Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis.
Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis.
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DOI：
10.1136/bmj.b5106
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发表时间：
2009-12-08
期刊：
影响因子：
--
通讯作者：
Del Mar C
中科院分区：
文献类型：
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作者：
Jefferson T;Jones M;Doshi P;Del Mar C
目的更新2005年Cochrane的综述，评估神经氨酸酶抑制剂在预防或改善健康成人流感症状、流感传播和流感并发症方面的效果，并估计不良反应的频率。检索策略对Cochrane对照试验中央登记册(Cochrane图书馆，2009年第2期)进行最新检索，其中包含急性呼吸道感染小组的专门登记册Medline(1950-2009年8月)、Embase(1980-2009年8月)以及上市后药物警戒数据和比较安全队列。选择标准神经氨酸酶抑制剂在暴露于自然发生流感的健康成年人中的随机安慰剂对照研究。主要观察指标：症状持续时间和发生率；下呼吸道感染或其代用品的发生率；以及不良事件。数据提取两位评价者应用纳入标准，评估试验质量，并提取数据。数据分析比较被组织成预防、治疗和不良事件，并按结果和剂量进一步细分。结果共纳入20项试验，其中预防试验4项，治疗试验12项，暴露后预防试验4项。在预防方面，神经氨酸酶抑制剂对流感样疾病或无症状流感没有效果。口服奥司他韦每日75 mg对实验室确诊的有症状流感的有效率为61%(风险比0.39，95%可信区间0.18~0.85)，每日150 mg口服奥司他韦的有效率为73%(0.27，0.11~0.67)。吸入扎那米韦10 mg/d有效率为62%(0.38，0.17~0.85)。在两个家庭试验中，奥司他韦用于暴露后预防的有效率分别为58%(95%可信区间15%至79%)和84%(49%至95%)。扎那米韦的表现与此类似。缓解流感样疾病症状所需时间的危险比有利于治疗：奥司他韦1.20(95%可信区间1.06~1.35)，扎那米韦1.24(1.13~1.36)。8项未发表的关于并发症的研究不符合条件，因此被排除在外。其余证据表明，奥司他韦不能减少与流感相关的下呼吸道并发症(风险比0.55，95%可信区间0.22至1.35)。从试验证据看，奥司他韦可引起恶心(优势比1.79，95%可信区间1.10至2.93)。来自药物警戒的更罕见的不良事件的证据质量较差或可能被漏报。结论神经氨酸酶抑制剂对其他健康成人的流感症状有一定的疗效。这些药物对实验室确认的流感暴露后有效，但这是流感样疾病的一小部分，因此神经氨酸酶抑制剂对这一结果无效。神经氨酸酶抑制剂可能被认为是减轻季节性流感症状的可选药物。良好数据的缺乏破坏了先前关于奥司他韦预防流感并发症的研究结果。需要独立的随机试验来解决这些不确定性。
Objectives To update a 2005 Cochrane review that assessed the effects of neuraminidase inhibitors in preventing or ameliorating the symptoms of influenza, the transmission of influenza, and complications from influenza in healthy adults, and to estimate the frequency of adverse effects. Search strategy An updated search of the Cochrane central register of controlled trials (Cochrane Library 2009, issue 2), which contains the Acute Respiratory Infections Group’s specialised register, Medline (1950-Aug 2009), Embase (1980-Aug 2009), and post-marketing pharmacovigilance data and comparative safety cohorts. Selection criteria Randomised placebo controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza. Main outcome measures Duration and incidence of symptoms; incidence of lower respiratory tract infections, or their proxies; and adverse events. Data extraction Two reviewers applied inclusion criteria, assessed trial quality, and extracted data. Data analysis Comparisons were structured into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose. Results 20 trials were included: four on prophylaxis, 12 on treatment, and four on postexposure prophylaxis. For prophylaxis, neuraminidase inhibitors had no effect against influenza-like illness or asymptomatic influenza. The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily and 73% (0.27, 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily was 62% efficacious (0.38, 0.17 to 0.85). Oseltamivir for postexposure prophylaxis had an efficacy of 58% (95% confidence interval 15% to 79%) and 84% (49% to 95%) in two trials of households. Zanamivir performed similarly. The hazard ratios for time to alleviation of influenza-like illness symptoms were in favour of treatment: 1.20 (95% confidence interval 1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Eight unpublished studies on complications were ineligible and therefore excluded. The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35). From trial evidence, oseltamivir induced nausea (odds ratio 1.79, 95% confidence interval 1.10 to 2.93). Evidence of rarer adverse events from pharmacovigilance was of poor quality or possibly under-reported. Conclusion Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed.