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

带状疱疹活疫苗对抗 TNF 使用者的安全性和有效性（VERVE 试验）

• 批准号: 8629238
• 负责人: JEFFREY R. CURTIS
• 金额: $ 62.5万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8629238
• 关键词: Affect; Afferent Neurons; American; Anti-Tumor Necrosis Factor Therapy; Antibodies; Arthritis; Attenuated Live Virus Vaccine; Biological Response Modifier Therapy; Biology; Blindness; Caring; Cellular Immunity; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chickenpox; Childhood; Chronic; Clinical effectiveness; Complication; Data; Disease; Double-Blind Method; Effectiveness; Elderly; Encephalitis; Event; Flare; General Population; Glycoproteins; Health; Health Planning; Herpes zoster disease; Herpesvirus Type 3; Immune response; Immunosuppression; Immunosuppressive Agents; Incidence; Individual; Infection; Injection Site Reaction; Life; Light; Measures; Morbidity - disease rate; Outcome; Outcome Measure; Pain; Patients; Pharmaceutical Preparations; Placebo Control; Placebos; Population; Postherpetic neuralgia; Prevention; Provider; Public Health; Publishing; Quality of life; Randomized; Rheumatoid Arthritis; Rheumatology; Risk; Safety; Serious Adverse Event; T-Lymphocyte; TNF gene; Time; United States Food and Drug Administration; Vaccinated; Vaccination; Vaccines; Virus; base; burden of illness; cell mediated immune response; clinical practice; college; enzyme linked immunospot assay; experience; hearing impairment; immunogenicity; improved; mortality; novel; pragmatic trial; primary outcome; response; rheumatologist; stem; vaccine safety

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.

描述（由申请人提供）：疱疹带状疱疹（Hz）或“带状疱疹”是由无处不在的杂草菌树脂菌病毒（VZV）重新活化的，该病毒（VZV）在儿童虫感染后仍然潜在感官神经元（“ chickhipox”）。据估计，三分之一的个体会在他们的一生中发展出Hz，而受其带状的患者中有20％的人经历了显着的发病率，偶尔死亡。最常见的并发症是疱疹后神经痛，导致慢性疼痛，有时使人衰弱。其他严重的并发症是罕见的，但具有毁灭性，包括脑炎，失明，听力和死亡丧失。 Hz风险被包括类风湿关节炎（RA）在内的各种免疫抑制状态升高，其中风险大约是普通人群的两倍。鉴于RA的Hz疾病负担增加，以及美国人口中的大量RA患者，在这种情况下，HZ的预防具有重大的公共卫生影响。目前，可获得一种现场衰减疫苗（Zostavax（R）），可将HZ发病率降低近70％，但迄今为止，很少有RA患者接受了这种疫苗。食品和药物管理局（FDA），疾病控制中心（CDC）和美国风湿病学院（ACR）考虑接受一些免疫抑制药物（例如生物学疗法）禁忌的活带疫苗。这种禁忌症源于理论上的关注，即这些人可能会从疫苗 - 应变病毒中发展出局部或传播水痘感染。但是，尚无公开的数据表明这些安全问题是有必要的，并且越来越多的观察数据表明，接种此类患者可能是安全的。鉴于1）RA患者的Hz风险升高； 2）显示大多数RA患者未接种Hz的国家数据； 3）该疫苗在普通人群中的高效和安全性，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，安慰剂控制的大型培养试验，以评估接受ARMHTHRISIS患者的现场HZ疫苗接收抗毒药TNF Thrive Atti-Tnf Thrive the Atti-Tnf Threstive的免疫原性，安全性，安全性和长期的效率。