The Incidence of Herpes Zoster Complications: A Systematic Literature Review.

INTRODUCTION: The objective of this work was to summarize the incidence of herpes zoster (HZ) complications in different populations. METHODS: Systematic literature review of PubMed, Embase, and Virtual Health Library records between January 1, 2002 and October 20, 2022 using search strings for HZ, complications, and frequency measurements. RESULTS: The review included 124 studies, most conducted in the general population (n = 93) and on individuals with comorbidities (n = 41) ≥ 18 years of age. Most studies were conducted in Europe (n = 44), Asia (n = 40), and North America (n = 36). Postherpetic neuralgia (PHN) was the most studied neurological complication. Variable relative PHN incidence was found in the general population (2.6-46.7%) or based on diagnosis: immunocompromised (3.9-33.8%), depression (0-50%), and human immunodeficiency virus (HIV) (6.1-40.2%). High incidence rates were observed in hematological malignancies (HM) and solid organ malignancies (132.5 and 93.7 per 1000 person-years, respectively). Ocular complications were frequently reported with herpes zoster ophthalmicus (HZO). The relative incidence (incidence rate) of HZO in the general population was reported as 1.4-15.9% (0.31-0.35 per 1000 person-years). High relative incidence was observed in HIV (up to 10.1%) and HM (3.2-11.3%). Disseminated HZ was the most frequently reported cutaneous complication. The relative incidence of disseminated HZ was 0.3-8.2% in the general population, 0-0.5% in the immunocompetent, and 0-20.6% in patients with comorbidities. High relative incidence was reported in HM and solid organ transplant (up to 19.3% and 14.8%, respectively). DISCUSSION: Most reported complications were neurological (n = 110), ocular (n = 48), and cutaneous (n = 38). Few studies stratified complications by age or gender (or both). Incidence appeared higher in select immunocompromised populations. Higher incidence was associated with older age in several studies; the general association with gender was unclear. CONCLUSIONS: Variable incidence of HZ complications was reported by population subgroup. Further research is required to quantitatively analyze incidence by age, gender, and location.

Herpes zoster in older adults: Impact on carbon footprint in the United States.

We provide estimates for (I) annual herpes zoster (HZ) cases, (II) carbon costs related to healthcare utilization, and (III) annual carbon emissions due to HZ among ≥50 years of age (YOA) United States (US) population. We estimated the annual number of HZ cases in the US based on available incidence data and demographic data of individuals ≥50 YOA. Both the healthcare resource utilization (HCRU) associated with HZ cases and the unit carbon dioxide equivalent (i.e. CO2e) costs associated with each type of HCRU in the US were estimated based on literature and studies available online. The carbon footprint associated with HZ annually among US adults ≥50 YOA was estimated by multiplying the unit carbon estimates by the HCRU. In the US population aged ≥50 YOA in 2020 (i.e. approximately 118 million), approximately 1.1 million cases of HZ occur annually assuming no vaccination. Based on 2 sources of HCRU the average kgCO2e per HZ patient ranged from 61.0 to 97.6 kgCO2e, with values by age group ranging from 40.9 kgCO2e in patients aged 50-59 to 195.9 kgCO2e in patients ≥80 YOA. The total annual HZ associated carbon ranged between 67,000 and 107,000 tons of CO2e in the US population aged ≥50 YOA. The impact of HZ on carbon footprint in the US results in considerable greenhouse gas (GHG)emissions. Assuming no vaccination, the burden of HZ is projected to rise over the coming years with the aging populations consequently worsening its impact on GHG emissions. (Figure 1).

Differential Utility Losses in Herpes Zoster Cases Between Vaccinated and Unvaccinated Subjects: A Meta-analysis of Three Clinical Trials.

BACKGROUND AND OBJECTIVE: Recombinant zoster vaccine (RZV) is approved in adults for the prevention of herpes zoster. The effect of RZV in moderating the severity of breakthrough cases of herpes zoster has been noted but not explicitly quantified before. In this study, a meta-analysis was undertaken to estimate differential utility losses between unvaccinated (Placebo) and vaccinated (RZV) subjects in breakthrough cases of herpes zoster from three RZV clinical trials. METHODS: Differential utility losses between the two groups were estimated in units of quality-adjusted life-years (QALYs), leveraging aggregate patient data from the ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) clinical trials. Differential utility losses and the ratio of mean utility losses were analyzed using random-effects and fixed-effects meta-regression models. RESULTS: The mean QALY loss differences between the unvaccinated (Placebo) and vaccinated (RZV) groups were 0.008, 0.004, and 0.011 in the ZOE-50, ZOE-70, and ZOE-HSCT studies, respectively, yielding an overall estimated difference of 0.007 (95% confidence interval 0.002-0.012) QALYs. Quality-adjusted life-year loss in the vaccinated group was estimated to be 35.5% of the value in the placebo group. A sensitivity analysis estimated an overall difference of 0.005 (95% confidence interval 0.001-0.009) QALYs, corresponding to 48.6% of the QALY loss value in the placebo group. CONCLUSIONS: Recombinant zoster vaccine is effective in alleviating disease severity in breakthrough cases of herpes zoster. The results may be useful in distinguishing QALY losses between vaccinated and unvaccinated cohorts in health economics studies, particularly cost-effectiveness analyses.

Herpes zoster, also known as shingles, may cause painful rashes and persistent pain for months or even years after the initial episode. Recombinant zoster vaccine is approved for the prevention of shingles. Pivotal recombinant zoster vaccine clinical trials have reported data about the impact of shingles episodes on daily activities and overall health-related quality of life. In this work, we combined data from three recombinant zoster vaccine clinical trials and compared the loss in quality of life­measured in quality-adjusted life-years­incurred by vaccinated and unvaccinated subjects who experienced a shingles episode. We found that vaccinated patients experienced lower quality-adjusted life-year losses when they developed shingles compared with unvaccinated patients. Our results may be useful in assessing quality-adjusted life-year losses between vaccinated and unvaccinated cohorts in future herpes zoster vaccination health economics analyses.

Public Health Impact of the Adjuvanted RSVPreF3 Vaccine for Respiratory Syncytial Virus Prevention Among Older Adults in the United States.

INTRODUCTION: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in older adults, resulting in substantial morbidity and mortality. METHODS: This study estimates the public health impact of vaccination with the adjuvanted RSVPreF3 vaccine among adults aged ≥ 60 years in the United States (US). A static, multi-cohort Markov model was used to estimate RSV-related outcomes over a 3-year time horizon for scenarios with and without one-time RSV vaccination. The base-case analysis assumed the same vaccination coverage as for influenza vaccines, with key epidemiology and vaccine inputs obtained from the published literature and phase 3 clinical trial results for the adjuvanted RSVPreF3 vaccine. Model outcomes included the clinical burden of RSV (symptomatic RSV acute respiratory illness [RSV-ARI] cases [classified as upper or lower respiratory tract disease], pneumonia complications, and mortality) and RSV-related healthcare resource use (hospitalizations, emergency department visits, outpatient visits, and antibiotic prescriptions). RESULTS: In the base-case analysis, approximately 56.7 million adults aged ≥ 60 years received the vaccine, resulting in 2,954,465 fewer symptomatic RSV-ARI cases over 3 years compared with no vaccination, including 321,019 fewer X-ray confirmed pneumonia cases and 16,660 fewer RSV-related deaths. Vaccination also prevented a substantial number of RSV-related hospitalizations (203,891), emergency department visits (164,060), outpatient visits (1,577,586), and antibiotic prescriptions (1,343,915) over the 3-year period. A considerable public health impact was observed across a range of sensitivity analyses. CONCLUSIONS: These findings highlight the potential of the adjuvanted RSVPreF3 vaccine to substantially reduce RSV disease burden among US older adults aged ≥ 60 years.

The Impact of the COVID-19 Pandemic on the Incidence of Herpes Zoster: A Narrative Literature Review.

Coronavirus disease 2019 (COVID-19) has had a broad impact on health services and health outcomes. During the pandemic, there were numerous reports of herpes zoster (HZ) in people with COVID-19 and in COVID-19 vaccine recipients. The aim of this review is to elucidate the global effects of the COVID-19 pandemic on HZ. It is postulated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces an immunosuppressive state that favours varicella zoster virus (VZV) reactivation. Three large cohort studies (a multinational study and studies from the USA and Spain) that excluded individuals vaccinated against HZ reported significantly increased risk of HZ following COVID-19 infection, especially in people aged ≥ 50 years. In contrast, a large study from Israel that did not consider HZ vaccination status reported no such increase. Cases of HZ following COVID-19 vaccination have been reported and may be the result of attenuated cell-mediated immunity. This phenomenon appears to vary by vaccine type. Some (but not all) large analyses have reported a significant positive relationship between receipt of mRNA vaccines for COVID-19 and development of HZ. These include analyses of health records databases in Israel and Hong Kong and of spontaneous case reports in the US Vaccine Adverse Event Reporting System (VAERS) database. Routine vaccinations, including shingles vaccine programmes, were disrupted by the COVID-19 pandemic. It is estimated that missed shingles vaccinations may have resulted in 63,117 avoidable HZ cases in the USA. Now that the World Health Organization has declared an end to the COVID-19 pandemic as a health emergency and routine vaccination services have resumed, there is a need to increase awareness of HZ and HZ vaccination.Graphical abstract available for this article.

