Supplements Update on the Diagnosis and Treatment of Gout
Clinical, Humanistic, and Economic Outcomes of Gout
Gout is a low prevalence disease not often considered by managed care organizations with regard to cost management. Understanding the development of the disease and its potential long-term, high-cost consequences can lead to appropriate treatment strategies and cost-management opportunities that can improve patient outcomes and potentially lower the overall cost of treatment of patients with gout in a managed care organization. The acute and chronic nature of the disease is best managed up front to avoid negative long-term effects. Adherence to medications can also impact the manifestation of the disease.
(Am J Manag Care. 2005;11:S459-S464)
Gout is a disease of relatively low prevalence in relation to the disease categories most often considered in managed care populations. Despite a relatively low prevalence, however, the impact of this disease on patients, health plans, and their employer clients can be substantial. As the disease progresses, clinical outcomes may be severe, with marked impairment of activities of daily living and ability to work. Management of this disease can be complex and long-term, leading to substantial direct costs to a health plan.
The purpose of this article is to provide a review of the prevalence of gout, how the disease presents to the healthcare provider, and management of the disease during its progression through acute and chronic phases. After a review of clinical outcomes, the humanistic impact of gout will be presented along with the direct and indirect costs associated with treating this disease. This information should assist health plans in overall management of the disease for their patients and clients.
Disease Background and Prevalence
Gout results from an inflammatory response caused by hyperuricemia and the resulting deposition of monosodium urate monohydrate crystals in the articular cartilage and synovial membrane. Patients experience acute attacks of arthritis in 1 or more of the extremities, and the majority of patients will have another attack within 2 years of the previous one.1 Crystal deposition is also associated with urinary tract stones. Left untreated, patients may develop crystal aggregates, which can destroy cartilage and bone and lead to organ dysfunction, particularly renal impairment.2
Although age, body mass index (BMI), hypertension, cholesterol level, and alcohol intake are all associated with the development of gout, the incidence of the disease most closely correlates with elevated uric acid levels. In the Normative Aging Study, 2046 healthy and asymptomatic men were followed for 14.9 years and evaluated for serum urate (SU) levels and first episodes of gouty arthritis. The annual incidence of gouty arthritis was 4.9% for those with prior SU levels of 9.0 mg/dL compared with 0.5% among patients with urate levels between 7.0 and 8.9 mg/dL, and only 0.1% among those having urate levels >7.0 mg/dL. Also, those with urate levels of 9.0 mg/dL showed a cumulative incidence of gouty arthritis of 22% after 5 years.3
The National Arthritis Data Workgroup reviewed self-reported gout data and estimated the prevalence of gout to be about 8.4 cases per 1000 individuals, correlating to 2.1 million US patients with the disease. The incidence of gout increases with age and is 3.8 per 1000 individuals among those aged 18 to 44 years, 16.8 per 1000 among those aged 45 to 64, and 29.0 per 1000 for those aged 65 and older (Table). Gout prevalence is higher in men than in women and higher in blacks than whites.1 Left untreated, 75% of patients will develop severe and crippling tophaceous gout within 20 years of the initial attack of gouty arthritis.4 With adequate treatment, however, only 5% of patients will develop tophaceous gout during this time.5
Recent data show that the prevalence of gout and hyperuricemia in a managed care claims database increased by approximately 2 cases per 1000 patients during the 10-year period between 1990 and 1999, and this increase occurred primarily among those older than age 65.6
Delayed or erroneous diagnoses led to ineffective treatment and persistent joint pain in more than one quarter of gout patients in a hospital-based rheumatology practice. Erroneous diagnoses included cellulitis, phlebitis, septic arthritis, venous thrombosis, and osteomyelitis. A correct diagnosis can eliminate unnecessary medications and hasten pain relief.7
Despite this incidence of misdiagnoses, a British survey of general practitioners showed that 86.3% felt confident in their ability to manage gout without advice from a specialist. Nonetheless, 32.1% reported that they were likely to refer patients with gout to a rheumatologist.8
Potential Causes and Associations
Gout has been associated with a spectrum of causes, including renal impairment, cardiovascular disease, weight change, diet, and substance use. The articular symptoms are often the first manifestation of a reversible metabolic or endocrine disorder.9 Renal impairment is observed in 10% to 15% of patients with gout and is manifested as urate and uric acid nephropathy or nephrolithiasis, potentially resulting in renal failure.9
Hyperuricemia and gout frequently coexist with cardiovascular disorders, and insulin resistance has been proposed as the pathogenic link explaining this association. Hypertension, diuretic use, and obesity are significantly more common among patients with gout than in the general population, and gout often accompanies other traditional coronary artery disease risk factors, such as diabetes and hyperlipidemia. Although gout has not been shown to be an independent risk factor for heart disease, it may be prudent to assess cardiovascular risk in these patients.10,11
Researchers have found that weight gain and increased adiposity are strong risk factors for gout and that weight loss is protective against the disease. The relative risk of gout is 1.95 in men with a BMI of 25 to 29.9 kg/m2, 2.33 for those with a BMI of 30 to 34.9 kg/m2, and 2.97 for obese men with a BMI of ³35 kg/m2 (P for trend <.001).10
Dietary restriction has been shown to reduce serum uric acid levels and the frequency of gouty attacks.12 In contrast, a diet including increased amounts of purine-rich foods, meat, and alcoholic beverages is associated with increased gouty attacks. In one study, beer consumption showed the strongest independent association with increased gout incidence, spirit consumption showed a significant association, but wine consumption was not related to increased incidence.13 Other research suggests that consumption of vegetable protein may be protective against gout.14
Although adherence to dietary restrictions and reduced alcohol consumption are helpful, pharmacologic therapy remains the mainstay of gout treatment. Urate-lowering therapy is generally cost effective for any patient with more than 2 gouty flares annually, and the choice of urate-lowering agent should be individualized to the patient. In addition, nonsteroidal anti-inflammatory drugs (NSAIDs) or other anti-inflammatory agents may be used to reduce symptoms and disability.
