美国弗吉尼亚大学卫生系统Frederick G. Hayden团队研究了巴洛沙韦预防家庭接触者患流感的效果。该研究于2020年7月9日发表在《新英格兰医学杂志》上。

巴洛沙韦是一种聚合酶酸性蛋白（PA）核酸内切酶抑制剂，临床上可有效治疗单纯性流感，包括并发症风险较高的门诊患者。尚不清楚巴洛沙韦在家庭环境中暴露后预防的效果。

研究组进行了一项多中心、双盲、随机、安慰剂对照试验，以评估2018-2019年流感季在日本确诊流感患者的家庭接触中，使用巴洛沙韦暴露后预防的效果。研究组共招募了545名流感患者的752位家庭接触者，按1：1随机分组，分别接受单剂量的巴洛沙韦或安慰剂。

545名患者中有95.6%感染了甲型流感病毒，73.6%小于12岁，52.7%接受巴洛沙韦治疗。巴洛沙韦组中有374名，安慰剂组中有375名可参与评估，巴洛沙韦组的临床流感发生率为1.9%，显著低于安慰剂组（13.6%），校正后的风险比为0.14。巴洛沙韦在高风险、小儿和未接种疫苗的参与者亚组中均有效。

不论症状如何，使用巴洛沙韦后，流感感染风险均低于安慰剂组。巴洛沙韦组的不良事件发生率为22.2%，安慰剂组为20.5%，相差不大。巴洛沙韦组中，在10名（2.7%）和5名（1.3%）参与者中分别检测到病毒PA I38T/M或E23K突变 。无法检测到这些突变从接受巴洛沙韦治疗的患者传播至安慰剂组，但不能排除巴洛沙韦组内传播的情况。

总之，单剂量巴洛沙韦可预防流感患者家庭接触者感染流感的风险。

附：英文原文

Title: Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts

Author: 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.

Issue&Volume: 2020-07-08

Abstract: Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza.

DOI: 10.1056/NEJMoa1915341

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1915341