The aim of this study is to observe how many patients develop Herpes Zoster (HZ), also known as shingles, and related complications in adulthood. It also aims to understand how often patients with HZ use the health service and if HZ and its complications result in death.
HZ is a viral infection which happens due to reactivation of the same virus that causes chicken pox. Previous research has shown that older patients and/or patients with conditions that weaken the immune system are more likely to develop HZ in their lifetime.
For this study, we will use general practitioner and hospital records data starting from January 2012. We will include adults who have not had HZ or received the HZ vaccine at the beginning of the study. We will observe patients who are diagnosed with HZ from 2012 and describe what happens to these patients after they are diagnosed. We will describe this for everyone included in the study and in groups of patients with conditions that weaken the immune system and/or other chronic conditions, or none of these conditions.
In the United Kingdom, there is a vaccine currently recommended for patients over 60 years old and for those who are over 50 with weakened immune systems. The results from this study will help assess if the vaccine should be recommended for more patient groups.
This retrospective cohort study will be conducted on adults aged 18 years and above in CPRD Aurum-Hospital Episodes Statistics linked data (01 January 2012 to 31 December 2019) and CPRD Aurum data (01 January 2012 and 30 June 2023). This study will include adults with no history of a herpes zoster (HZ) diagnosis, who have not received an HZ vaccine (zoster vaccine live [ZVL] or recombinant zoster vaccine [RZV]) and have a one-year minimum follow-up before study entry. This overall population will be categorised into an immunocompromising (IC) subpopulation, a chronic subpopulation, an IC-free subpopulation, and a subgroup of patients who are both IC- and chronic-free.
The primary aim of this study is to evaluate the burden of HZ in England, with a focus on estimating the HZ incidence rate within the IC subpopulation. Other key analyses will include assessing HZ incidence and recurrence rates in other subpopulations, describing the socio-demographic characteristics of HZ and non-HZ patients, evaluating the rate of healthcare resource use and associated cost in primary and secondary healthcare settings for HZ patients, risk factors of HZ complications and the mortality rate due to HZ and/or its complications. Continuous and categorical variables will be analysed descriptively i.e., reporting mean, standard deviation, median, interquartile range, minimum and maximum, number and percentage of patients. Annualised and overall rates will be presented as the number of events per 1000 patient-years with 95% confidence intervals. Logistic regression models will be used for the risk factor analysis. Select analyses will be stratified by age group, sex, socioeconomic status (using Index of Multiple Deprivation), practice region and/or condition. The study will provide up-to-date data on the burden of HZ which will help inform plans to expand RZV vaccination to other populations currently not included in the Joint Committee on Vaccination and Immunisation recommendation.
Primary outcomes
Annual and overall incidence rate of herpes zoster (HZ; defined using MedCodes in CPRD Aurum and ICD-10 codes in HES) from 2012 to 2019 in the IC subpopulation (defined using CPRD-HES linkage).
Secondary outcomes
Annual and overall incidence rate of HZ from 2012 to 2019 in the chronic subpopulation, IC-free subpopulation and non-IC and non-chronic subgroup; prevalence of HZ occurrence, IC conditions and chronic conditions from 2012 to 2019 in the overall population; overall rate of HZ complications (postherpetic neuralgia [PHN, developed within 90 to 365 days of initial HZ event], neurological complications, ocular complications, disseminated complications and other HZ-related complications) in the IC subpopulation, chronic subpopulation, IC-free subpopulation and non-IC and non-chronic subgroup; cause-specific mortality rate due to HZ and/or HZ complications (as aforementioned) in the IC subpopulation, chronic subpopulation, IC-free subpopulation and non-IC and non-chronic subgroup; overall rate of all-cause healthcare resource utilisation (HCRU) for inpatient admissions, outpatient visits, accident and emergency visits, general practitioner visits and HZ prescriptions and associated costs of each for HZ patients, PHN patients and PHN-free patients in the IC subpopulation, chronic subpopulation, IC-free subpopulation and non-IC and non-chronic subgroup; incidence rate ratio of HZ for the IC subpopulation vs the non-IC and non-chronic subgroup, and the chronic subpopulation vs the non-IC and non-chronic subgroup; sociodemographic characteristics (age, age group, sex, practice region, ethnicity, smoking status, alcohol consumption, socioeconomic status [using IMD score] at patient and practice level, follow-up time from relevant population index date, and follow-up from HZ index date) for the overall population, IC subpopulation, chronic subpopulation, IC-free subpopulation and non-IC and non-chronic subgroup.
Exploratory outcomes
Proportion of patients who had undergone immune-suppressing treatments in select IC subpopulations (rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, psoriasis/psoriatic arthritis, multiple sclerosis, polymyalgia rheumatica, and autoimmune thyroiditis) and chronic subpopulations (diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, asthma); risk factors (age group, sex, body mass index, smoking status and alcohol consumption) for HZ related complications (as aforementioned) in the IC subpopulation and IC-free subpopulation; annual rate of HZ recurrence in the IC subpopulation and IC-free subpopulation; annual and overall incidence rate of HZ (defined using MedCodes in CPRD Aurum only) from 2012 to 2023 in IC subpopulation (defined using CPRD Aurum only); annual and overall incidence rate of HZ (defined using HZ algorithms) from 2012 to 2019 in the IC subpopulation (defined using CPRD-HES linkage); overall rate of PHN (developed within 365 days of initial HZ event) in the IC subpopulation, chronic subpopulation, IC-free subpopulation and non-IC and non-chronic subgroup; cause-specific mortality rate due to PHN (developed within 365 days of initial HZ event) in the IC subpopulation, chronic subpopulation, IC-free subpopulation and non-IC and non-chronic subgroup; overall rate of all-cause HCRU of inpatient admissions, outpatient visits, accident and emergency visits, general practitioner visits and HZ prescriptions, and associated costs of each, for PHN patients (developed within 365 days of initial HZ event) in the IC subpopulation, chronic subpopulation, IC-free subpopulation and non-IC and non-chronic subgroup.
Caroline O'Leary - Chief Investigator - IQVIA Ltd ( UK )
Karabo Keapoletswe - Corresponding Applicant - IQVIA Ltd ( UK )
Bhagya Chengat - Collaborator - IQVIA Ltd ( UK )
Jessica Lundbom - Collaborator - IQVIA Ltd ( UK )
Louise Raiteri - Collaborator - IQVIA Ltd ( UK )
Sarah Lay-Flurrie - Collaborator - IQVIA Ltd ( UK )
Saskia Hagenaars - Collaborator - IQVIA Ltd ( UK )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation