Leidos Biomedical Research, Frederick, MD, USA.
Department of Internal Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lancet Respir Med. 2017 Jun;5(6):500-511. doi: 10.1016/S2213-2600(17)30174-1. Epub 2017 May 15.
Influenza causes substantial morbidity and mortality despite available treatments. Anecdotal reports suggest that plasma with high antibody titres to influenza might be of benefit in the treatment of severe influenza.
In this randomised, open-label, multicentre, phase 2 trial, 29 academic medical centres in the USA assessed the safety and efficacy of anti-influenza plasma with haemagglutination inhibition antibody titres of 1:80 or more to the infecting strain. Hospitalised children and adults (including pregnant women) with severe influenza A or B (defined as the presence of hypoxia or tachypnoea) were randomly assigned to receive either two units (or paediatric equivalent) of anti-influenza plasma plus standard care, versus standard care alone, and were followed up for 28 days. The primary endpoint was time to normalisation of patients' respiratory status (respiratory rate of ≤20 breaths per min for adults or age-defined thresholds of 20-38 breaths per min for children) and a room air oxygen saturation of 93% or more. This study is registered with ClinicalTrials.gov, number NCT01052480.
Between Jan 13, 2011, and March 2, 2015, 113 participants were screened for eligibility and 98 were randomly assigned from 20 out of 29 participating sites. Of the participants with confirmed influenza (by PCR), 28 (67%) of 42 in the plasma plus standard care group normalised their respiratory status by day 28 compared with 24 (53%) of 45 participants on standard care alone (p=0·069). The hazard ratio (HR) comparing plasma plus standard care with standard care alone was 1·71 (95% CI 0·96-3·06). Six participants died, one (2%) from the plasma plus standard care group and five (10%) from the standard care group (HR 0·19 [95% CI 0·02-1·65], p=0·093). Participants in the plasma plus standard care group had non-significant reductions in days in hospital (median 6 days [IQR 4-16] vs 11 days [5-25], p=0·13) and days on mechanical ventilation (median 0 days [IQR 0-6] vs 3 days [0-14], p=0·14). Fewer plasma plus standard care participants had serious adverse events compared with standard care alone recipients (nine [20%] of 46 vs 20 [38%] of 52, p=0·041), the most frequent of which were acute respiratory distress syndrome (one [2%] vs two [4%] patients) and stroke (one [2%] vs two [4%] patients).
Although there was no significant effect of plasma treatment on the primary endpoint, the treatment seemed safe and well tolerated. A phase 3 randomised trial is now underway to further assess this intervention.
National Institute of Allergy and Infectious Diseases, US National Institutes of Health.
尽管有可用的治疗方法，但流感仍会导致大量发病和死亡。一些传闻报告表明，具有高滴度抗流感抗体的血浆可能对治疗严重流感有益。
在这项随机、开放标签、多中心的 2 期临床试验中，美国 29 家学术医疗中心评估了血凝抑制抗体滴度为 1:80 或更高的抗流感血浆在严重甲型或乙型流感（定义为存在缺氧或呼吸急促）患者中的安全性和疗效。将住院的儿童和成人（包括孕妇）随机分配接受两单位（或儿科等效物）抗流感血浆加标准治疗，或仅接受标准治疗，并随访 28 天。主要终点是患者呼吸状态正常化的时间（成人呼吸频率≤20 次/分钟或儿童为年龄定义的 20-38 次/分钟）和 93%或更高的室内空气氧饱和度。这项研究在 ClinicalTrials.gov 注册，编号为 NCT01052480。
2011 年 1 月 13 日至 2015 年 3 月 2 日期间，有 113 名患者接受了筛选以确定其是否符合入选条件，其中 98 名患者来自 29 个参与中心中的 20 个中心。在确诊为流感（通过 PCR）的参与者中，与仅接受标准治疗的 45 名参与者中的 24 名（53%）相比，血浆加标准治疗组有 28 名（67%）在第 28 天呼吸状态正常化（p=0.069）。与标准治疗相比，血浆加标准治疗的危险比（HR）为 1.71（95%CI 0.96-3.06）。有 6 名参与者死亡，1 名（2%）来自血浆加标准治疗组，5 名（10%）来自标准治疗组（HR 0.19[95%CI 0.02-1.65]，p=0.093）。与标准治疗相比，接受血浆加标准治疗的患者住院时间（中位数 6 天[IQR 4-16] 与 11 天[5-25]，p=0.13）和机械通气时间（中位数 0 天[IQR 0-6] 与 3 天[0-14]，p=0.14）有非显著减少。与标准治疗相比，接受血浆加标准治疗的患者发生严重不良事件的比例较低（46 名患者中有 9 名[20%]与 52 名患者中有 20 名[38%]，p=0.041），最常见的是急性呼吸窘迫综合征（1 名[2%]与 2 名[4%]患者）和中风（1 名[2%]与 2 名[4%]患者）。
尽管血浆治疗对主要终点没有显著影响，但该治疗似乎是安全且耐受良好的。目前正在进行一项 3 期随机试验，以进一步评估这种干预措施。
美国国立过敏和传染病研究所，美国国立卫生研究院。
