Efficacy and serious adverse events profile of the adjuvanted recombinant zoster vaccine in adults with pre-existing potential immune-mediated diseases: a pooled post hoc analysis on two parallel randomized trials.

ABSTRACT OBJECTIVE: In the ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials, the adjuvanted recombinant zoster vaccine (RZV) demonstrated ≥90% efficacy in preventing herpes zoster (HZ) in all age groups ≥50 years. Given the increased HZ risk associated with certain underlying autoimmune diseases or their treatment regimes, we conducted a post hoc analysis of RZV's efficacy against HZ and safety profile [specifically, the occurrence of serious adverse events (SAEs)] in ZOE-50/70 participants who reported pre-existing potential immune-mediated diseases (pIMDs) at enrolment and were not on immunosuppressive therapies. METHODS: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomized to receive two doses of RZV or placebo 2 months apart. In this subgroup analysis of participants with at least one pIMD at enrolment, the efficacy was calculated for two-dose recipients who did not develop confirmed HZ before 30 days post-dose 2. SAE occurrence was evaluated for all participants who received at least one dose. RESULTS: Of the 14 645 RZV and 14 660 placebo recipients from the ZOE-50/70 studies, 983 and 960, respectively, reported at least one pre-existing pIMD at enrolment and were included in these analyses. The most frequent pre-existing conditions were psoriasis, spondyloarthropathy and RA. Efficacy against HZ was 90.5% (95% CI: 73.5, 97.5%) overall with the lowest being 84.4% (95% CI: 30.8, 98.3%) in the 70-79-year-old age group. SAEs and fatal SAEs were similar between RZV and placebo recipients. CONCLUSION: In ZOE-50/70 participants with pre-existing pIMDs, RZV was highly efficacious against HZ and SAE incidence was similar between RZV and placebo recipients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01165177 (ZOE-50), NCT01165229 (ZOE-70).

Analysis of Vascular Event Risk After Herpes Zoster From 2007 to 2014 US Insurance Claims Data.

OBJECTIVE: To estimate the risk of transient ischemic attack (TIA), stroke, and myocardial infarction in periods covering 4 weeks before to 52 weeks after herpes zoster (HZ) diagnosis in US adults. PATIENTS AND METHODS: This retrospective study (GSK study identifier: HO-15-15771) with matched cohorts used the Truven Health MarketScan Commercial and Medicare claims data set linked with obesity and smoking status information. Patients 18 years and older at the date of HZ diagnosis and 1-year pre- and post-HZ diagnosis continuous insurance enrollment (from January 1, 2007, through December 31, 2014) were propensity score matched to controls in terms of demographic characteristics, risk factors for vascular events, other comorbid disorders, general health, obesity, and smoking status. A post hoc sensitivity analysis was performed not matching for obesity and smoking status information. Adjusted incidence rate ratios (IRRs) were estimated using multivariate Poisson models during an aggregate period (1-month before and after the index date). RESULTS: A total of 23,339 patients with HZ were matched to 46,378 controls (mean age, 56 years; 45,173 [65%] women). During the aggregate period, patients with HZ were statistically significantly more likely to suffer a TIA: IRRs for all patients and patients aged 18 to 49 years were 1.56 (95% confidence interval [CI], 1.13-2.15) and 5.12 (95% CI, 1.37-19.10), respectively (P<.05); the respective IRRs for stroke were 1.40 (95% CI, 0.93-2.11) and 8.12 (95% CI, 0.93-71.27). In the sensitivity analysis, IRRs for TIA and stroke were statistically significantly increased regardless of age. CONCLUSION: Herpes zoster was associated with an increased risk of composite events, TIA, and stroke in adults in the period around diagnosis. More research on the HZ and vascular risk association is needed. GSK STUDY IDENTIFIER: HO-15-15771.

Costs of herpes zoster complications in older adults: A cohort study of US claims database.

