Population-based study on the epidemiology of gout

Pharmacoepidemiology enables researchers to assess the effects of drugs on outcomes, such as diseases, in large study populations. Furthermore, pharmacoepidemiology is gaining importance in the premarketing phase of the drug development process to provide information on the natural history of the disease the respective drug is being tested for.
Gout is a common, excruciatingly painful, long-known and widely spread inflammatory arthritis characterized by increased serum uric acid levels, and uric acid crystals in the joints (typically in the metatarsophalangeal joint, called podagra. Even though the disease has been long-known and affects about 1.4% to 2.5% of the United Kingdom (UK) population, evidence on many risk factors is lacking. Studies that closely describe the affected population and strengthen existing evidence on risk factors such as drug use are needed to improve treatment and care of affected patients.
The aim of this thesis was to increase the knowledge of gout by providing new information and complementing existing data, and by precisely describing the epidemiology of gout and demographic characteristics, comorbidities, and comedication of the affected population. Furthermore, the goal was to assess the impact of long-known and accepted risk factors in a population-based setting.
The gout project consisted of an epidemiological cohort study, a nested case-control study, and three case-control studies, using data from the Clinical Practice Research Datalink (CPRD). The CPRD is a UK-based general practitioner database containing primary-care records directly entered by general practitioners who do not have any study hypothesis in mind when they record the data. The CPRD population is representative of the UK population in terms of age, sex, geographic distribution, and annual turnover rate. The CPRD is a very useful tool to conduct pharmacoepidemiological research due to its large size, the population-based character of the data, and the opportunity for researchers to gain access to original medical records. However, data on some important confounders such as dietary habits are missing.
All case-control populations of the different gout projects were matched on age, sex, general practice, index date, and history on the CPRD. The overall incidence rate of diagnosed gout in the UK per 10,000 person-years (PYs) was 18.0 (95% CI 17.9-18.1), 29.0 (95% CI 28.8-29.2) in men, and 8.6 (95% CI 8.5-8.8) in women; we further stratified by age, calendar time, region, and seasonality. The nested case-control part of the first project described the study population in terms of demographic characteristics, comorbidities, and comedication. The second project assessed the association between different diuretic drug classes and incident gout. Current use of loop diuretics, thiazide diuretics, and thiazide-like diuretics was associated with a substantially increased risk of incident gout. In the third project, the association between different antidiabetic drug classes, diabetes duration, and diabetes severity and the risk of incident gout was investigated. Increasing glycosylated haemoglobin (A1C) levels were associated with a markedly decreased risk of incident gout in patients with type 2 diabetes mellitus. Neither use of insulin, metformin, nor sulfonylureas was associated with an altered risk of incident gout. The fourth project assessed the association of hormone replacement therapy with gout, and the effect of timing, duration, and route of administration. Current use of oral opposed oestrogens, but not unopposed oestrogens, was associated with a decreased risk of incident gout in patients without renal failure and was more pronounced in patients with hypertension. The observed risk decrease for gout in users of opposed oestrogens may be explained by the progesterone rather than the oestrogen component.
In summary, these large observational studies of this thesis analysed existing hypotheses and contributed to the evidence of different risk factors for gout such as diuretic drug classes, antidiabetic drugs, diabetes duration and severity, and hormone replacement therapy. Furthermore, several interesting ideas developed in the context of this thesis might be studied in association with gout within the CPRD in near future, to further increase evidence on risk factors associated with the disease, and to improve patient care.