From the The Children's Hospital at Westmead.
National Centre for Immunisation Research and Surveillance.
Pediatr Infect Dis J. 2018 Oct;37(10):971-975. doi: 10.1097/INF.0000000000001949.
Comparing postvaccination fever rates in pediatric influenza vaccine clinical trials is difficult due to variability in how fever is reported. The impact of vaccine-related fever and antipyretic use on trivalent influenza vaccine immunogenicity in children is also unclear.
In this pilot study, we used individual-level data provided by GlaxoSmithKline from 3 pediatric clinical trials of GlaxoSmithKline versus comparator trivalent influenza vaccine. We explored a primary study (NCT00764790), the largest trial involving young children (6-35 months, n = 3317), and further explored key findings in the 2 other trials (3-17 years, NCT00980005; 6 months to 17 years, NCT00383123). We analyzed postvaccination fever and antipyretic use, and their association with immunogenicity through use of multivariable regression.
Postvaccination fever data were reanalyzed from the primary study using the Brighton Collaboration standardized definition (vaccine-related fever ≥38°C, measured by any route, reported after each dose). Rates were substantially lower after first (2.7%-3.4%) and second doses (3.3%-4.1%), than those published (6.2%-6.6%; combined dose data, any causality). A pooled immunogenicity analysis combining the 3 studies (n = 5902) revealed children with postvaccination fever had significantly higher adjusted geometric mean titers than those without fever (ratio, 1.21-1.39; P ≤ 0.01). Conversely those with antipyretic use had significantly lower adjusted geometric mean titers (ratio, 0.80-0.87; P < 0.0006), dependent on virus strain.
Varying analyses and reporting methods can result in substantially different reported fever rates in studies. Standardized reporting of fever is needed to facilitate comparison between studies. Fever and antipyretic use may have important associations with influenza vaccine immunogenicity in children and need further prospective investigation.
由于发热报告方式的差异，比较儿科流感疫苗临床试验中的接种后发热率较为困难。疫苗相关发热和退热药物使用对儿童三价流感疫苗免疫原性的影响也不清楚。
在这项试点研究中，我们使用了葛兰素史克公司（GlaxoSmithKline）提供的来自 3 项葛兰素史克公司与对照三价流感疫苗的儿科临床研究的个体水平数据。我们探索了一项主要研究（NCT00764790），该研究涉及年龄最小的儿童（6-35 个月，n = 3317），并进一步探索了另外 2 项试验（3-17 岁，NCT00980005；6 个月至 17 岁，NCT00383123）的关键发现。我们通过使用多变量回归分析，研究了接种后发热和退热药物使用及其与免疫原性的关系。
我们使用 Brighton 合作组织标准化定义（通过任何途径测量的疫苗相关发热≥38°C，在每次剂量后报告）重新分析了主要研究中的接种后发热数据。与已发表数据（联合剂量数据，任何因果关系，6.2%-6.6%）相比，第一剂（2.7%-3.4%）和第二剂（3.3%-4.1%）后的发热率显著更低。结合 3 项研究（n = 5902）的汇总免疫原性分析显示，接种后发热的儿童调整后的几何平均滴度显著高于无发热的儿童（比值，1.21-1.39；P ≤ 0.01）。相反，使用退热药物的儿童调整后的几何平均滴度显著较低（比值，0.80-0.87；P < 0.0006），这取决于病毒株。
不同的分析和报告方法可能导致研究中报告的发热率存在显著差异。需要标准化报告发热，以便于在研究之间进行比较。发热和退热药物的使用可能与儿童流感疫苗免疫原性有重要关联，需要进一步进行前瞻性研究。