BACKGROUND/OBJECTIVES: Herpes zoster (HZ) incidence increases with age, and the burden of HZ is expected to grow with aging of populations worldwide. We aim to determine the incremental healthcare resource utilization and associated costs of patients with common HZ-related complications other than postherpetic neuralgia (cutaneous, neurologic and ophthalmic) compared to uncomplicated HZ. METHODS: We conducted a retrospective cohort study of commercial health insurance claims covering about 40 million immunocompetent individuals aged ≥50 years at study entry from all over the US, from 2008 to 2013, with follow-up for one year after HZ onset. All-cause healthcare resource utilization and direct healthcare costs were recorded and calculated from six months before until 12 months after HZ onset. The mean costs for HZ patients with complications were compared to the mean costs for patients with uncomplicated HZ. Multivariable regression analyses estimated mean incremental costs adjusted for demographics, comorbidities, type of complication and time period. RESULTS: Over the five-year study period, 22,948 HZ patients (60% women, median age 62 years) who experienced at least one of the selected complications were compared to 213,232 patients (63% women, median age 61 years) with uncomplicated HZ. Overall, the mean annual incremental unadjusted costs for the patients with HZ-related complications were US$4716, ranging from US$2173 for ophthalmic to US$18,323 for neurologic complications. Most of the incremental costs associated with HZ complications were accrued during the first quarter after HZ onset. For each complication type the incremental costs increased with age up to, but not including the oldest group, aged ≥80 years. CONCLUSIONS: Approximately 10% of immunocompetent older patients with HZ develop complications which considerably increase the economic burden of HZ. Vaccination of older adults will offset some of the burden of HZ, including costs associated with HZ-related complications.

Cost of herpes zoster and herpes zoster-related complications among immunocompromised individuals.

Herpes zoster (HZ) is a painful dermatomal rash caused by reactivation of latent varicella-zoster virus. The incidence of HZ is increased for immunocompromised (IC) individuals. The objective of this study is to assess the healthcare costs incurred by IC individuals who develop HZ with or without associated complications. We conducted a retrospective case-control study across the US over a 5-year period, based on health insurance claims data for individuals aged ≥50 years identified as IC by disease or immunosuppressive treatment. A cohort of 30,107 IC individuals who experienced HZ was matched to a cohort of 113,875 IC individuals without HZ. Average all-cause healthcare costs over 18 months were calculated and compared between IC individuals with and without HZ. In addition, the costs of HZ in IC individuals with HZ-related complications were compared to the costs of those with uncomplicated HZ. During the year following HZ onset, IC individuals with HZ had on average total unadjusted costs that were US$3879 higher than the controls. After adjusting costs, controlling for comorbidities and healthcare costs before the onset of HZ, the average annual costs for HZ cases and controls without HZ were similar. HZ-related complications led to increases in average adjusted annual costs compared to uncomplicated HZ ranging from US$612 for eye complications to US$4535 for neurologic complications. In conclusion, in IC individuals, episodes of HZ lead to substantially increased unadjusted annual healthcare costs. HZ-related complications add considerably to adjusted annual healthcare costs compared to uncomplicated HZ.

Analysis of real-world health care costs among immunocompetent patients aged 50 years or older with herpes zoster in the United States.

Few peer-reviewed publications present real-world United States (US) data describing resource utilization and costs associated with herpes zoster (HZ) and postherpetic neuralgia (PHN). The primary objective of this analysis (GSK study identifier: HO-14-14270) was to assess direct costs associated with HZ and PHN in the US using a retrospective managed care insurance claims database. Patients ≥ 50 y at HZ diagnosis were selected. Patients were excluded if they were immunocompromised before diagnosis or received an HZ vaccine at any time. A subsample of patients with PHN was identified. Each patient with HZ was matched to ≤ 4 controls without HZ based on age, sex, and health plan enrollment. Incremental differences in mean HZ-related costs ("incremental costs") were assessed overall and stratified by age. Multivariable regression models controlled for the effect of demographic characteristics, prediagnosis costs, and comorbidity burden on costs using a recycled predictions approach. Overall, 142,519 patients with HZ (9,470 patients [6.6%] had PHN) and 357,907 matched controls without HZ were identified. Resource utilization was greater among patients with HZ than controls. After adjusting for demographic and clinical characteristics, annual incremental health care costs for HZ patients vs. controls were $1,210 for patients aged 50-59 years, $1,629 for those 60-64 years, $1,876 for those 65-69 years, $2,643 for those 70-79 years, and $3,804 for those 80+ years; adjusted annual incremental costs among PHN patients vs. controls were $4,670 for patients 50-59 years, $6,133 for those 60-64 years, $6,451 for those 65-69 years, $8,548 for those 70-79 years, and $11,147 for those 80+ years. HZ is associated with a significant cost burden, which increases with advancing patient age. Vaccination may reduce costs associated with HZ through case avoidance.