Risk Of Herpes Zoster Infection Research Articles

Increased risk of herpes zoster infection in patients with inflammatory bowel disease: a meta-analysis of cohort studies.

Previous studies have shown increased risk of herpes zoster (HZ) infection in patients with inflammatory bowel disease (IBD). The aim of this study is to better characterize this possible association by conducting a meta-analysis. A comprehensive search of relevant literature until April 30, 2019, was performed. Data on HZ infection and medications in patients with IBD and controls were extracted. The relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were performed to assess the source of heterogeneity. Seven cohort studies were included that involved more than 1,000,000 participants. The RR of HZ infection in patients with Crohn's disease (CD) compared with non-CD patients was 1.74 (95% CI 1.57-1.92, p < 0.001). The pooled RR of HZ infection in patients with ulcerative colitis (UC) compared with non-UC was 1.40 (95% CI 1.31-1.50, p < 0.001). Subgroup analyses revealed that age, race, and publication year contribute to heterogeneity. We also found that steroid users were at increased risk of HZ in CD (OR = 1.78, 95% CI 1.10-2.88). Steroid users and anti-TNFα users were at increased risk of HZ in UC, with RRs of 1.99 (95% CI 1.64-2.42) and 2.29 (95% CI 1.52-3.45), respectively. Begg's test and Egger's test suggested no publication bias. There was a 74% increased risk of HZ infection in patients with CD and 40% increased risk of HZ infection in patients with UC compared with that in non-IBD. IBD patients with high risk of HZ infection may benefit from an HZ vaccine.

Role of janus kinase inhibitors in the treatment of rheumatic diseases

Janus kinases inhibitors (JAKI) are new orally administrable disease-modifying antirheumatic drugs (DMARD) for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), representing a treatment alternative equally effective as biological DMARD that is also classified equivalent in the guidelines. JAKI reversibly inhibit intracellular signal transduction from the cytokine receptor to the nucleus. Tofacitinib and baricitinib, two JAKI already approved for RA treatment, are taken once or twice a day, respectively, and two more are expected to receive approval next year. Tofacitinib is also approved for PsA. Generally, JAKI are initially used in combination with methotrexate (MTX) but are equally effective as monotherapeutic treatment if MTX is contraindicated. In terms of therapy safety, JAKI and bDMARD are generally comparable with one exception: JAKI are associated with an increased risk of herpes zoster infection. JAKI treatment requires laboratory blood tests, especially blood count, transaminases and creatinine. Due to hepatic metabolization, tofacitinib is associated with certain drug interactions. Altogether JAKI enhance treatment possibilities for diseases such as RA and PsA combining the same effectiveness and safety as bDMARD with the option of oral administration.

Association between statin use and herpes zoster: systematic review and meta-analysis

ObjectiveStatins are commonly prescribed worldwide. In addition to being potent lipid-lowering agents, statins have immunomodulating properties that may increase the risk of varicella zoster virus reactivation. This adverse effect may...

Issue Highlights

Issue Highlights

Efficacy of Live Attenuated Herpes Zoster Vaccine in Patients With Inflammatory Bowel Diseases

The risk of herpes zoster virus infection is increased among patients with inflammatory bowel diseases (IBD). The herpes zoster vaccine (HZV) is therefore recommended for these patients, but little is known about its effectiveness, resulting in low use. We conducted a retrospective cohort study using data from the national veterans Affairs Healthcare System (VAHS) from January 1, 2000 through June 30, 2016. We collected data from 39,983 veterans with IBD who had not received the HZV by an age of 60 years. The follow-up period started at age 60 or the date of first IBD medication prescription (whichever was later) and ended with the earliest diagnosis of herpes zoster infection, the end of the study period, or date of death. We identified veterans who received the HZV during the follow-up period and compared the incidence of herpes zoster between vaccinated vs unvaccinated patients. We performed multivariable Cox regression with time-dependent analysis to determine the risk of herpes zoster associated with vaccination status in the entire cohort and stratified by IBD medication. We identified 7170 patients who received the HZV during the follow-up period (17.9% of total cohort; 96.6% male and 94.2% Caucasian). The crude incidence rate of herpes zoster infection during the follow-up period for unvaccinated patients was 6.97/1000 person-years and for vaccinated patients was 4.09/1000 person-years. Vaccination was associated with significantly lower risk of herpes zoster infection, compared to lack of vaccination (adjusted hazard ratio, 0.54; 95% CI, 0.44 - 0.68). Vaccination was associated with a significantly reduced risk of herpes zoster infection among veterans with IBD. This vaccine is therefore effective in patients with IBD, but underused.

Increased Risk of Herpes Zoster Infection in Patients With Inflammatory Bowel Diseases in Korea

Few data are available on risk of herpes zoster (HZ) infection in Asian patients with inflammatory bowel diseases (IBD). We investigated whether patients with IBD in Korea have an increased risk of HZ and sought to identify risk factors for infection. We performed a nationwide population-based study and a hospital-based, nested case-control study. Using the 2009-2013 data from the Korean national health insurance claims database, we calculated incidence rates and standardized incidence ratios (SIRs) of HZ infection in patients with IBD compared with the entire Korean population. In the nested case-control study, within a hospital-based cohort, 300 patients with IBD and HZ infection were matched with 895 patients with IBD without HZ. In the nationwide population-based study, the incidence rate and SIR of HZ infection in patients with IBD were 18.34/1000 person-years and 1.48 (95% CI, 1.42-1.54), respectively. The SIR for HZ infection was higher in patients with Crohn's disease than in patients with ulcerative colitis (1.90 vs 1.36; P < .001) and higher in male patients than female patients (1.63 vs 1.33; P< .001). The incidence rate of HZ increased with age (P trend < .001), whereas the SIR of HZ infection decreased with age (P trend < .001). In the nested case-control study, corticosteroid use was associated with HZ infection (for ulcerative colitis, adjusted odds ratio, 2.44; 95% CI, 1.18-5.05 and for Crohn's disease, adjusted odds ratio, 2.70; 95% CI 1.25-5.83). In a population-based study in Korea, we found patients with IBD to have an increased risk for HZ infection-especially among patients who are male, younger, or have Crohn's disease. Corticosteroid use increases risk of HZ infection in patients with IBD.

Overall and Comparative Risk of Herpes Zoster With Pharmacotherapy for Inflammatory Bowel Diseases: A Nationwide Cohort Study

Patients with inflammatory bowel disease (IBD) might be at increased risk for herpes zoster infection. We sought to quantify the risk of herpes zoster in patients with IBD and evaluate the effects of IBD and IBD medications on the risk of herpes zoster. We conducted 2 retrospective studies of populations of Veterans, from January 2000 through June 2016. In study 1, we compared the incidence of herpes zoster among patients with IBD receiving 5-ASA alone vs matched patients without IBD. In study 2, we compared the incidence of herpes zoster among patients with IBD treated with only 5-ASA, with thiopurines, with antagonists of tumor necrosis factor (TNF), with a combination of thiopurines and TNF antagonists, and with vedolizumab. We used multivariable Cox regression to estimate the hazard ratios and 95% CIs for herpes zoster associated with IBD in study 1 and with different treatments in study 2. We also estimated the incidence rate of herpes zoster based on age and IBD medication subgroups. Compared to no IBD, ulcerative colitis (UC) and Crohn's disease (CD) were each associated with significantly increased risk of herpes zoster infection. In multivariable Cox regression (compared to no IBD), UC, CD, or IBD treated with 5-ASA treatment alone was associated with significantly increased risk of herpes zoster, with adjusted HRs (AHR) of 1.81 for UC (95% CI, 1.56-2.11), 1.56 for CD (95% CI, 1.28-1.91), and 1.72 for treated IBD (95% CI, 1.51-1.96). In multivariable Cox regression analysis, compared to exposure to 5-ASA alone, exposure to thiopurines (AHR, 1.47; 95% CI, 1.31-1.65) or a combination of thiopurines and TNF antagonists (AHR, 1.65; 95% CI, 1.22-2.23) was associated with increased risk of herpes zoster. However, exposure to TNF antagonists alone (AHR, 1.15; 95% CI, 0.96-1.38) was not associated with increased risk of herpes zoster. The incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the oldest group of patients without IBD (older than 60 years). In 2 retrospective studies of Veteran populations, we associated IBD and treatment with thiopurines, alone or in combination with TNF antagonists, with increased risk of herpes zoster. With the approval of a new and potentially safer vaccine for herpes zoster, the effects of immunization of patients with IBD should be investigated.

Ruxolitinib-associated infections: A systematic review and meta-analysis.

Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.

Advances in the Development of Janus Kinase Inhibitors in Inflammatory Bowel Disease: Future Prospects.

