Liu Jen-Wei, Lin Shen-Hua, Wang Lin-Chien, Chiu Hsiao-Yean, Lee Jen-Ai
Department of Pharmacy, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan.
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
JAMA Netw Open. 2021 Aug 2;4(8):e2119151. doi: 10.1001/jamanetworkopen.2021.19151.
Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events.
To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children.
Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020).
Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo.
Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020.
The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).
A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41).
In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.
在流感病毒与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）共同在社区传播期间，对于患有流感样疾病的患者，推荐进行抗病毒治疗；然而，关于哪种治疗方法能带来最佳疗效且不良事件最少，仍存在疑问。
比较神经氨酸酶抑制剂和核酸内切酶抑制剂在健康成人和儿童中治疗季节性流感的疗效和安全性。
检索了Medline、Embase和Cochrane临床试验注册库，检索时间从建库至2020年1月（最后一次检索于2020年10月更新）。
纳入的研究为随机临床试验，研究对象为所有年龄段的流感患者，这些患者接受了神经氨酸酶抑制剂（即奥司他韦、帕拉米韦、扎那米韦或拉尼米韦）或核酸内切酶抑制剂（即巴洛沙韦）治疗，并与其他活性药物或安慰剂进行比较。
两名研究人员识别研究并独立提取数据。进行了频率学派网络荟萃分析；使用P值概率对药物进行相对排名。使用推荐分级、评估、制定与评价标准评估证据质量。数据于2020年10月进行分析。
流感症状缓解时间（TTAS）、流感并发症以及不良事件（总不良事件、恶心和呕吐）。
共识别出26项研究了高剂量或低剂量抗病毒药物的试验；这些试验包括11897名参与者，其中6294名（52.9%）为男性，平均（标准差）年龄为32.5（16.9）岁。在所有与安慰剂比较疗效结局的治疗中，高质量证据表明扎那米韦与最短的TTAS相关（风险比，0.67；95%置信区间，0.58 - 0.77），而基于中等质量证据，巴洛沙韦与流感相关并发症的最低风险相关（风险比[RR]，0.51；95%置信区间，0.32 - 0.80）。在安全性结局方面，基于中等质量证据，与安慰剂相比，巴洛沙韦与总不良事件的最低风险相关（RR，0.84；95%置信区间，0.74 - 0.96）。在所有比较中，除75毫克奥司他韦与恶心（RR，1.82；95%置信区间，1.38 - 2.41）和呕吐（RR，1.88；95%置信区间，1.47 - 2.41）的发生率较高相关外，没有强有力的证据表明与恶心或呕吐风险有关联。
在这项系统评价和网络荟萃分析中，评估的所有4种抗病毒药物均与缩短TTAS相关；扎那米韦与最短的TTAS相关，巴洛沙韦与流感相关并发症发生率降低相关。
