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

摘要 咨询委员会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）。非实验性研究表明，灭活的，季节性的， 标准剂量疫苗在减少流感相关住院方面无效或效果甚微， 透析人群的死亡率，高剂量疫苗提供很少或没有额外的保护， 标准剂量的疫苗。两种采用先进技术的疫苗配方， 近年来获得许可。2015年获得许可的佐剂流感疫苗提高了 疫苗抗原的免疫反应，并扩大反应，包括类似的不匹配的病毒 通过异型保护。重组流感疫苗，于2013年（三价）和2017年获得许可 （四价），使用杆状病毒-昆虫细胞系统生产重组流感抗原。证据 表明含佐剂和重组流感疫苗均具有更高的疫苗有效性 与普通人群中的标准剂量疫苗相比。尽管增加了对佐剂的摄取， 和重组流感疫苗在透析人群中，近年来没有大规模的研究 进行了评估，以评估这些新许可的疫苗的使用，有效性或安全性， 透析患者的弱势群体。需要进行一项大型研究， 佐剂和重组疫苗与其他疫苗的比较，并为流感预防方法提供信息， 透析人群。我们提出了一个大型的，非实验性的研究，使用现有的数据，从美国 美国肾脏数据系统（USRDS）检查各种流感病毒的使用、有效性和安全性 在接受透析的ESRD成人患者中接种疫苗。我们的研究规模庞大， 表征佐剂或重组疫苗之间的有效性和安全性的微小差异 疫苗与标准或高剂量疫苗在相同的流感季节。疫苗有效性 分析将纳入广泛的流感相关结果，包括疾病严重程度的标志物。 安全性分析将侧重于流感疫苗接种后先验确定的不良事件。研究设计和 分析将使用稳健的方法来测量和解释混杂偏倚。我们的发现将告诉 透析患者及其提供者关于不同疫苗的风险和益处以及影响疫苗 该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.