Higher Risk Of Herpes Zoster Research Articles

Tofacitinib as Induction and Maintenance Therapy in Japanese Patients with Active Ulcerative Colitis

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor approved in Japan for the treatment of ulcerative colitis (UC). Differences in the safety profile of tofacitinib in Japanese patients versus the global population, such as a higher risk of herpes zoster, have been reported. Objectives: We conducted post hoc analyses of tofacitinib treatment in Japanese patients with moderate-to-severe UC in two global phase III studies. Methods: In OCTAVE Induction 1 (NCT01465763), 62 patients were randomized to placebo or tofacitinib 10 mg twice daily (b.i.d.). In OCTAVE Sustain (NCT01458574), 39 patients with clinical response in OCTAVE Induction 1 were re-randomized to placebo, tofacitinib 5 mg, or 10 mg b.i.d. Efficacy endpoints included: remission (primary endpoint; total Mayo score ≤2; no individual subscore >1; rectal bleeding subscore 0); mucosal healing (Mayo endoscopic subscore ≤1); clinical response (≥30% and ≥3-point decrease from induction study baseline total Mayo score; decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1). Adverse events (AEs) and clinical laboratory parameters were recorded. Results: At week 8 of OCTAVE Induction 1, 22.4% of patients achieved remission with tofacitinib (placebo, 7.7%). At week 52 of OCTAVE Sustain, 31.3% and 66.7% of patients receiving tofacitinib 5 and 10 mg b.i.d., respectively, achieved remission (placebo, 9.1%). The occurrence of AEs or serious AEs in Japanese patients was generally similar to that in the global study population, with no new or unexpected safety risks observed. Conclusions: Although patient numbers were small, tofacitinib demonstrated numerically greater efficacy versus placebo among Japanese patients in OCTAVE Induction 1 and OCTAVE Sustain, with a safety profile consistent with that of the global study population.

The risk of herpes zoster in patients with ankylosing spondylitis: Analysis of the Korean National Health Insurance Service – Sample cohort database

Objectives: The aims of our study were to determine whether the use of conventional disease-modifying antirheumatic drugs (cDMARDs) or tumor necrosis factor α (TNFα) inhibitors increase the risk of herpes zoster (HZ) in patients with ankylosing spondylitis (AS).Methods: We searched the South Korean National Health Insurance Service – National Sample Cohort Database for relevant patient records between 2002 and 2013. We evaluated the incidence of HZ by categorizing patients into in three treatment groups: disease-modifying antirheumatic drug (DMARD) nonusers, cDMARD users and TNFα inhibitor users.Results: Incidence rates of HZ was 11.0 per 1000 person-years in patients with AS. The adjusted hazard ratio of HZ was higher in cDMARD and TNFα inhibitor users than in DMARD nonusers. In subgroup analyses, current treatment with a TNFα inhibitor increased the risk of HZ significantly both in female patients and in patients aged 50 years or older, but not in patients taking steroids, compared to DMARD nonusers.Conclusions: Treatment with either TNFα inhibitors or cDMARDs is associated with a higher risk of HZ, especially in female patients and older patients, and these two patient groups could therefore benefit from HZ vaccination.

Increased risk of herpes zoster in children with cancer: A nationwide population-based cohort study.

Herpes zoster is rare in healthy children, but immunocompromised persons have an increased risk of herpes zoster and severe diseases. Considering the very limited information on herpes zoster in children with cancer, we performed a nationwide population-based cohort study to estimate the incidence of herpes zoster in children with cancer and to explore the association between the 2 diseases.Data were obtained from the National Health Research Institutes Database in Taiwan. A total of 4432 children with newly diagnosed cancer between 2000 and 2007 were identified as the cancer cohort, and 17,653 children without cancer frequency-matched by sex and age at entry were considered the noncancer cohort. The association between herpes zoster and childhood cancer was determined.Children with cancer had a higher risk of herpes zoster. The incidence rate of herpes zoster was higher in the cancer cohort than in the noncancer cohort (20.7 vs 2.4 per 10,000 person-years; IRR = 8.6; 95% CI = 4.8–15.6). The cumulative incidence was significantly higher in the cancer cohort (P < 0.0001). Leukemia, lymphoma, and solid tumor were all associated with the increased risk, and leukemia had the highest magnitude of strength of association.This nationwide population-based cohort study demonstrated that children with cancer were associated with an increased risk of herpes zoster. In addition to early antiviral treatment, vaccination with heat-treated zoster vaccine or adjuvanted subunit vaccine could be an appropriate policy to decrease the incidence in children with cancer.

Association of Herpes Zoster and Type 1 Diabetes Mellitus.

ObjectiveThe purpose of our study was to determine the association of type 1 diabetes mellitus (T1DM) and the risk of herpes zoster (HZ).MethodsIn this cohort study, we selected 4736 patients with T1DM registered in the Catastrophic Illness Patient Database who received insulin therapy before 2003 and 18944 participants without DM who were selected by frequency matched based on sex and age. Cox proportional hazard regression analysis was used to measure the hazard ratios (HRs) of HZ in the T1DM group compared with that in the non-T1DM group.ResultsCox proportional hazard regression analysis showed that the adjusted HR of HZ was 2.38 times higher for patients in the T1DM group (95% CI = 1.77–3.19) than for those in the non-T1DM group. According to diabetes severity, mild and serious T1DM patients were associated with a higher risk of HZ (adjusted HR = 2.26, 95% CI = 1.67–3.05; and adjusted HR = 5.08, 95% CI = 2.66–9.71, respectively) than subjects without T1DM.ConclusionPatients with T1DM are at a higher risk of HZ than those without T1DM.

High prevalence of herpes zoster in patients with depression.

Patients diagnosed with depression are at an elevated risk of physical illness. Researchers have noted that depression negatively affects immune function and leads to increased susceptibility to infection, including herpes zoster. Few epidemiologic studies have been conducted on whether patients with depression are at a higher risk of herpes zoster. We conducted a retrospective population-based cohort study to investigate whether depression is associated with an increased risk of herpes zoster. We identified 22,886 patients with depression (ICD-9: 296.2, 296.3, 300.4, and 311) in 2000-2005 from National Health Insurance (Taiwan) claims and selected 91,542 controls, frequency matched by sex, age, and index year. We calculated the risk of herpes zoster (ICD-9: 053) between the 2 cohorts in Cox proportional hazards regression. Incidence of herpes zoster was 1.3 times higher in patients with depression than in controls (4.58 vs 3.54 per 1,000 person-years, respectively), with an adjusted hazard ratio (HR) of 1.11 (95% CI, 1.01-1.21). In subjects aged 45-54 years, those with depression had a significantly higher risk than controls (HR = 1.44; 95% CI, 1.19-1.73). In multivariable analysis, malignant conditions (HR = 1.41; 95% CI, 1.15-1.72), rheumatic diseases (HR = 1.28; 95% CI, 1.14-1.44), hyperlipidemia (HR = 1.24; 95% CI, 1.14-1.36), renal diseases (HR = 1.21; 95% CI, 1.08-1.36), anxiety (HR = 1.21; 95% CI, 1.07-1.38), sleep disorder (HR = 1.20; 95% CI, 1.09-1.31), and hypertension (HR = 1.11; 95% CI, 1.02-1.21) were potential risk factors for herpes zoster. Patients diagnosed with depression are at an elevated risk of herpes zoster, particularly those aged 45 to 54 years and those with comorbidities, including renal diseases, hyperlipidemia, malignant conditions, rheumatic diseases, hypertension, anxiety, and sleep disorder.

Dyshidrosis is a risk factor for herpes zoster.

