Epidemiology of gout, its treatment and comorbidities - a prospective cohort study using data from Clinical Practice Research Datalink (CPRD)

Study type
Protocol
Date of Approval
Study reference ID
20_000233
Lay Summary

Gout is a common arthritis characterised by the presence of needle-shaped urate crystals inside the joints. Once shed, they cause a flare characterised by abrupt onset of pain, tenderness, and swelling. A study using data from the CPRD reported that the prevalence of gout in the UK increased dramatically between the mid-1990s and 2010, and that only one in three patients with gout were prescribed urate lowering medicine e.g. allopurinol in this period. Studies from other countries report that the prevalence of gout has not changed between 2010 and 2020. Currently, it is not known if the prevalence of gout has stabilised in the UK in recent years or if coverage with allopurinol has improved after the latest recommendations by the British Society of Rheumatology published in 2017. Additionally, gout associates with heart attack, stroke and deep vein thrombosis. However, it is not known if the risk of these illnesses is increased in the period soon after a gout flare.
The purpose of this study is to assess whether the number of people with gout has increased in the UK in recent years, and to find out if more people with gout are being prescribed medicines such as allopurinol. We will also find out whether gout flares associate with heart attack, stroke or blood-clots in the veins or lungs in the short-term. We will find out whether people with early gout or consulting due to gout for the first time are at an increased risk of heart attack and stroke.

Technical Summary

Objectives: To examine the [1] temporal trend in incidence and prevalence of gout between 1997-2021, [2] temporal trend in all-cause mortality and prevalence of urate lowering treatment (ULT) prescription, ULT prescription achieving serum urate treatment target, in patients with gout between 1997-2021, [3] association between gout flares and acute myocardial infarction, stroke, venous thromboembolism.
Design: prospective cohort study with nested cross-sectional and case-control studies.
Study period: 01/01/1997– 30/09/2021.
Data sources: CPRD, Hospital Episode Statistics, Office National Statistics.
Methods: We will calculate the point prevalence of gout, and ULT prescription in people with gout on the 1st July between 1997 and 2021. Participants in receipt of ULT prescription(s) in the 60 days preceding the 1st of July will be classified as prescribed ULT. The latest serum urate before 1st July of each year will be used to define whether the serum urate is below treatment target or not for those on ULT. Similarly, annual incidence of gout between 1997 and 2021, and mortality rate of gout cases incident in each calendar year between 1997 and 2021 will be calculated. Join Point regression will be used to examine the temporal trends. The association between acute myocardial infarction, stroke, venous thromboembolism, and gout will be assessed using nested case-control study design. The nested case-control study will include controls that are age, sex and duration of registration in CPRD matched to cases, and adjusted for covariates including demographic factors, lifestyle factors, ULT, and comorbidities. Three nested case control studies will be performed, one for each outcome of interest. Patients consulting for gout for the first time will be followed-up to explore if those consulting with gout flares are at higher risk of cardiovascular events. Conditional logistic regression and Cox-regression will be used. Adjusted OR, HR and 95% confidence intervals (CIs) will be calculated.

Health Outcomes to be Measured

• Gout – incident and prevalent
• Urate lowering treatment prescription
• Urate lowering treatment achieving serum urate treatment target (serum urate less than 300 micromol/L)
• Death
• Acute myocardial infarction
• Acute stroke
• Venous thromboembolism – defined as either deep vein thrombosis or pulmonary embolism,

Collaborators

Abhishek Abhishek - Chief Investigator - University of Nottingham
dalia Elmelegy - Corresponding Applicant - Nottingham University Hospitals
Anthony Avery - Collaborator - University of Nottingham
Edoardo Cipolletta - Collaborator - University of Nottingham
Georgina Nakafero - Collaborator - University of Nottingham
Laila Tata - Collaborator - University of Nottingham
Mamas Mamas - Collaborator - Keele University

Former Collaborators

Edoardo Cipolletta - Collaborator - University of Nottingham

Linkages

HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation