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

描述(申请人提供)：带状疱疹(HZ)，或“带状疱疹”，是由儿童水痘感染(“水痘”)后在感觉神经元中潜伏的无处不在的水痘带状疱疹病毒(VZV)重新激活引起的。据估计，三分之一的人会在他们的一生中患上湿疹，20%的带状疱疹患者会经历严重的发病率和偶尔的死亡。最常见的并发症是带状疱疹后神经痛，导致慢性疼痛，有时还会使人虚弱。其他严重的并发症是罕见的，但具有破坏性，包括脑炎、失明、听力丧失和死亡。包括类风湿性关节炎(RA)在内的各种免疫抑制状态都会增加赫兹风险，后者的风险大约是普通人群的两倍。鉴于类风湿性关节炎增加的疾病负担，以及美国人口中大量的类风湿性关节炎患者，在这种情况下预防类风湿性关节炎具有重大的潜在公共卫生影响。目前，一种减毒活疫苗(Zostavax(R))可以将HZ的发病率降低近70%，但到目前为止，很少有RA患者接种过这种疫苗；食品和药物管理局(FDA)、疾病控制中心(CDC)和美国风湿病学会(ACR)认为，带状疱疹活疫苗是接受一些免疫抑制药物(如生物疗法)的患者禁忌使用的疫苗。这一禁忌症源于理论上的担忧，即这些人可能会因疫苗株病毒而患上局部或播散性水痘感染。然而，没有公布的数据表明这些安全担忧是有根据的，越来越多的观察数据表明，为这类患者接种疫苗可能是安全的。鉴于1)RA患者中HZ风险显著增加；2)国家数据显示大多数RA患者没有接种HZ疫苗；以及3)这种疫苗在普通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(VERVE)试验，这是一项随机、双盲、安慰剂对照的大型务实试验，以评估接受抗肿瘤坏死因子治疗的关节炎患者使用HZ活疫苗的免疫原性、安全性和长期有效性。

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.