Endogenous factors such as stress-induced immune system reactivity were also associated with dyshidrosis. Herpes zoster (HZ) incidence has been demonstrated to increase with immune deficiencies. Therefore, a relationship between dyshidrosis and HZ may exist. This study investigated whether there is an association between dyshidrosis and HZ. We conducted a population-based cohort study by using Taiwan's Longitudinal Health Insurance Database (LHID2000) records from 1996 to 2011. The dyshidrosis group comprised 8488 patients with newly identified dyshidrosis and no history of HZ prior to diagnosis of dyshidrosis. For the non-dyshidrosis group, each dyshidrosis patient frequency matched according to age (5-year intervals), sex and index date year with four controls selected randomly from the LHID2000. After adjustments for confounding risk factors, the hazard ratio for HZ in the dyshidrosis group was 1.31 compared with the non-dyshidrosis group. Regardless of comorbidities, patients with dyshidrosis had a higher risk of HZ than did controls without dyshidrosis. Patients with more hospital visits that were due to dyshidrosis had a higher risk of HZ. Dyshidrosis is strongly associated with HZ. Patients treated for dyshidrosis should be warned of HZ risk.

Association Between the Initiation of Anti–Tumor Necrosis Factor Therapy and the Risk of Herpes Zoster

Herpes zoster reactivation disproportionately affects patients with rheumatoid arthritis (RA). It is unclear whether anti-tumor necrosis factor (anti-TNF) therapy elevates herpes zoster risk. To ascertain whether initiation of anti-TNF therapy compared with nonbiologic comparators is associated with increased herpes zoster risk. We identified new users of anti-TNF therapy among cohorts of patients with RA, inflammatory bowel disease, and psoriasis, psoriatic arthritis, or ankylosing spondylitis from 1998 through 2007 within a large US multi-institutional collaboration combining data from Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and national Medicaid/Medicare programs. We compared herpes zoster incidence between new anti-TNF users (n=33,324) and patients initiating nonbiologic disease-modifying antirheumatic drugs (DMARDs) (n=25,742) within each inflammatory disease cohort (last participant follow-up December 31, 2007). Within these cohorts, we used Cox regression models to compare propensity score-adjusted herpes zoster incidence between new anti-TNF and nonbiologic DMARD users while controlling for baseline corticosteroid use. Incidence of herpes zoster cases occurring after initiation of new anti-TNF or nonbiologic DMARD therapy. Among 33,324 new users of anti-TNF therapy, we identified 310 herpes zoster cases. Crude incidence rates among anti-TNF users were 12.1 per 1000 patient-years (95% CI, 10.7-13.6) for RA, 11.3 per 1000 patient-years (95% CI, 7.7-16.7) for inflammatory bowel disease, and 4.4 per 1000 patient-years (95% CI, 2.8-7.0) for psoriasis, psoriatic arthritis, or ankylosing spondylitis. Baseline use of corticosteroids of 10 mg/d or greater among all disease indications was associated with elevated risk (adjusted hazard ratio [HR], 2.13 [95% CI, 1.64-2.75]) compared with no baseline use. For patients with RA, adjusted incidence rates were similar between anti-TNF and nonbiologic DMARD initiators (adjusted HR, 1.00 [95% CI, 0.77-1.29]) and comparable between all 3 anti-TNF therapies studied. Across all disease indications, the adjusted HR was 1.09 (95% CI, 0.88-1.36). Among patients with RA and other inflammatory diseases, those who initiated anti-TNF therapies were not at higher risk of herpes zoster compared with patients who initiated nonbiologic treatment regimens.