The respiratory syncytial virus prefusion F protein vaccine attenuates the severity of respiratory syncytial virus-associated disease in breakthrough infections in adults ≥60 years of age.

Background: Respiratory syncytial virus (RSV) is a contagious pathogen causing acute respiratory infections (ARIs). Symptoms range from mild upper respiratory tract infections to potentially life-threatening lower respiratory tract disease (LRTD). In adults ≥60 years old, vaccine efficacy of a candidate vaccine for older adults (RSVPreF3 OA) was 71.7% against RSV-ARI and 82.6% against RSV-LRTD (AReSVi-006/NCT04886596). We present the patient-reported outcomes (PROs) from the same trial at the end of the first RSV season in the northern hemisphere (April 2022). Methods: In this phase 3 trial, adults aged ≥60 years were randomized (1:1) to receive one dose of RSVPreF3 OA vaccine or placebo. PROs were assessed using InFLUenza Patient-Reported Outcome (FLU-PRO), Short Form-12 (SF-12), and EuroQol-5 Dimension (EQ-5D) questionnaires. Peak FLU-PRO Chest/Respiratory scores during the first 7 days from ARI episode onset were compared using a Wilcoxon test. Least squares mean (LSMean) of SF-12 physical functioning (PF) and EQ-5D health utility scores were estimated using mixed effects models. Results: In the RSVPreF3 OA group (N = 12,466), 27 first RSV-ARI episodes were observed versus 95 in the Placebo group (N = 12,494). Median peak FLU-PRO Chest/Respiratory scores were lower in RSVPreF3 OA (1.07) versus Placebo group (1.86); p = 0.0258. LSMean group differences for the PF and EQ-5D health utility score were 7.00 (95% confidence interval [CI]: -9.86, 23.85; p = 0.4125) and 0.0786 (95% CI: -0.0340, 0.1913; p = 0.1695). Conclusions: The RSVPreF3 OA vaccine, in addition to preventing infection, attenuated the severity of RSV-associated symptoms in breakthrough infections, with trends of reduced impact on PF and health utility.

Healthy ageing: Herpes zoster infection and the role of zoster vaccination.

Populations are ageing worldwide, with considerable time lived in ill-health, putting upwards pressure on healthcare budgets. Healthy ageing is defined as maintaining functional ability, including the ability to: meet basic needs; learn, grow and make decisions; be mobile; build and maintain relationships; and contribute to society. The risk and impact of infectious diseases increase with age due to immunosenescence. Vaccination can help to prevent disease in older adults, promoting healthy ageing and active lives. Herpes zoster (HZ) occurs when the varicella zoster virus is reactivated due to declining immunity. HZ is common, with a lifetime risk of one-third, and increases in incidence with age. HZ is associated with severe and intense pain, substantially affecting the functional status of patients as well as their overall health-related quality of life. HZ and its complications may result in prolonged morbidity, including persistent pain (post-herpetic neuralgia, PHN), hearing impairment, vision loss and increased risk of stroke and myocardial infarction. HZ and PHN are difficult to treat, substantiating the benefits of prevention. Vaccines to prevent HZ include a recombinant zoster vaccine (RZV). RZV has shown efficacy against the HZ burden of disease and HZ burden of interference on activities of daily living of over 90% in immunocompetent adults aged ≥50 years. Vaccine efficacy against HZ was maintained at over 70% at 10 years post-vaccination. Adult vaccination, including against HZ, has the potential to reduce burden of disease, thus helping to maintain functioning and quality of life to support healthy ageing in older adults.

Knowledge, Attitudes, and Practices of European Healthcare Professionals towards Hepatitis A and Hepatitis B Vaccination in at-Risk Adults.

