Safety and Effectiveness of Live Zoster Vaccine in Anti-TNF Users (VERVE Trial)

描述（由申请人提供）：带状疱疹（HZ）或“带状疱疹”是由普遍存在的水痘带状疱疹病毒（VZV）重新激活引起的，该病毒在儿童水痘感染（“水痘”）后仍潜伏在感觉神经元中。据估计，三分之一的个体将在其一生中发展HZ，并且>20%的受带状疱疹影响的个体经历显著的发病率和偶尔的死亡率。最常见的并发症是带状疱疹后神经痛，导致慢性疼痛，有时使人衰弱。其他严重的并发症是罕见的，但毁灭性的，包括脑炎，失明，听力丧失和死亡。HZ风险因各种免疫抑制状态而升高，包括类风湿性关节炎（RA），其风险约为一般人群的两倍。鉴于RA中HZ疾病负担的增加，以及美国人群中大量的RA患者，在这种情况下预防HZ具有重大的潜在公共卫生影响。目前，一种减毒活疫苗（Zostavax（r））可使HZ发病率降低近70%，但迄今为止，很少有RA患者接受过这种疫苗;美国食品药品监督管理局（FDA）、疾病控制中心（CDC）和美国风湿病学会（ACR）认为接受某些免疫抑制药物（如生物疗法）的患者禁忌使用活带状疱疹疫苗。这一禁忌症源于理论上的担忧，即这些个体可能因疫苗株病毒而发生局部或播散性水痘感染。然而，没有发表的数据表明这些安全性问题是有必要的，越来越多的观察数据表明，为这些患者接种疫苗可能是安全的。鉴于1）RA患者中HZ风险显著升高; 2）国家数据显示大多数RA患者未接种HZ疫苗;和3）该疫苗在一般人群中的高效性和安全性，我们建议进行水痘带状疱疹疫苗E（VERVE）试验，这是一项随机、双盲、安慰剂对照的大型实用性试验，以评估该疫苗的免疫原性、安全性，以及HZ活疫苗在接受抗TNF治疗的关节炎患者中的长期有效性。

DESCRIPTION (provided by applicant): Herpes zoster (HZ), or "shingles", is caused by reactivation of the ubiquitous varicella zoster virus (VZV) that remains latent in sensory neurons following childhood varicella infection ("chickenpox"). It is estimated that one-third of individuas will develop HZ in their lifetime, and that >20% of individuals affected by zoster experience significant morbidity and occasionally mortality. The most common complication is post-herpetic neuralgia, resulting in chronic and sometimes debilitating pain. Other serious complications are rare but devastating, including encephalitis, blindness, loss of hearing and death. HZ risk is elevated by various states of immunosuppression including rheumatoid arthritis (RA), where the risk is approximately double that of the general population. Given the increased HZ disease burden in RA, and the large numbers of RA patients within the US population, prevention of HZ in this setting has major potential public health impact. Currently, a live attenuated vaccine (Zostavax(r)) is available that reduces HZ morbidity by nearly 70%, yet to date, few RA patients have received this vaccine; the Food and Drug Administration (FDA), Center for Disease Control (CDC), and the American College of Rheumatology (ACR) consider the live zoster vaccine contraindicated in patients receiving some immunosuppressive medications such as biologic therapies. This contraindication stems from the theoretical concern that these individuals could develop local or disseminated varicella infection from the vaccine-strain virus. However, there are no published data to suggest that these safety concerns are warranted, and a growing body of observational data suggest that vaccinating such patients might be safe. In light of 1) a substantial elevated HZ risk among RA patients; 2) national data showing most RA patients are not vaccinated for HZ; and 3) the high effectiveness and safety of this vaccine in the general population, we propose to conduct the Varicella zostER VaccinE (VERVE) trial, a randomized, double-blind, placebo-controlled large pragmatic trial to evaluate the immunogenicity, safety, and longer-term effectiveness of the live HZ vaccine in arthritis patients receiving anti-TNF therapy.