An acute gouty attack is the primary clinical manifestation. Attacks are usually monoarticular with inflammation of the first metatarsophalangeal joint. Although less common, gouty attacks may spread to other joints, including the instep, forefoot, ankle, knee, wrist, and fingers. Symptoms may be self-limiting if untreated, but 60% of patients have a second attack within 1 year, and 78% have a second attack within 2 years. Only 7% of patients do not experience a second gouty attack in a 10-year period.15 Chronic gouty arthritis with persistent pain and joint involvement occurs in <5% of patients with gout.16 Acute uric acid nephropathy may also occur.
After 10 to 20 years of inadequately treated gouty attacks, chronic tophaceous gout may develop.16 The percentage of patients with gout who develop tophaceous gout has decreased significantly, however, from 14% in 1949 to 11% in 1959, 8% in 1969, and 3% in 1972, according to a retrospective study.5 The authors attributed the decrease to enhanced diagnostic methods and the development of uricosuric drugs along with the increasing use of colchicine for gout between the 1960s and 1972. Tophi can cause joint deformity, damage surrounding soft tissue, and lead to joint destruction as well as chronic, persistent pain and nerve compression syndromes.17 In rare cases, tophaceous gout of the spine develops with back pain and fever that make it difficult to distinguish from epidural infection.18
Hyperuricemia control is superior to selfmedication alone in improving the prognosis of chronic gout, decreasing comorbidity, and reducing mortality. In fact, self-medication alone may cause significant adverse effects, such as gastrointestinal (GI) complications from long-term use of NSAIDs.19 The overall incidence of upper GI bleeding and upper GI bleeding resulting in hospitalization was 2.9 and 1.0 per 1000 indomethacin-exposed patients in one study.20 Each incident exacerbated gout and decreased patient comfort.
Patients with gout exhibit poorer social functioning than those with hypertension, angina, diabetes, or lower urinary tract symptoms, as measured by the quality-of-life Short Form-36. Men aged 55 to 64 years with gout scored worse in terms of physical functioning, general health perception, vitality, role limitations due to emotional problems, and mental health than those with other disease states.21 However, in another study, patients with gout scored lower, indicating better functioning, on the Health Assessment Questionnaire (0.44) compared with patients with rheumatoid arthritis (0.87) and polymyalgia rheumatica (0.68).22
Treatment nonadherence contributes to decreased quality of life in patients with gout. A recent analysis of 9482 managed care enrollees with gout revealed that patients were adherent with allopurinol therapy for an average of 56% of the treatment period, but were nonadherent 44% of the time. Also, 65.9% of patients filled 1 allopurinol prescription and 10.4% discontinued use after the first prescription. Only 18% of patients were adherent throughout the study period, and 13.7% never achieved adherence with therapy.2 Nonadherence with urate-lowering drugs allows the SU concentration to increase, and this eventually may lead to increased frequency of future gouty attacks.23
Gout is associated with significantly decreased productivity, a high economic burden, and a managed care burden. The annual direct burden of illness for new cases of acute gout among men in the United States is estimated at $27.4 million. Data on gout in women are lacking, and they were not included in this estimate.24 Exact indirect costs associated with gout are difficult to determine. However, gout accounted for 37 million days of restricted activity from 1979 to 1981 in the United States, with 9.2% of all men with gout reporting limitations in performing major activities.25
Patients with acute gouty arthritis attacks miss an average of 3 to 5 days of work annually, and it is likely that individual productivity losses are made up on return to work or at the worksite during the absence.20 This loss can translate to thousands of dollars per employee per year to an employer for days paid with no labor in return.26