Despite the occurrence of several hepatitis A (hepA) and hepatitis B (hepB) outbreaks in Europe in the last few decades, not all European countries have implemented hepA and hepB vaccinations in their national immunization programs, especially for adults at risk for hepA and/or hepB infection, such as men who have sex with men or patients with chronic liver disease. Currently, little is known on the attitudes of European healthcare professionals (HCPs) towards hepA and hepB vaccinations for at-risk adults. We conducted an online survey among HCPs in Germany, Spain, and the United Kingdom to assess their awareness of and adherence to their national hepA and hepB vaccination guidelines for at-risk adults. Among the 698 HCPs who took the survey, most (91.1%) were familiar with their national vaccination recommendations and always followed them or followed them most of the time when advising or prescribing hepA or hepB vaccines. Major and moderate barriers for recommending or administering such vaccines were the non-disclosure of risk factors by the patient (53.0-57.6%) and the patient's lack of motivation or knowledge about the risk of the disease (50.3-52.9%). These results may help inform strategies to improve and accelerate hepA and hepB vaccination in European at-risk adults.

Cost-Effectiveness of Recombinant Zoster Vaccine for the Prevention of Herpes Zoster in Hematopoietic Stem Cell Transplant Recipients and Other Immunocompromised Adults in the United States.

INTRODUCTION: Immunocompromised (IC) adults are at increased risk of developing herpes zoster (HZ) and HZ-related complications due to therapy or underlying disease. This study evaluated the cost effectiveness of recombinant zoster vaccine (RZV) versus no vaccine for the prevention of HZ in hematopoietic stem cell transplant (HSCT) recipients and other IC adults aged ≥ 18 years in the United States (US). METHODS: A static Markov model simulated cohorts of IC individuals using a 1-year cycle length and 30-year time horizon to estimate the cost effectiveness of RZV. Inputs were sourced from clinical trial results and publicly available sources/literature. Modeled populations included US adult HSCT recipients (base case), patients with human immunodeficiency virus (HIV), patients with breast cancer, patients with Hodgkin's lymphoma, and renal transplant recipients. The model reported societal costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity and threshold analyses were conducted. RESULTS: In the base case of 19,671 US adult HSCT recipients, RZV resulted in total societal cost savings of US$0.1 million and 109 incremental QALYs versus no vaccine. RZV was a 'dominant strategy' versus no vaccine because vaccination resulted in cost savings with QALY gains. RZV was also cost saving in renal transplant recipients, and cost effective at a willingness-to-pay threshold of US$100,000 per QALY gained in patients with HIV, breast cancer, and Hodgkin's lymphoma, with ICERs of US$33,268, US$67,682, and US$95,972 per QALY gained, respectively, versus no vaccine. CONCLUSIONS: Model results show RZV is potentially cost saving for the prevention of HZ in US adult HSCT recipients and US adults with selected immunocompromising conditions, and cost effective for others, supporting the use of RZV to prevent HZ and HZ-related complications in IC adults.

Recombinant zoster vaccine in immunocompetent and immunocompromised adults: A review of clinical studies.

Herpes zoster (HZ) is a debilitating vaccine-preventable disease. Impairment of cell-mediated immunity, as observed with aging and immunosuppressive disorders and therapies, increases risk. Recombinant zoster vaccine (RZV) is efficacious against HZ in adults aged ≥50 years in different settings, and in immunocompromised adults aged ≥18 years who are at increased risk of developing HZ. RZV is the first and only HZ vaccine approved for use in immunocompromised adults globally, including in Europe and the US. RZV has a clinically acceptable safety profile and elicits robust immune responses in adults aged ≥50 years, and in immunocompromised adults aged ≥18 years who are at increased risk of HZ. Additionally, RZV is efficacious against HZ complications such as post-herpetic neuralgia and HZ-related pain. This review updates knowledge from a randomized controlled trial setting on the efficacy, safety, immunogenicity, and impact on quality of life of RZV.

What is the context?The varicella zoster virus, which causes chickenpox in childhood, can reactivate in adults and trigger a painful rash called herpes zoster (HZ) or shingles. Almost all adults are at risk of developing HZ as they age or develop risk factors for HZ. Two key studies published in 2015 and 2016 (ZOE-50 and ZOE-70) compared the recombinant zoster vaccine (RZV) with placebo and showed that RZV could effectively prevent HZ in adults aged ≥50 years and ≥70 years, respectively. Several clinical studies were carried out in subsequent years, assessing how effective and safe RZV is compared with a placebo/control in different populations. Based on these studies, RZV was approved for use in adults aged ≥50 years and those aged ≥18 years at increased risk of HZ (European Union) due to immunodeficiency or immunosuppression caused by known disease or therapy (United States).What is new?We reviewed clinical studies of RZV published between 1 January, 2015 and 31 October, 2022. The evidence shows that RZV is effective and does not cause safety concerns across the studied populations, including adults aged ≥50 years and immunocompromised adults aged ≥18 years who are at increased risk of HZ.What is the impact?The growing amount of knowledge on the efficacy, safety, immunogenicity, and impact on quality of life of RZV should assist in deciding to vaccinate and in ensuring that the individuals who could benefit the most from RZV have access to vaccination.

