End Points for Testing Influenza Antiviral Treatments for Patients at High Risk of Severe and Life-Threatening Disease
End Points for Testing Influenza Antiviral Treatments for Patients at High Risk of Severe and Life-Threatening Disease
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DOI：
10.1086/652498
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发表时间：
2010-06-01
影响因子：
6.4
通讯作者：
Hayden, Frederick G.
中科院分区：
文献类型：
--
作者：
Ison, Michael G.;de Jong, Menno D.;Hayden, Frederick G.
流感感染导致住院患者的大量发病率和死亡率，包括那些免疫功能低下或怀孕的患者。抗病毒治疗可能为这些患者提供相当大的益处，但在这些高危人群中成功进行的研究很少，并且没有专门许可用于治疗这些亚组的药物。流感新型抗病毒药物开发面临的关键挑战之一是确定适当的疗效终点，以便能够快速监管批准用于重症患者的药物，对这些患者的风险-获益评估与无并发症的患者不同。目前所有可用的抗病毒药物都会影响病毒复制，呼吸道病毒滴度与症状和宿主炎症反应的测量结果相关，包括可能导致许多临床症状的细胞因子和趋化因子表达。因此，我们概述了证据，以支持使用的主要病毒学终点的抗病毒药物的研究，涉及患者谁是住院的严重流感或那些谁是严重的和危及生命的疾病的高风险。
Influenza infection results in substantial morbidity and mortality in hospitalized patients, including those who are immuno-compromised or pregnant. Antiviral therapy likely provides considerable benefit to these patients, but few studies have been successfully conducted in these high-risk populations, and no drugs are specifically licensed for treating these subgroups. One of the key challenges facing novel antiviral drug development for influenza is determining the appropriate efficacy end points that would enable rapid regulatory approval for drug use in seriously ill patients, for whom risk-benefit assessments differ from those with uncomplicated illness. All available antiviral drugs currently affect viral replication, and respiratory tract viral titers correlate with both symptoms and measures of host inflammatory responses, including cytokine and chemokine expression that are likely responsible for many of the clinical symptoms. Consequently, we outline the evidence to support the use of primary virological end points in studies of antiviral agents involving patients who are hospitalized with severe influenza or those who are at high risk of severe and life-threatening disease.