Increased risk of herpes zoster among 108 604 patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) on certain immunosuppressants have increased herpes zoster (HZ) risk. To determine the risk of HZ in IBD and how antitumour necrosis factor-alpha (anti-TNF) agents affect this risk. We performed a retrospective cohort and nested case-control study using administrative data from IMS LifeLink(®) Information Assets-Health Plan Claims Database. In the cohort, we identified IBD patients <age 64 by diagnosis codes; matched to four individuals without IBD. HZ risk was evaluated by incidence rate ratio (IRR) and adjusted Cox proportional hazards models (HR). In the nested case-control analysis, 2659 IBD patients with HZ were each matched to four IBD patients without HZ. We determined associations between medications and HZ using conditional logistic regression. The cohort included 50 932 patients with Crohn's disease (CD), 56 403 patients with ulcerative colitis (UC) and 1269 with unspecified IBD, matched to 434 416 individuals without IBD. The IBD cohort had increased HZ risk compared with non-IBD (IRR: 1.68, 95% CI: 1.60-1.76). After adjustment, IBD patients had a higher risk of HZ than non-IBD (HR: 1.49, 95% CI: 1.42-1.57). In the nested case-control multivariate-adjusted analyses, anti-TNF medications (OR: 1.81, 95% CI: 1.48-2.21), corticosteroids (OR: 1.73, 95% CI: 1.51-1.99) and thiopurines (OR: 1.85, 95% CI: 1.61-2.13) were independently associated with HZ. Risk of HZ was highest with combination anti-TNF and thiopurine therapy (OR: 3.29, 95% CI: 2.33-4.65). Patients with inflammatory bowel disease are at increased risk for herpes zoster. Use of thiopurines, anti-TNF agents, combination therapy and corticosteroids increases herpes zoster risk.

Herpes zoster in patients taking TNFα antagonists for chronic inflammatory joint disease

Objective To assess the rate of occurrence and outcomes of herpes zoster in patients taking TNFα antagonists. Methods Retrospective review of the medical records of 300 patients who received TNFα antagonists to treat chronic inflammatory joint disease. Results We identified 9 (9/300, 3%) patients who experienced herpes zoster, 6 women and 3 men, with rheumatoid arthritis ( n = 7) or ankylosing spondylitis ( n = 2). The drug was infliximab in 4 patients, adalimumab in 2 patients, and etanercept in 3 patients, including 2 patients with a prior history of infliximab therapy (for 12 and 36 months, respectively). Mean treatment duration at the occurrence of herpes zoster was 27 months (range, 6–42 months). Discussion Glucocorticoid therapy ( n = 7) and methotrexate therapy ( n = 6) were the only risk factors identified in our study. Mean follow-up was 26 months. All 9 patients achieved a full recovery with antiviral treatment and interruption of the TNFα antagonist. One patient experienced a recurrence after resuming TNFα antagonist therapy. Conclusion The scant data in the literature suggest a higher risk of herpes zoster with anti-TNFα antibodies than with the soluble receptor. The role for concomitant treatments (glucocorticoids and methotrexate) should be taken into account.

Clinical and genetic risk factors of herpes zoster in patients with systemic lupus erythematosus.

The aim of this study was to determine the clinical and genetic risk factors that influence herpes zoster occurrence in patients with systemic lupus erythematosus (SLE). Three hundred three SLE patients meeting the American College of Rheumatology criteria were enrolled in this study. Herpes zoster was diagnosed when classic grouped vesicles were noted. Medical records were reviewed retrospectively to collect clinical information. For Fc gamma receptor IIa (Fc gamma RIIa) and Fc gamma RIIIa genotyping, polymerase chain reaction (PCR) using allele-specific primers was performed. The PCR sequence-specific oligonucleotide probe method was utilized in human HLA-DRB1 genotyping. Forty-two cases (13.9%) of zoster occurred among 303 SLE patients. The incidence of zoster in patients with SLE was 32.5/1,000 patients per year. Patients who developed zoster had higher rates of lupus nephritis (P = 0.018) and positive anti-Sm antibody (P = 0.019). However, Fc gamma RIIa and Fc gamma RIIIa polymorphism and the HLA-DRB1 genotype did not influence herpes zoster occurrence. Systemic lupus erythematosus patients with lupus nephritis or anti-Sm antibody are at higher risk of herpes zoster. Fc gamma RIIa (H/R131), Fc gamma RIIIa (F/V176), and HLA-DRB1 genetic polymorphisms did not influence the occurrence of herpes zoster in these patients.

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.