The potential impact of increased recombinant zoster vaccine coverage on the burden of herpes zoster among adults aged 50-59 years.

INTRODUCTION: Recombinant zoster vaccine (RZV) is recommended in the US for prevention of herpes zoster (HZ) in adults aged ≥50 years. Vaccination rates remain suboptimal for adults 50-59 years compared with adults ≥50 years overall. The objective of this study was to model changes in outcomes associated with improved RZV vaccination coverage in US adults 50-59 years. METHODS: A multicohort Markov model compared a scenario using real-world vaccination coverage for US adults 50-59 years in 2020 versus scenarios assuming higher coverage. Outcomes, based on a lifetime horizon, included HZ cases and complications avoided, quality-adjusted life-years (QALY), and costs. Model inputs included HZ epidemiology, RZV vaccine efficacy, coverage, adverse events, and costs, based on published literature and US sources. Some inputs were updated from previous models, including real-world estimates of RZV coverage, series completion, and reflecting longer-term data on waning of vaccine efficacy. The model utilized a cohort size of 42,756,488 individuals based on the 2020 US population census. RESULTS: The model projected that increasing RZV coverage in adults 50-59 years from 7.3 % to 14.6 % (to coverage for adults 60-64 years in 2020) would avoid an additional 504,468 HZ cases, 42,077 postherpetic neuralgia cases, and 56,247 cases of other HZ-associated complications. The increase in vaccine coverage would result in higher vaccination-related costs of $1,172,411,566, but the avoided HZ cases and complications would be expected to result in direct cost savings of $721,973,386 and indirect cost savings of $593,497,480 from avoided productivity loss. Overall, a gain of 5,230 discounted QALYs and cost savings of $143,059,299 from a societal perspective would be realized. CONCLUSION: Modestly higher RZV coverage in US adults 50-59 years could reduce the clinical burden associated with HZ and may result in societal cost savings. These findings demonstrate the potential value of increasing RZV vaccination in this population.

An Analysis of How Herpes Zoster Pain Affects Health-related Quality of Life of Placebo Patients From 3 Randomized Phase III Studies.

OBJECTIVES: Herpes zoster (HZ) is a painful condition caused by the reactivation of the varicella-zoster virus, negatively affecting the lives of patients. In this post hoc analysis, we describe the impact of HZ pain on the health-related quality of life (HRQoL) and activities of daily living (ADL) of immunocompetent individuals 50 years of age and older and in hematopoietic stem cell transplantation (HSCT) recipients age 18 years of age and older. MATERIALS AND METHODS: ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) were phase III, randomized studies conducted in immunocompetent adults 50 years of age and older and 70 years of age and older and in HSCT recipients age 18 years of age and older, respectively. This analysis was performed on patients who experienced an HZ episode in the placebo groups. The impact of varying levels of HZ pain on HRQoL and ADL was analyzed using data from the Zoster Brief Pain Inventory (ZBPI) and the Short Form Health Survey 36 (SF-36) and EQ-5D questionnaires. RESULTS: A total of 520 immunocompetent and 172 HSCT individuals with HZ were included. SF-36 and EQ-5D domain scores showed a significant relationship between increased HZ pain and worsening HRQoL. For every increase of 1 in the ZBPI pain score, the estimated mean decrease (worsening) in score in the ZOE-50/70 and ZOE-HSCT, respectively, was 2.0 and 2.4 for SF-36 Role Physical; 2.1 and 1.8 for SF-36 Social Functioning; and 0.041 and 0.045 for EQ-5D utility. Sleep and General activities were the ADL components most affected. DISCUSSION: Moderate and severe HZ pain had a substantial negative impact on all aspects of HRQoL and ADL. This impact was independent of age and immunosuppression.

Lifetime risk of herpes zoster in the population of Beijing, China.

