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Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases.

ABSTRACT: Herpes zoster (HZ) is an opportunistic infection caused by varicella-zoster virus and observed with increasing frequency in patients receiving immunosuppressive therapies. The literature has suggested that the risk of stroke may increase shortly after HZ, but little is known about this association in patients with autoimmune diseases, who are at increased risk of both zoster and stroke.Medicare data from January 1, 2006 through December 31, 2013 were used to identify patients with autoimmune diseases. The outcome of interest was hospitalized stroke. The hypothesis tested was that the incidence of stroke immediately following HZ is increased compared to the incidence of stroke at later time points. Secondary analyses included assessment of the impact of antiviral therapy on subsequent stroke, as well as the influence of varicella-zoster virus-related complications on stroke incidence.The crude incidence of stroke ranged from a high of 2.30 per 100 patient-years (95% confidence interval [95% CI] 0.96-5.52) within 90 days of HZ in patients who had HZ-related cranial nerve complications and did not receive treatment to a low of 0.87 per 100 patient-years (95% CI 0.75-1.02) at 366-730 days in those without complication who received antiviral treatment. After multivariable adjustment for multiple stroke-related factors, the overall incidence rate ratio (IRR) for stroke in the first 90 days after HZ was 1.36 (95% CI 1.10-1.68) compared to stroke occurring at 366-730 days after HZ. The risk was greater for patients with zoster and cranial nerve complications (IRR 2.08 [95% CI 0.99-4.36]). Prompt antiviral therapy was associated with lower incidence of subsequent stroke (IRR 0.83 [95% CI 0.70-0.98]).In patients with autoimmune diseases, incident HZ was associated with as much as a 2-fold increased risk of stroke in the subsequent few months. These data underscore the urgency of developing strategies for reducing the risk of varicella-zoster virus.

SUBMITTER: Calabrese LH

PROVIDER: S-EPMC5548372 | biostudies-other | 2017 Feb

REPOSITORIES: biostudies-other

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Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases.

Calabrese Leonard H LH Xie Fenglong F Yun Huifeng H Winthrop Kevin L KL Baddley John W JW Calabrese Cassandra C Curtis Jeffrey R JR

Arthritis & rheumatology (Hoboken, N.J.) 20170201 2

<h4>Objective</h4>Herpes zoster (HZ) is an opportunistic infection caused by varicella-zoster virus and observed with increasing frequency in patients receiving immunosuppressive therapies. The literature has suggested that the risk of stroke may increase shortly after HZ, but little is known about this association in patients with autoimmune diseases, who are at increased risk of both zoster and stroke.<h4>Methods</h4>Medicare data from January 1, 2006 through December 31, 2013 were used to ide ...[more]

PMID: 27588578

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Project description:The herpes zoster (HZ) vaccine is recommended for adults in the US ages ?60 years who do not have weakened immune systems. It is unclear how the risk of HZ varies according to age and disease conditions in younger patients with autoimmune or inflammatory (AI) diseases. This study was undertaken to evaluate the age-stratified incidence of HZ in patients with AI diseases as compared to older adults for whom the HZ vaccine is currently recommended by the US Centers for Disease Control and Prevention.Using linked data obtained from patients who were insured by US commercial and government health care plans during the period 2007-2010, 7 cohorts of patients with AI diseases were assembled: systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), ankylosing spondylitis (AS), and gout. Two comparator cohorts were also assembled as controls: adult patients with diabetes and adult subjects without AI diseases or diabetic conditions. HZ was identified using diagnostic codes. Age-specific incidence rates (IRs) of HZ were calculated and compared to the IRs of HZ in control subjects ages 61-70 years who were without AI diseases or diabetic conditions.After review of the linked data, the following number of enrollment periods were identified: 8,395 for patients with SLE, 7,916 for patients with IBD, 50,646 for patients with RA, 2,629 for patients with PsA, 4,299 for patients with PsO, 1,019 for patients with AS, 58,934 for patients with gout, 214,631 for control patients with diabetes, and 330,727 for control subjects without AI diseases and diabetic conditions. The respective highest and lowest IRs of HZ during the study were 19.9 per 1,000 person-years in the SLE cohort and 6.8 per 1,000 person-years in the gout cohort, as compared to an IR of 5.3 per 1,000 person-years in control subjects without AI diseases or diabetic conditions. The age-specific IRs of HZ in patients with RA and those with SLE ages ?40 years were 1.5-2 times greater than those observed in older healthy adults (IR 8.5 per 1,000 person-years), for whom the vaccine is currently recommended.SLE, IBD, and RA are AI diseases associated with a higher risk of HZ compared to that in older adults for whom vaccination is currently recommended, suggesting that individuals with these conditions who are as young as age 40 years could potentially benefit from the HZ vaccine.

