Comparative Effectiveness and Safety of Adjuvanted and Other Influenza Vaccine Technologies Among Patients Receiving Dialysis

摘要 建议接受透析的终末期肾病患者每年接种流感疫苗 免疫实践委员会(ACIP)。非实验研究表明，灭活的、季节性的、 标准剂量的疫苗在减少与流感相关的住院或 透析人群的死亡率，而大剂量疫苗除了提供额外的保护外，几乎没有提供任何额外的保护 这些结果的标准剂量疫苗。使用先进技术的两种疫苗配方 在最近几年获得了许可。2015年获得许可的佐剂流感疫苗增强了 对疫苗抗原的免疫反应，并扩大反应范围，包括类似的错配病毒 通过异型保护。2013年(三价)和2017年获得许可的重组流感疫苗 (四价)，使用杆状病毒-昆虫细胞系统生产重组流感抗原。证据 说明佐剂疫苗和重组流感疫苗都有较高的疫苗效力。 与普通人群中的标准剂量疫苗相比。尽管越来越多的人接受佐剂 和重组流感疫苗在透析人群中的应用近年来，还没有大规模的研究 对这些新批准的疫苗的利用率、有效性或安全性进行了评估 透析患者的弱势群体。需要一项大规模的研究来比较新获得许可的 佐剂疫苗和重组疫苗与其他疫苗的比较，并为预防流感的方法提供信息 透析人群。我们建议使用来自美国的现有数据进行一项大型的非实验研究。 国家肾脏数据系统(USRDS)检查各种流感的使用、有效性和安全性 接受透析的终末期肾病成人患者的疫苗。我们的研究规模之大将使我们能够 佐剂疫苗和重组疫苗在有效性和安全性方面的细微差别 在相同的流感季节，疫苗与标准或高剂量疫苗的对比。疫苗效力 分析将纳入与流感相关的广泛结果，包括疾病严重程度的标志。 安全性分析将重点放在流感疫苗接种后事先确定的不良事件上。研究设计和研究 分析将使用稳健的方法来衡量和解释混杂的偏见。我们的发现将会告诉我们 透析患者和他们的提供者了解不同疫苗的风险和好处及其影响 这项政策的最终目标是减轻这一弱势群体的呼吸道疾病负担。

ABSTRACT Annual influenza vaccination is recommended for patients with ESRD undergoing dialysis by the Advisory Committee on Immunization Practices (ACIP). Non-experimental studies suggest that inactivated, seasonal, standard-dose vaccines are not effective or minimally effective at reducing influenza-related hospitalizations or mortality in the dialysis population, and the high-dose vaccine provides little to no additional protection beyond the standard-dose vaccine for these outcomes. Two vaccine formulations using advanced technologies have been licensed in recent years. The adjuvanted influenza vaccine, licensed in 2015, enhances the magnitude of the immune response to vaccine antigens and broadens the response to include similar mismatched viruses through heterotypic protection. The recombinant influenza vaccine, licensed in 2013 (trivalent) and 2017 (quadrivalent), uses the baculovirus-insect cell system to produce recombinant influenza antigens. Evidence suggests that both the adjuvanted and recombinant influenza vaccines have higher vaccine effectiveness compared to standard-dose vaccines in the general population. Despite increasing uptake of the adjuvanted and recombinant influenza vaccines among the dialysis population in recent years, no large-scale studies have been conducted to evaluate the utilization, effectiveness, or safety of these newly licensed vaccines in the vulnerable population of patients on dialysis. A large study is needed to compare the newly licensed adjuvanted and recombinant vaccines versus other vaccines and to inform influenza prevention approaches in the dialysis population. We propose a large, non-experimental study using existing data from the United States Renal Data System (USRDS) to examine the use, effectiveness, and safety of various influenza vaccines among adult patients with ESRD undergoing dialysis. The large size of our study will allow us to characterize small differences in vaccine effectiveness and safety between adjuvanted or recombinant vaccines vs. standard or high-dose vaccines during the same influenza seasons. Vaccine effectiveness analyses will incorporate a broad range of influenza-related outcomes, including markers of severity of illness. Safety analyses will focus on a priori identified adverse events after influenza immunization. Study design and analyses will use robust methods to measure and account for confounding bias. Our findings will inform dialysis patients and their providers about the risks and benefits of different vaccines and influence vaccine policy, with the ultimate goal of reducing the burden of respiratory disease in this vulnerable population.