Gao Ya, Zhao Yunli, Liu Ming, Luo Shuyue, Chen Yamin, Chen Xiaoyan, Zheng Qingyong, Xu Jianguo, Shen Yanjiao, Zhao Wanyu, Li Zhifan, Huang Sha, Huang Jie, Tian Jinhui, Guyatt Gordon, Hao Qiukui
Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Healthcare Big Data Research Institute, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
JAMA Intern Med. 2025 Mar 1;185(3):293-301. doi: 10.1001/jamainternmed.2024.7193.
The optimal antiviral drug for treatment of nonsevere influenza remains unclear.
To compare effects of antiviral drugs for treating nonsevere influenza.
MEDLINE, Embase, CENTRAL, CINAHL, Global Health, Epistemonikos, and ClinicalTrials.gov were searched from database inception to September 20, 2023.
Randomized clinical trials comparing direct-acting influenza antiviral drugs to placebo, standard care, or another antiviral drug for treating people with nonsevere influenza.
Paired reviewers independently performed data extraction and risk of bias assessment. A frequentist network meta-analysis was performed to summarize the evidence and the certainty of evidence was evaluated using the GRADE approach.
Mortality, admission to hospital, admission to the intensive care unit, duration of hospitalization, time to alleviation of symptoms, emergence of resistance, and adverse events.
Overall, 73 trials with 34 332 participants proved eligible. Compared with standard care or placebo, all antiviral drugs had little or no effect on mortality for low-risk patients and high-risk patients (all high certainty). All antiviral drugs (no data for peramivir and amantadine) had little or no effect on hospital admission for low-risk patients (high certainty). For hospital admission in high-risk patients, oseltamivir (risk difference [RD], -0.4%; 95% CI, -1.0 to 0.4; high certainty) had little or no effect and baloxavir may have reduced risk (RD, -1.6%; 95% CI, -2.0 to 0.4; low certainty); all other drugs may have had little or uncertain effect. For time to alleviation of symptoms, baloxavir probably reduced symptom duration (mean difference [MD], -1.02 days; 95% CI, -1.41 to -0.63; moderate certainty); umifenovir may have reduced symptom duration (MD, -1.10 days; 95% CI, -1.57 to -0.63; low certainty); oseltamivir probably had no important effect (MD, -0.75 days; 95% CI, -0.93 to -0.57; moderate certainty). For adverse events related to treatment, baloxavir (RD, -3.2%; 95% CI, -5.2 to -0.6; high certainty) had few or no adverse events; oseltamivir (RD, 2.8%; 95% CI, 1.2 to 4.8; moderate certainty) probably increased adverse events.
This systematic review and meta-analysis found that baloxavir probably reduced risk of hospital admission for high-risk patients and may reduce time to alleviation of symptoms, without increasing adverse events related to treatment in patients with nonsevere influenza. All other antiviral drugs either probably have little or no effect, or uncertain effects on patient-important outcomes.
治疗非重症流感的最佳抗病毒药物仍不明确。
比较抗病毒药物治疗非重症流感的效果。
检索了MEDLINE、Embase、CENTRAL、CINAHL、Global Health、Epistemonikos和ClinicalTrials.gov数据库，检索时间从建库至2023年9月20日。
比较直接作用的流感抗病毒药物与安慰剂、标准治疗或另一种抗病毒药物治疗非重症流感患者的随机临床试验。
两名评价员独立进行数据提取和偏倚风险评估。采用频率学派网状Meta分析来汇总证据，并使用GRADE方法评估证据的确定性。
死亡率、住院、入住重症监护病房、住院时间、症状缓解时间、耐药性出现情况及不良事件。
总体而言，73项试验共34332名参与者符合纳入标准。与标准治疗或安慰剂相比，所有抗病毒药物对低风险和高风险患者的死亡率几乎没有影响或无影响（均为高确定性）。所有抗病毒药物（帕拉米韦和金刚烷胺无数据）对低风险患者的住院影响很小或无影响（高确定性）。对于高风险患者的住院情况，奥司他韦（风险差值[RD]，-0.4%；95%置信区间，-1.0至0.4；高确定性）影响很小或无影响，巴洛沙韦可能降低了风险（RD，-1.6%；95%置信区间，-2.0至0.4；低确定性）；所有其他药物可能影响很小或效果不确定。对于症状缓解时间，巴洛沙韦可能缩短了症状持续时间（平均差值[MD]，-1.02天；95%置信区间，-1.41至-0.63；中等确定性）；乌米芬韦可能缩短了症状持续时间（MD，-1.10天；95%置信区间，-1.57至-0.63；低确定性）；奥司他韦可能没有重要影响（MD，-0.75天；95%置信区间，-0.93至-0.57；中等确定性）。对于与治疗相关的不良事件，巴洛沙韦（RD，-3.2%；95%置信区间，-5.2至-0.6；高确定性）不良事件很少或没有；奥司他韦（RD，2.8%；95%置信区间，1.2至4.8；中等确定性）可能增加了不良事件。
本系统评价和Meta分析发现，巴洛沙韦可能降低高风险患者的住院风险，并可能缩短症状缓解时间，且不会增加非重症流感患者与治疗相关的不良事件。所有其他抗病毒药物对患者重要结局可能几乎没有影响、无影响或效果不确定。
