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.).
N Engl J Med. 2020 Jul 23;383(4):309-320. doi: 10.1056/NEJMoa1915341. Epub 2020 Jul 8.
Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear.
We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed.
A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out.
Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.).
巴洛沙韦马波西利（baloxavir marboxil，baloxavir）是一种聚合酶酸性蛋白（PA）内切酶抑制剂，具有治疗包括门诊并发症高危患者在内的单纯性流感的临床疗效。在家庭环境中，巴洛沙韦的暴露后预防效果尚不清楚。
我们开展了一项多中心、双盲、随机、安慰剂对照试验，以评估 2018-2019 年日本流感确诊患者家庭接触者在暴露后应用巴洛沙韦的预防效果。参与者按照 1:1 的比例随机分配，接受单次剂量的巴洛沙韦或安慰剂治疗。主要终点为 10 天内通过逆转录-聚合酶链反应（RT-PCR）检测确认的临床流感。评估了与降低敏感性相关的巴洛沙韦选择的 PA 取代的发生情况。
共有 545 例确诊患者的 752 名家庭接触者被随机分配接受巴洛沙韦或安慰剂治疗。在确诊患者中，95.6%的患者感染了甲型流感病毒，73.6%的患者年龄小于 12 岁，52.7%的患者接受了巴洛沙韦治疗。在可评估的参与者中（巴洛沙韦组 374 例，安慰剂组 375 例），巴洛沙韦组临床流感的发生率明显低于安慰剂组（1.9%比 13.6%）（调整后的风险比，0.14；95%置信区间[CI]，0.06 至 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均有效。无论症状如何，与安慰剂相比，感染流感的风险均较低（调整后的风险比，0.43；95%CI，0.32 至 0.58）。两组不良反应发生率相似（巴洛沙韦组 22.2%，安慰剂组 20.5%）。在巴洛沙韦组中，分别有 10（2.7%）和 5（1.3%）名参与者检测到病毒 PA 取代 I38T/M 或 E23K。未检测到这些变异株从接受巴洛沙韦治疗的指数患者传播给安慰剂组的参与者；然而，不能排除这些变异株从接受巴洛沙韦治疗的指数患者传播给巴洛沙韦组的参与者的情况。
单次剂量的巴洛沙韦对预防流感确诊患者家庭接触者感染流感具有显著的暴露后预防效果。（由盐野义公司资助；日本主要登记处网络编号，JapicCTI-184180。）