Inflammatory bowel disease (IBD) is caused by a dysregulation of the immune system, inducing the production of proinflammatory cytokines and adhesion molecules. A better understanding of the mucosal immune response in IBD has led to the development of new drugs directed at inflammatory cytokines and leukocyte-trafficking molecules. Beyond tumor necrosis factor antagonists and anti-integrin molecules, which act by blocking the interaction between gut-specific lymphocytes and their receptor on vascular endothelium, the Janus kinase/signaltransducer and activator of transcription (JAK/STAT) signaling pathway represents a new target in IBD. JAK inhibitors are small molecules able to selectively target the activity of specific JAKs that play a role in signal transmission via interleukins. This review presents an overview of the role of the JAK/STAT signaling pathway and updated information for JAK molecules, which are promising drugs in IBD. Currently developed to treat ulcerative colitis and Crohn's disease, tofacitinib (in a phase III study) and filgotinib (in a phase II study), respectively, are the JAK inhibitors in the most advanced stage of development for IBD. However, the utility of, and adverse events associated with, these new drugs remain to be determined and clarified (in particular, the risk of herpes zoster infections), depending on the efficacy and tolerance determined from definitive studies. The availability of these drugs could enhance the therapeutic approach to IBD in the coming years, and reinforce the concept of personalized medicine for IBD patients.

Risk of Herpes Zoster and Family History: A Meta-analysis of Case-control Studies.

Background:Herpes zoster (HZ) results from the reactivation of latent varicella zoster virus (VZV) residing in dorsal root and cranial nerve ganglia. Advanced age and dysfunctional cell-mediated immune responses are well-established risk factors for VZV reactivation. There have been recent interests in whether there is an increased risk of the disease associated with a positive family history.Aims and Objectives:We aimed to conduct a meta-analysis to evaluate the association between HZ infection and family history. In addition, we investigated the dose-response relationship between HZ infection and the number of relatives with a history of HZ.Materials and Methods:Observational studies were searched from MEDLINE, EMBASE, and Cochrane Central Register from inception to April 15, 2015. The Meta-analysis of Observational Studies in Epidemiology guidelines were followed in conducting this study. To estimate the pooled odds ratio, random-effects model of DerSimonian and Laird was used. Heterogeneity between studies was assessed using the I2 statistic. A dose-response meta-analysis with studies that reported appropriate data were done using the generalized least squares for trend method.Results:Five studies, yielding a total of 4169 subjects, were identified for meta-analysis. Cases with HZ were 3.03 (95% confidence interval [CI]: 1.86–4.94, P < 0.001) and 3.27 (95% CI: 1.75–6.10, P < 0.001) times more likely to report the first-degree relatives and total relatives with a history of HZ, respectively. A significant positive dose-response relationship between the risk of HZ infection and the number of relatives with a history of HZ was also demonstrated (P < 0.001).Conclusions:This meta-analysis demonstrated that family history is a significant risk factor for HZ infection. This risk has a dose-response relationship with the number of relatives with a history of HZ.

Short-term dipeptidyl peptidase-4 inhibitor use increases the risk of herpes zoster infection in Asian patients with diabetes.

We aimed to evaluate whether patients with diabetes who use dipeptidyl peptidase (DPP)-4 inhibitors are at a higher risk of developing a herpes zoster (HZ) infection. We used a subset of the Longitudinal Health Insurance Database 2000 containing all inpatient and outpatient medical claims of ∼1 million people who were randomly sampled from the National Health Insurance Research Database. Patients who were newly diagnosed with Type 2 diabetes International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM 250.x0 and 250.x2) who used antidiabetic medications were divided into two cohorts based on their use of DPP-4 inhibitors between 2009 and 2011. Cox proportion hazard regression models were used to assess the effects of DPP-4 inhibitors on the incidence of HZ compared with the non-DPP-4-inhibitor-exposed cohort. Patients in DPP-4-inhibitor-exposed cohort with diabetes and HZ infections revealed an incidence density of 4.20 per 1000 person-years compared with 3.50 per 1000 person-years for the non-DPP-4-inhibitor-exposed cohort (adjusted hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 0.70-1.99). Furthermore, high-dose DPP-4-inhibitor treatment was associated with a significantly higher risk of HZ (adjusted HR = 2.46, 95% CI = 1.16-5.19 for a defined daily dose [DDD] ≥ 360). In addition, short-term DPP-4-inhibitor treatment was associated with a significantly higher risk of HZ (adjusted HR = 2.04, 95% CI = 1.03-4.04 for a DDD ≥ 360 days). These results suggest that Asian patients with diabetes who use short-term DPP-4 inhibitors might be at a higher risk of developing HZ.

Statins can increase the risk of herpes zoster infection in Asia.