Project description:Zostavax, a live attenuated vaccine, has been approved in the United States for use in older individuals to reduce the risk and severity of herpes zoster (HZ), also known as shingles. The vaccine is contraindicated in individuals taking anti-tumor necrosis factor alpha (anti-TNF) therapies or other biologics commonly used to treat autoimmune diseases because of the safety concern that zoster vaccine may be associated with a short-term HZ risk. The objective of the study was to examine the use, safety (short-term HZ risk after vaccination), and effectiveness of zoster vaccine in individuals with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and/or inflammatory bowel diseases.We conducted a cohort study of patients aged 50 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and/or inflammatory bowel diseases by using administrative claims data from a nationwide health plan from January 1, 2005, to August 31, 2009. We examined the extent to which zoster vaccine was used; assessed factors associated with vaccine use (Cox proportional hazards regression); and compared the incidence rates of herpes zoster (HZ) between vaccinated and unvaccinated patients.Among 44,115 patients with the autoimmune diseases, 551 (1.2%) received zoster vaccine, and 761 developed HZ. Zoster vaccine use increased continuously after approval in 2006. Younger and healthier patients, those who had an HZ infection within the past 6 months, and those who were not using anti-TNF therapies were more likely to receive the vaccine. Approximately 6% of vaccinated patients were using anti-TNF therapies at the time of vaccination. The incidence rates of HZ were similar in vaccinated and unvaccinated patients (standardized incidence ratio, 0.99; 95% confidence interval, 0.29 to 3.43).Use of the zoster vaccine was uncommon among older patients with autoimmune diseases, including those not exposed to immunosuppressive medications. The short-term risk of HZ did not appear to be increased in vaccinated patients, even among those using immunosuppressive therapies (for example, biologics) at the time of vaccination. However, our study was limited by the small number of vaccinated patients, and further evidence is needed to confirm the vaccine's safety and efficacy in this population.

Project description:Background and purposeHerpes zoster (HZ) is associated with increased risk of stroke, and zoster vaccine live (ZVL, Zostavax) reduces the risk of HZ. No study has examined the association between ZVL (Zostavax) and risk of stroke. Present study examined association between receipt of ZVL (Zostavax) and risk of stroke among older US population.MethodsOur study included 1 603 406 US Medicare fee-for-service beneficiaries aged ≥66 years without a history of stroke and who received ZVL (Zostavax) during 2008 to 2014, and 1 603 406 propensity score-matched unvaccinated beneficiaries followed through to December 31, 2017. We used Cox proportional hazard models to examine association between ZVL (Zostavax) and composite fatal or nonfatal incident stroke outcomes.ResultsDuring a median of 5.1 years follow-up (interquartile range, 3.9–6.7), we documented 64 635 stroke events, including 43 954 acute ischemic strokes and 6727 hemorrhagic strokes, among vaccinated beneficiaries during 8 755 331 person-years. The corresponding numbers among unvaccinated beneficiaries were 73 023, 50 476, and 7276, respectively, during 8 517 322 person-years. Incidence comparing vaccinated to unvaccinated beneficiaries were 7.38 versus 8.57 per 1000 person-years for all stroke, 5.00 versus 5.90 for acute ischemic stroke, and 0.76 versus 0.84 for hemorrhagic stroke (P<0.001 for all difference). Adjusted hazard ratios comparing vaccinated to unvaccinated beneficiaries were 0.84 (95% CI, 0.83–0.85), 0.83 (0.82–0.84), and 0.88 (0.85–0.91) for all stroke, acute ischemic stroke, and hemorrhagic stroke, respectively. The association between ZVL (Zostavax) and risk of stroke appeared to be stronger among younger beneficiaries, beneficiaries who did not take antihypertensive or statin medications and who had fewer comorbid conditions (P<0.05 for interaction) but largely consistent across sex, low-income status, and racial groups.ConclusionsAmong Medicare fee-for-service beneficiaries, receipt of ZVL (Zostavax) was associated with lower incidence of stroke. Our findings may encourage people to get vaccinated against HZ to reduce HZ and HZ-associated stroke risk.

Dataset Information

Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases.

Publications

Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases.

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