Objectives: We aimed to estimate the current and future lifetime risks (LTR) of herpes zoster (HZ) and postherpetic neuralgia (PHN), as well as their respective number of annual incident cases in Beijing, China, if individuals were not vaccinated against HZ. Study design: Mathematical model built in Microsoft Excel, de novo. Methods: A hypothetical cohort of 1,000 people was simulated from age 0-100 or until death to generate LTRs of HZ/PHN in Beijing, China. LTR was defined as the risk of developing HZ/PHN at least once in the person's lifetime. The current number of annual incident HZ/PHN cases were also calculated by multiplying up-to-date population data and the annual age-specific incidence of HZ/PHN. For both LTR and annual incident cases, current estimates were projected into the year 2035 to investigate the impact of an aging population. Scenario and deterministic sensitivity analyses (DSA) were conducted to validate the model outcomes. Results: In Beijing, the current and future LTRs of HZ (PHN) were 32.4% (2.8%) and 34.8% (3.3%), respectively. The current and future annual incident cases of HZ (PHN) of individuals aged ≥50 years were 68,394 (7,801) cases among 7.04 million individuals and 88,676 (9,649) cases among 9.08 million individuals, respectively. The scenario analyses demonstrated that modelled results were likely to underestimate the LTR of HZ. Results were robust under the DSA. Conclusions: Given an aging population, HZ poses a significant, growing burden on individuals, the society, and healthcare system of China, highlighting the need for preventative measures such as vaccination.

Public health impact of recombinant zoster vaccine for prevention of herpes zoster in US adults immunocompromised due to cancer.

Individuals who are immunocompromised (IC) due to therapy or underlying disease are at increased risk of herpes zoster (HZ). This study evaluates the public health impact of recombinant zoster vaccine (RZV) relative to no HZ vaccination for the prevention of HZ among adults aged ≥18 years diagnosed with selected cancers in the United States (US). A static Markov model was used to simulate three cohorts of individuals who are IC with cancer (time horizon of 30 years; one-year cycle length): hematopoietic stem cell transplant (HSCT) recipients, patients with breast cancer (BC; a solid tumor example), and patients with Hodgkin's lymphoma (HL; a hematological malignancy example). Cohort sizes reflect the estimated annual incidence of each condition in the US population (19,671 HSCT recipients, 279,100 patients with BC, and 8,480 patients with HL). Vaccination with RZV resulted in 2,297; 38,068; and 848 fewer HZ cases for HSCT recipients, patients with BC, and patients with HL, respectively (each versus no vaccine). Vaccination with RZV also resulted in 422; 3,184; and 93 fewer postherpetic neuralgia cases for HSCT, BC, and HL, respectively. Analyses estimated the quality-adjusted life years gained to be 109, 506, and 17 for HSCT, BC, and HL, respectively. To prevent one HZ case, the number needed to vaccinate was 9, 8, and 10, for HSCT, BC, and HL, respectively. These results suggest RZV vaccination may be an effective option to significantly reduce HZ disease burden among patients diagnosed with selected cancers in the US.

Shingles cases can be prevented by recombinant zoster vaccine (RZV). People who have a weakened immune system (immunocompromised) due to disease or therapy are more likely to develop shingles. For example, shingles occurs in nearly a quarter of patients receiving immunosuppressive treatment for blood cancers. To estimate the public health impact of vaccination against shingles in people who are immunocompromised due to cancer in the United States (US), we used a model to simulate groups with selected types of cancer. The results indicate vaccination with RZV can significantly reduce shingles cases and related complications among these groups in the US.

Cost-effectiveness of the recombinant zoster vaccine (RZV) against herpes zoster: An updated critical review.

The objective of this study was to critically review the cost-effectiveness (CE) of the recombinant zoster vaccine (RZV) against herpes zoster (HZ). A literature review was conducted in PubMed, Embase, and Cochrane between January 1, 2017, and February 28, 2022, and on select public healthcare agency websites to identify and collect data from CE studies comparing RZV to zoster vaccine live (ZVL) or to no vaccination. Study characteristics, inputs, and outputs were collected. The overall CE of RZV was assessed. RZV vaccination against HZ is cost-effective in 15 out of 18 studies included in the present review. Varying incremental cost-effectiveness ratios (ICERs) observed may be associated with different assumptions on the duration of protection of RZV, as well as different combinations of structural and disease-related study (model) inputs driving the estimation of ICERs.

What is the context?• Herpes zoster, also known as shingles, may cause painful rashes and skin alterations.• Chronic pain, also referred to as post-herpetic neuralgia, may persist for months or even years after the initial rash.• The disease is caused by reactivation of the varicella zoster virus.• The recombinant zoster vaccine (RZV) and the zoster vaccine live (ZVL) are approved for the prevention of herpes zoster and post-herpetic neuralgia.• We reviewed published evidence from the past 5 years on RZV.What is new?• Out of 18 selected studies, RZV vaccination against herpes zoster and post-herpetic neuralgia is cost-effective in 15.• In the 15 studies establishing RZV cost-effectiveness, RZV is always cost-effective or frequently cost-saving in direct comparisons to ZVL, when applicable.• RZV was found cost-saving in several immune-compromised populations.What is the impact?• The overview of the currently available body of evidence related to cost-effectiveness of RZV may help informing decision makers about the value of vaccination against herpes zoster.

