Gout is one of the most common causes of arthritis in patients over 40, its prevalence ranges from 0.5% to 5% of the general population.1,2 It is a disease characterized by the presence of inflammatory episodes, usually monoarticular and recurrent, often intense and self-limited.3,4 Clinical manifestations of gout occur in three phases: (a) acute attacks, (b) intercrisis periods (tophi are a late symptom of the disease), and (c) chronic arthropathy (multiple and/or persistent attacks).5–8

Available studies show that in patients with obesity, hypertension and/or diabetes (high cardiovascular risk), serum urate levels can be considered as a marker of inflammation, ischemia and oxidative stress of the cardiovascular system.9,10 The association between gout and the metabolic syndrome (MS) is well documented. Studies show that serum urate levels increase as the number of MS components increase, even when set against confounding factors such as age, gender, creatinine clearance, diuretic use and alcohol consumption.11–13 Overall, the prevalence of MS according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III)14 ranges from 19% to 71%.

The available evidence regarding the use of resources and costs is limited.15,16 In the US it is estimated that the annual direct costs for treating new cases of gout in men is approximately $ 27.4 million.17 In the few studies reviewed there is a great variability in the methodology used to calculate these resources; moreover, they have been performed in very different groups of patients (cohort of employees, the elderly, etc.),18–21 circumstances that affect the comparability and external validity of the results. Given this scenario, and given the lack of data available in our country regarding the follow up of patients with gout in routine clinical practice situations, the performance of this type of study may be relevant. The objective of the study was to determine the use of resources and the economic impact (health and non-health costs) of patients with gout in a Spanish population setting with a follow-up period of 2 years.

From an initial screening of 96206 subjects ≥18 years assigned to the centers, we enrolled 3130 patients with gout. The overall prevalence was 3.3% (95% CI: 2.7%–3.9%). The estimated cumulative incidence rate was 1.1 new cases/1000 inhabitants/year. Regarding study groups, 2142 (68.4%) had 1–2 acute attacks and 988 (31.6%) 3 or more recurrences, P<.001. The mean±SD age was 55.8±12.2 years and 81.1% were male. Of all patients, 43.6% were hypertensive, 43.1% obese and 40.5% dyslipidemic. The prevalence of MS was 28.8% (95% CI: 27.2%–30.4%).

Table 2 describes the general characteristics of the series and comorbidities associated with gout in patients according to the 2 study groups. Subjects with ≥3 acute attacks/relapses showed a higher mean age (57.2 vs 55.2 years, P<.001), and a higher proportion of males (84.1% vs 79.7%, P=.004). These subjects had a higher proportion of comorbidities: BUR (3.1 vs 2.9, P<.001) and Charlson index (1.1 vs 0.9, P<.001). In the corrected logistic regression model, subjects with ≥3 acute attacks/relapses were associated with MS (odds ratio [OR]=6.2, 95% CI: 4.6–8.3), obesity (OR=2.1, 95% CI: 1.7–2.5) and hypertension (OR=1.6, 95% CI: 1.3–1.9), P<.001. MS had a moderate linear correlation with the number of acute attacks (r=0.517), years of disease progression (r=0.321) and initial levels of uric acid (r=0.278), P<.001. Baseline characteristics of gouty arthropathy are detailed in Table 3, 89.1% of subjects had hyperuricemia and 84.7% of the cases were from PC. Subjects with ≥3 acute attacks/relapses showed increased monitoring in the rheumatology clinics (3.6% vs 0.8%, P<.001). Notably, only 16.9% of patients had a definite diagnosis of gout (displaying monosodium urate crystals under a microscope). Regarding the study groups, in subjects with ≥3 acute attacks/recurrence was 29.0% vs 11.3%, P<.001.

The gross prospective and adjusted cost model (up to 24 months) associated with gout according to the study groups is described in Table 4. The total cost of the patients included in the study amounted to 7 million euros, of which 96.9% were direct health costs and 3.1% non-healthcare costs (lost productivity), with an average/€ 2228.6 total unit. For groups, the total costs (health, non-health) of subjects with 1–2 attacks of gout were lower compared with those with ≥3 attacks (€ 2028.6 vs € 2662.2). The percentage distribution of the cost is 90.8% in PC and 6.2% in specialized care, of these, 23.5% of visits occurred in PC and 57.7% in drug prescription. In the corrected multivariate model, costs were lower in the group with 1–2 attacks, especially total healthcare costs (€ 2101.5 vs € 2517.4, P<.001) and in PC (1987.6 € vs € 2331.3, P<.001). The average/unit of the total costs per patient was € 2130.6 vs € 2605.4 respectively (P<.001). In all the cost components results were higher in the group with ≥3 attacks. During the study period, patients with ≥3 acute attacks/relapses showed a higher average number of job loss (2.3 vs 1.2, P<.006) and days off work (0.6 vs 2.6 days, P<.001).

The subgroup of diabetic patients (No.=641, 20.5%, 95% CI: 19.1%–21.9%) compared to non-diabetic ones, had a higher average unit total cost (€ 3124.8 vs € 1997.8, P<.001); these patients were older (61.9 vs 54.2 years, P=.001), had a higher disease burden (3.1 vs 2.8 BUR, P<.001) and frequency of MS (63.2% vs 20.1%, P<.001).

The overall results of the study show a prevalence of 3.3% for gout, with a grater male predominance and with 1–2 acute attacks. These features are similar to most of the population-wide studies reviewed.3,4 Although it should be noted that the natural history of the disease may hinder its diagnosis, especially in primary care and in the emergency department, where the presence of a joint acute attack may mimic other disease entities making for a difficult differential diagnosis.3,6,8 According to the NCEP,14 the prevalence of MS was 28.8%, highlighting its association with obesity, hypertension and high baseline levels of uric acid. Our results are similar to data from other studies reviewed.7,8,11–13 It is worth considering that in our country the prevalence of MS and its association with gout may be higher. Some authors put the figures at around 50% in patients over 60% and 35% in patients with gout in the general population.29

In the study, the average/unit cost was € 2228.6. The average corrected model/unit total costs per patient was € 2130.6 (1–2 attacks) vs € 2605.4 (≥3 attacks). In all components result costs were higher in the group with ≥3 attacks and the subgroup of diabetic patients. In this aspect, Brook et al.,21 demonstrated that the total annual cost in a cohort of employees with gout was $ 6870, two times higher than patients without gout, noting that only 1% of employees with gout generated the 20% of the costs. Wu et al.,18 in an excellent study done in elderly patients, related the serum uric acid levels with the cost of patients with gout as being $ 2555. In the study by Mould-Quevedo et al.,19 on the main inflammatory rheumatic diseases from the patient's perspective in Mexico, the cost/year was $ 1006, mostly in outpatient costs. Our results are in line with those reported by Wu et al.,18 where the methodology was similar to that described in this paper, even when bearing in mind that their patients were older and probably with greater comorbidity. The other two studies mentioned previously (Wu et al.18 and Mould-Quevedo et al.19) are difficult to compare because they are made with older patients and also use different methodologies. All studies are coincident on the weight of the ambulatory costs. In our study, 96.9% were direct health costs and the increased costs were due to follow-up visits and medication. In this regard, increased monitoring of these patients in primary care could reduce costs related to the disease, although undoubtedly the associated morbidity, lack of compliance and possible predisposing factors may affect the use of resources and the cost of these30 patients.

It is important to note the scarce costs related to lost productivity (sick leave) generated by gout. One possible explanation is that we used a conservative information source (the minimum wage instead of average wage cost, which already in itself is a limitation of the study); it is also possible that temporary job loss was seen (early treatment or decompensation) and not registered by the insurers. The available evidence in this area regarding costs would be consistent with Ferraz20 and Joish,31 who show that patients with acute attacks of gouty arthritis lose an average of 3–5 days of work per year, causing significant economic losses to labor productivity that in some cases is a little less quantified. Although, in general, patients with 1–2 attacks are younger and therefore have a lower frequency than most of the associated disease, it may be this which determines the lowest cost of the disease in these patients.

Possible study limitations affect the categorization of the disease, the potential bias of patient classification (due to excess) and operating costs attributable to the information system developed. Therefore, in this paper we show the limitations of retrospective studies, such as underreported data or the possible variability of professionals and patients due to the observational design. Furthermore, the number of acute attacks treated may be compromised because of possible self-medication by patients. The study details the use of resources and the costs associated with gouty arthritis patients in a clinical practice situation. However, note that without adequate standardization of methodologies not only in terms of patient characteristics, but also the number and size of the variables studied, the results should be interpreted with caution forcing us to be cautious regarding the external results validity.

Future research studies call for the availability of cost/effectiveness and efficiency of diagnosis and treatment, in addition to replicating the study in other healthcare organizations. Moreover, the inflammatory property of crystals is not yet fully elucidated and may be linked to the ability to bind immunoglobulins, complement and lipids. It takes long-term clinical trials to test the hypothesis that uric acid lowering therapy can reduce cardiovascular risk in these patients. No guidelines have been established, derived from clinical trials, for the treatment of acute joint inflammation. The success of interventions for patients with chronic diseases such as gout should be based on multidisciplinary teams that promote effective care in which patients are highly engaged in their own care. Undoubtedly, the diagnosis and treatment of gout should require greater intervention strategy and be monitored by health professionals. In conclusion, gout is associated with substantial morbidity, MS and healthcare resource consumption. This study provides useful data on the cost of gout in Spain. The greatest costs are owed to the follow up of ambulatory patients.

A. Sicras and R. Navarro conducted the literature search, extracted the data, performed the analysis and interpretation of the initial results. All authors contributed ideas, interpreted findings and reviewed drafts of the manuscript. All authors approved the final version of the article. A. Sicras is responsible for the study.

The authors have no conflict of interest to make.