The Second Hospital of HeBei Medical University, Shijiazhuang, China.
J Med Virol. 2022 Jul;94(7):3270-3302. doi: 10.1002/jmv.27729. Epub 2022 Apr 4.
To conduct network meta-analysis (NMA) of clinical efficacy and safety of single-dose antiviral drugs, grouped by dosage, in treatment of influenza. Systematic retrievals were conducted in databases, including Pubmed, Embase, Web of Science, the Cochrane Register of Clinical Trials and from the website ClinicalTrials.gov, for clinical trials recorded between the interception of the databases and March 31, 2021. Randomized controlled trials (RCTs) of influenza treatment in which single-dose antiviral drugs were administered were selected according to preset inclusion and exclusion criteria by two researchers who screened the literature independently from each other. The quality of the included studies was assessed using the Cochrane bias risk assessment tool. Software such as Stata 16.0 and Review Manager 5.3 was adopted for statistical analysis. Pairwise meta-analysis and NMA were carried out under the random-effects model. For both binary and continuous variables, odds ratio (OR), mean difference (MD) and their 95% confidence intervals (CI) were used to rank treatment efficiencies and analyze the differences. A total of 12 RCTs involving 7296 participants were included in the analysis. According to the NMA results, peramivir 300 mg (MD = -17.68, 95% CI: [-34.05, -1.32]), peramivir 600 mg (MD = -16.15, 95% CI: [-29.35, -2.95]), baloxavir (MD = -14.67, 95% CI: [-26.75, -2.58]) and laninamivir 40 mg (MD = -12.42, 95% CI: [-22.53, -2.31]) remarkably outperformed laninamivir 20 mg in time to alleviation of symptoms (TTAS). However, no intervention statistically outperform others in antipyretic time, virus titer variations against the baseline 24 and 48 h after medication and adverse events (AEs). The efficacy rankings were: peramivir 300 mg (the surface under the cumulative ranking curve [SUCRA] = 80.3%) > peramivir 600 mg (SUCRA = 76.2%) > baloxavir (SUCRA = 68.4%) > laninamivir 40 mg (SUCRA = 55.0%) > laninamivir 20 mg (SUCRA = 16.6%) for TTAS; baloxavir (SUCRA = 76.3%) > peramivir 600 mg (SUCRA = 67.8%) > laninamivir 40 mg (SUCRA = 47.2%) > laninamivir 20 mg (SUCRA = 40.0%) for antipyretic time; baloxavir (SUCRA = 96.7%) > peramivir 300 mg (SUCRA = 64.5%) ≈ peramivir 600 mg (SUCRA = 63.2%), baloxavir (SUCRA = 93.2%) > peramivir 600 mg (SUCRA = 64.0%) ≈ peramivir 300 mg (SUCRA = 55.0%), for virus titer variations against the baseline 24 and 48 h after medication, respectively; and baloxavir (SUCRA = 83.4%) > peramivir 300 mg (SUCRA = 71.4%) > laninamivir 20 mg (SUCRA = 62.4%) > peramivir 600 mg (SUCRA = 56.2%) > laninamivir 40 mg (SUCRA = 36.8%) for adverse events. Among the single-dose anti-influenza virus drugs compared, peramivir is superior to baloxavir and laninamivir in TTAS, whereas baloxavir has the best efficacy in antipyretic time, virus titer variations against the baseline 24 and 48 h after medication and AEs. This study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO), with a registration number of CRD42021238220.
为了对流感单次剂量抗病毒药物的临床疗效和安全性进行网络荟萃分析（NMA），我们按照剂量分组进行检索。系统检索了 Pubmed、Embase、Web of Science、Cochrane 临床试验注册中心和 ClinicalTrials.gov 网站，检索时间截至 2021 年 3 月 31 日。我们按照预先设定的纳入和排除标准，选择了接受单次剂量抗病毒药物治疗的流感治疗的随机对照试验（RCT）。两名研究人员独立筛选文献，评估纳入研究的质量采用 Cochrane 偏倚风险评估工具。采用 Stata 16.0 和 Review Manager 5.3 软件进行统计分析。在随机效应模型下进行了两两荟萃分析和 NMA。对于二分类和连续性变量，采用比值比（OR）、均数差（MD）及其 95%置信区间（CI）来对治疗效果进行排序，并分析差异。共有 12 项 RCT 纳入了 7296 名参与者。根据 NMA 结果，帕拉米韦 300mg（MD=-17.68，95%CI：[-34.05，-1.32]）、帕拉米韦 600mg（MD=-16.15，95%CI：[-29.35，-2.95]）、巴洛沙韦（MD=-14.67，95%CI：[-26.75，-2.58]）和拉尼米韦 40mg（MD=-12.42，95%CI：[-22.53，-2.31]）在症状缓解时间（TTAS）方面明显优于拉尼米韦 20mg。然而，在退热时间、用药后 24 和 48 小时病毒滴度变化以及不良事件（AE）方面，没有干预措施在统计学上优于其他药物。疗效排序为：帕拉米韦 300mg（累积排序概率曲线下面积[SUCRA]为 80.3%）＞帕拉米韦 600mg（SUCRA 为 76.2%）＞巴洛沙韦（SUCRA 为 68.4%）＞拉尼米韦 40mg（SUCRA 为 55.0%）＞拉尼米韦 20mg（SUCRA 为 16.6%）；巴洛沙韦（SUCRA 为 76.3%）＞帕拉米韦 600mg（SUCRA 为 67.8%）＞拉尼米韦 40mg（SUCRA 为 47.2%）＞拉尼米韦 20mg（SUCRA 为 40.0%）；巴洛沙韦（SUCRA 为 96.7%）＞帕拉米韦 300mg（SUCRA 为 64.5%）≈帕拉米韦 600mg（SUCRA 为 63.2%），巴洛沙韦（SUCRA 为 93.2%）＞帕拉米韦 600mg（SUCRA 为 64.0%）≈帕拉米韦 300mg（SUCRA 为 55.0%），用药后 24 和 48 小时病毒滴度变化；巴洛沙韦（SUCRA 为 83.4%）＞帕拉米韦 300mg（SUCRA 为 71.4%）＞拉尼米韦 20mg（SUCRA 为 62.4%）＞帕拉米韦 600mg（SUCRA 为 56.2%）＞拉尼米韦 40mg（SUCRA 为 36.8%），用于不良事件。在比较的单次剂量抗流感病毒药物中，帕拉米韦在 TTAS 方面优于巴洛沙韦和拉尼米韦，而巴洛沙韦在退热时间、用药后 24 和 48 小时病毒滴度变化以及不良事件方面的疗效最佳。本研究已在国际前瞻性系统评价注册中心（PROSPERO）注册，注册号为 CRD42021238220。
