给安慰剂组参与者;然而,不能排除上述变异体传播给数例巴洛沙韦组参与者。

 

结论

单剂巴洛沙韦给药在预防流感患者的家庭接触者患流感方面显示出显著的暴露后预防效果(由盐野义制药[Shionogi]资助,在Japan Primary Registries Network注册号为JapicCTI-184180)。





作者信息

Hideyuki Ikematsu, M.D., Frederick G. Hayden, M.D., Keiko Kawaguchi, M.S., Masahiro Kinoshita, M.Pharm., Menno D. de Jong, M.D., Nelson Lee, M.D., Satoru Takashima, M.S., Takeshi Noshi, M.S., Kenji Tsuchiya, M.S., and Takeki Uehara, Ph.D.
From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) — both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.). Address reprint requests to Dr. Hayden at the Division of Infectious Diseases and International Health, P.O. Box 801342, University of Virginia Health System, Charlottesville, VA 22908, or at fgh@virginia.edu.

 

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