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

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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.