This study evaluated whether statin therapy increases the risk of herpes zoster (HZ) infection in Asia. This retrospective cohort study used the Longitudinal Health Insurance Database (LHID2000). From the LHID2000, patients aged 20years were divided into two cohorts according to their statin use and were matched at a 1:1 ratio according to propensity scores, which were calculated using a logistic regression for estimating the probability of treatment assignment. The primary outcome was HZ infection. All patients were followed from the index date until the date of HZ infection, withdrawal from the insurance system, or the end of 2011. The study included 53,069 patients receiving statin therapy as a statin cohort and 53,069 patients without statin therapy as a nonstatin cohort. The mean follow-up durations for the statin cohort and nonstatin cohort were 4.89 [standard deviation (SD) = 2.86] years and 4.75 (SD = 2.90) years, respectively. The patients in the statin cohort had a 21% higher risk of contracting HZ infection than the patients in the nonstatin cohort [95% confidence interval (CI) = 1.13-1.29]. The incidence of HZ infection increased with the Charlson comorbidity index (CCI) score in both cohorts. A high mean defined daily dose of the six types of statins considered in this study was associated with a significantly increased risk of HZ infection. Statin therapy can increase HZ infection in Asia. More benefit-risk evaluations for statin use are necessary in Asia.

THU0368 Risk of herpes viruses infections (HSV,VZV) during anti-tnf therapy in patients with inflammatory rheumatic diseases. Systematic review and meta-analysis

BackgroundTNF blockers have demonstrated their efficacy in inflammatory rheumatic diseases (IRD) and are now widely used. A moderate but indubitable increase in bacterial infectious events is known in patients treated...

Association Between Vaccination for Herpes Zoster and Risk of Herpes Zoster Infection Among Older Patients With Selected Immune-Mediated Diseases

Based on limited data, the live attenuated herpes zoster (HZ) vaccine is contraindicated in patients taking anti-tumor necrosis factor (anti-TNF) therapies or other biologics commonly used to treat immune-mediated diseases. The safety and effectiveness of the vaccine are unclear for these patients. To examine the association between HZ vaccination and HZ incidence within and beyond 42 days after vaccination in patients with selected immune-mediated diseases and in relation to biologics and other therapies used to treat these conditions. Retrospective cohort study of 463,541 Medicare beneficiaries 60 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease using Medicare claims data from January 1, 2006, through December 31, 2009. Herpes zoster incidence rate within 42 days after vaccination (a safety concern) and beyond 42 days; hazard ratios estimated using Cox proportional hazards models for HZ comparing vaccinated vs unvaccinated patients. Median duration of follow-up was 2.0 years (interquartile range, 0.8-3.0); 4.0% of patients received HZ vaccine. The overall crude HZ incidence rate was 7.8 cases per 1000 person-years (95% CI, 3.7-16.5) within 42 days after vaccination. The rate among the unvaccinated was 11.6 cases per 1000 person-years (95% CI, 11.4-11.9). Among 633 patients exposed to biologics at the time of vaccination or within the subsequent 42 days, no case of HZ or varicella occurred. After multivariable adjustment, HZ vaccination was associated with a hazard ratio of 0.61 (95% CI, 0.52-0.71) for HZ risk after 42 days. Receipt of HZ vaccine was not associated with a short-term increase in HZ incidence among Medicare beneficiaries with selected immune-mediated diseases, including those exposed to biologics. The vaccine was associated with a lower HZ incidence over a median of 2 years of follow-up.

Low plasma concentrations of retinol and α-tocopherol in hematopoietic stem cell transplant recipients: the effect of mucositis and the risk of infection

Although vitamin deficiencies are rare in the United States, acute reductions in concentrations of plasma retinol (vitamin A) or alpha-tocopherol (vitamin E) have been associated with impaired immune responses in some clinical settings. The objectives were to determine the plasma concentrations of retinol and alpha-tocopherol in patients undergoing dose-intensive therapy and hematopoietic stem cell transplant and to examine the association of plasma concentrations with clinical outcomes reflecting immunity. This was an observational trial of 120 consecutive recipients of hematopoietic stem cell transplant and a multivariate analysis of plasma vitamin concentrations, mucositis, infections in the first 30 d, and herpes zoster infections in the first year after hematopoietic stem cell transplant. Plasma retinol and alpha-tocopherol concentrations declined from baseline to day 7, typically recovering without specific replacement toward baseline by day 14. The severity of mucositis was a strong predictor of low plasma retinol on day 7 (P = 0.001). Eighty-two patients (68%) had at least one plasma retinol concentration < or = 1.05 micro mol/L, a concentration previously determined to be of immunologic significance, during the peritransplant period (day -8 to day 14). Men more frequently acquired herpes zoster than women, and men who developed hyporetinolemia (< or = 1.05 micro mol/L) had a significantly higher risk of herpes zoster (OR: 6.6; 95% CI: 1.5, 29.6). Plasma alpha-tocopherol was not associated with any clinical event measured in this study. Hyporetinolemia is common, particularly in subjects with severe mucositis, and is associated with an increased risk of herpes zoster infection in recipients of hematopoietic stem cell transplant. Additional investigations are required to determine whether these findings indicate a causal relation.

HAART may increase risk of herpes zoster infection

HAART may increase risk of herpes zoster infection