Adjuvanted recombinant zoster vaccine decreases herpes zoster-associated pain and the use of pain medication across 3 randomized, placebo-controlled trials.

ABSTRACT: Herpes zoster (HZ) and HZ-associated pain greatly affect patients' quality of life, particularly in older and immunocompromised adults, for whom comorbidities and polypharmacy are often reported. Three phase III, randomized, placebo-controlled clinical trials have reported the adjuvanted recombinant zoster vaccine (RZV) as highly efficacious in preventing HZ and reducing pain severity in healthy adults ≥50 years old (Zoster Efficacy Study [ZOE]-50 study, NCT01165177) and ≥70 years old (ZOE-70; NCT01165229) and in immunocompromised adults ≥18 years old undergoing autologous hematopoietic stem cell transplantation (ZOE-HSCT; NCT01610414). Here, we investigated efficacy of RZV in reducing (i) the duration of clinically significant pain (Zoster Brief Pain Inventory pain score ≥3) and (ii) HZ-associated pain medication use and duration of use in participants with confirmed HZ ("breakthrough cases") from the 3 studies. Recombinant zoster vaccine effectively reduced the duration of clinically significant HZ-associated pain during HZ episodes by 38.5% ( P -value: 0.010) in the ZOE-HSCT study. Although a similar trend was observed in the ZOE-50 and ZOE-70 studies, the results were not statistically significant because of the high vaccine efficacy (VE) against HZ resulting in rare breakthrough cases. VE in reducing pain medication use (39.6%; P -value: 0.008) and duration of medication use (49.3%, P -value: 0.040) was reported in the ZOE-70 study; corresponding positive VE estimates were observed in the ZOE-50 and ZOE-HSCT studies but were not statistically significant. Data reported here demonstrate efficacy of RZV in reducing HZ-associated pain duration and pain medication use in breakthrough cases, thereby improving quality of life of those with HZ.

Natural History of Herpes Zoster in the Placebo Groups of Three Randomized Phase III Clinical Trials.

INTRODUCTION: The risk of herpes zoster (HZ) is associated with a decline in immune system function, linked to aging and/or immunocompromising or immunosuppressive diseases or therapies. In this post hoc analysis we describe the incidence of HZ, rash characteristics, and burden of HZ pain in immunocompetent adults ≥ 50 years of age (YOA) and in hematopoietic stem cell transplantation (HSCT) recipients ≥ 18 YOA. METHODS: ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) were phase III, observer-blind, placebo-controlled, randomized studies conducted in immunocompetent adults ≥ 50 YOA and ≥ 70 YOA; and in HSCT recipients ≥ 18 YOA, respectively. A similar methodology for study design, case definition, and data collection were applied in all three studies. The participants received either two doses of the adjuvanted recombinant zoster vaccine or placebo, 1-2 months apart. This analysis focuses on all confirmed HZ cases from the placebo groups of the three studies. HZ pain and interference with activities of daily living were assessed using the Zoster Brief Pain Inventory instrument. RESULTS: Overall, 280, 240, and 172 placebo participants with an HZ confirmed episode aged ≥ 50, ≥ 70, and ≥ 18 YOA were included in the ZOE-50, ZOE-70, and ZOE-HSCT analyses, respectively. The incidence of HZ was 9.1/1000 person-years in both the ZOE-50 and ZOE-70 placebo groups and 95.6/1000 person-years in the ZOE-HSCT study placebo group. In the three studies, most individuals with HZ had severe pain, with approximately 90% of individuals reporting clinically significant pain. An estimated 12.3%, 16.9%, and 21.8% of patients in the ZOE-50, ZOE-70, and ZOE-HSCT studies, respectively, developed post-herpetic neuralgia. CONCLUSION: The incidence and burden of HZ is high in immunocompetent adults aged ≥ 50 YOA and even more so in HSCT recipients aged ≥ 18 YOA.

An Easy-to-Implement Clinical-Trial Frailty Index Based on Accumulation of Deficits: Validation in Zoster Vaccine Clinical Trials.

Purpose: Despite being among those most in need of protection, frail older adults are often not well represented in clinical trials. Although frailty likely influences responses to treatments and vaccines, frailty may not be explicitly considered in trials even when frail participants are enrolled due to the perception that frailty is difficult to measure effectively and efficiently without adding to participant or data collection burden. We developed an easy-to-implement frailty index, the Clinical Trial-Frailty Index (CT-FI), based on baseline medical history and standard patient-reported outcomes using data from clinical trials of recombinant Zoster vaccine (the ZOE-50 and ZOE-70 studies). Our objective was to demonstrate that the CT-FI is a robust measure that may be used retrospectively or prospectively in clinical trials where sufficient patient data have been collected. Methods: The CT-FI was based on baseline medical history and Quality of Life questionnaires (SF-36 and EQ-5D). Items meeting criteria for inclusion were scored from 0 to 1, then summed for each participant and divided by the total number of deficits considered. Validation analyses included descriptive verification of distribution and age- and sex-associations in relation to usual patterns of the frailty index, regressions in relation to outcomes hypothesized to be related to frailty, and resampling methods within the index. Results: The CT-FI distribution was well represented by a gamma distribution with a range of 0-0.70. Deficit accumulation increased with chronological age and was higher for females. Multivariate Cox regression survival analysis showed that the CT-FI, age, and sex were significant predictors of mortality. Jackknife and Bootstrap resampling methods highlighted the robustness of the CT-FI, which was not sensitive to inclusion/exclusion of specific individual or groups of variables. Conclusion: We have developed a reliable, robust and easy-to-implement CT-FI with potential retrospective or prospective application in other clinical trials.

Cost-Effectiveness Analysis Update of the Adjuvanted Recombinant Zoster Vaccine in Japanese Older Adults.

INTRODUCTION: This study aimed to update cost-effectiveness and public health impact estimates of the two-dose recombinant zoster vaccine (RZV) compared with no vaccination against herpes zoster (HZ) in the Japanese population aged 65 years. List price of the vaccine and latest RZV efficacy and waning estimates were incorporated. METHODS: A multicohort static Markov model with a cycle length of 1 year was used to follow a hypothetical cohort of one million people aged 65 years over their remaining lifetime (base case). Age-stratified vaccine efficacy and waning rates were updated on the basis of the latest clinical trial data (interim ZOE-LTFU; NCT02723773). First-dose coverage was assumed at 40%, and second-dose compliance was assumed at 95%. Costs and outcomes were discounted at 2% annually, and the incremental cost-effectiveness ratio (ICER) was calculated from payer and societal perspectives. The societal perspective considered productivity loss due to suffering HZ, or due to suffering HZ and time required for vaccination. Sensitivity analyses explored the overall uncertainties in the model. Scenario analyses for Japanese adults aged 50, 60, 70, 80, ≥ 50, and ≥ 65 years (main scenario) were conducted. An ICER below ¥5-6 million/quality-adjusted life-year (QALY) was considered cost-effective. RESULTS: RZV was estimated to prevent 71,423 HZ cases and 15,858 post-herpetic neuralgia (PHN) cases per million people aged 65 years compared with no vaccine in Japan. The ICER was ¥4,205,515 from a payer perspective and was most sensitive to assumptions regarding vaccine efficacy waning, proportion of patients with HZ developing PHN, and HZ incidence. From societal perspectives, ICERs were ¥3,854,192 (productivity loss from suffering HZ only) and ¥4,622,212 (productivity loss from suffering HZ and time required for vaccination). Overall, the results were considered robust under extensive sensitivity and scenario analyses. CONCLUSION: Vaccination against HZ with RZV is cost-effective compared with no vaccination in Japanese adults aged 65 years.

Assessment of estrogen exposure from transdermal estradiol gel therapy with a dried urine assay.

Transdermal estradiol gel is a commonly used menopausal hormone therapy. In research studies investigating the pharmacokinetics and clinical utility of transdermal estradiol gels, serum is often used to measure estradiol levels. Serum results only represent a moment in time during phlebotomy and thus provide little information and allow for limited inference unless serial measurements are performed. In contrast, dried urine may provide a representation of serum estradiol levels over a longer period of time, while also being non-invasive and easier to collect. The primary aim of this study was to evaluate a dried urine method to determine if it may be a viable option for evaluating estrogen exposure resulting from transdermal estradiol gel use. A secondary aim was to explore differences in the urinary estrogen profiles of premenopausal women on no therapy and postmenopausal women who were either on transdermal estradiol gel therapy or no therapy at all. The results of this study demonstrated that the expected dose-proportional changes in estrogen exposure can be observed in the urinary estrogen profile using a GC-MS/MS dried urine assay. The GC-MS/MS assay also showed the differences in the urinary estrogen profiles of premenopausal women, postmenopausal women on estrogen replacement therapy, and postmenopausal women on no therapy.