Current state and prospects of gout treatment in Korea

Effective management of gout includes the following: appropriate control of gout flares; lifestyle modifications; management of comorbidities; and long-term urate-lowering therapy (ULT) to prevent subsequent gout flares, structural joint damage, and shortening of life expectancy. In addition to traditional treatments for gout, novel therapies have been introduced in recent years. Indeed, new recommendations for the management of gout have been proposed by various international societies. Although effective and safe medications to treat gout have been available, management of the disease has continued to be suboptimal, with poor patient adherence to ULT and failure to reach serum urate target. This review outlines recent progress in gout management, mainly based on the latest published guidelines, and specifically provides an update on efficient strategies for implementing treatment, efficacy and safety of specific medications for gout, and cardiovascular outcomes of ULT. In particular, we reviewed gout management approaches that can be applied to a Korean population.

Patient Perspectives and Preferences Regarding Gout and Gout Management:Impact on Adherence

Background@#Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). @*Methods@#A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. @*Results@#Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). @*Conclusion@#Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Patient Perspectives and Preferences Regarding Gout and Gout Management:Impact on Adherence

Background@#Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). @*Methods@#A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. @*Results@#Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). @*Conclusion@#Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

What is the Best Choice for Urate-lowering Therapy for Korean?

Gout is one of the most common forms of acute inflammatory arthritis caused by long-standing hyperuricemia. Various clinical and epidemiological studies have demonstrated that uric acid, which is strongly associated with the pathogenesis of gout, is closely related with increased cardiovascular (CV) risk. Thus, properly controlling uric acid levels within its physiological level using urate-lowering therapy has been hypothesized to improve CV outcomes. Recently, however, on the basis of the results of the largest prospective, the double-blind, randomized controlled trial, entitled “the Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES),” has aroused the possibility of increased CV-related and all-cause mortality in patients receiving febuxostat. Largely on the basis of this unpredicted result, the US and Korea Food and Drug Administration issued a public safety alert concerning the high risk of CV death with the use of febuxostat in February 2019. This unexpected announcement left many rheumatologists confused when they decide the first-line urate-lowering drug in Korea. In this review, we searched for previous studies on uric acid and increased risk of CV disease. In addition, we will introduce various interpretations of the results of the CARES trial and discuss the best choice of urate-lowering therapy for Korean.

The Utility of the Random Urine Uric Acid-to-Creatinine Ratio for Patients with Gout Who Need Uricosuric Agents: Retrospective Cross-Sectional Study

Background@#The 24-hour uric acid excretion measurement is important in assessing disease status and helping to select the appropriate uric acid-lowering agent for patients with gout, however, it is inconvenient. The authors investigated the efficacy of the random urine uric acid-to-creatinine (UA/CR) ratio to screen the patients who under-secreted 24-hour urine uric acid. @*Methods@#This was a retrospective cross-sectional study. Ninety patients with gout, without undergoing uric acid-lowering treatment were enrolled. Twenty-four-hour urine and random urine samples were obtained on the same day. Six hundred mg of uric acid in the 24-hour urine sample was used as a standard for distinguishing between over and under-excretion groups. @*Results@#The random urinary UA/CR ratio showed positive correlation with 24-hour urine uric acid excretion (γ = 0.398, P < 0.001). All the patients with the random UA/CR less than 0.2 excreted less than 600 mg uric acid in 24-hour urine collection. When the random urine UA/CR ratio < 0.2 was regarded as a positive result, the positive predictive value, negative predictive value, sensitivity, and specificity in the uric acid under-excretion were 100% (8 of 8), 64.6% (53 of 82), 21.6% (8 of 37), and 100% (53 of 53), respectively. @*Conclusion@#There is a moderate positive correlation between the random urinary UA/CR ratio and 24-hour urine uric acid excretion, so that UA/CR ratio may not be a good predictor of 24-hour urine uric acid excretion. However, the random urine UA/CR ratio 0.2 can be a useful predictor to screen the gouty patients who need to be treated with uricosuric drugs.

Trends of Gout Prevalence in South Korea Based on Medical Utilization: A National Health Insurance Service Database (2002∼2015)

Objective@#. Although gout is the most common form of inflammatory arthritis, data on gout prevalence and management are sparse, especially in Korean populations. This study reevaluated the most recent prevalence and incidence of gout values in Korean people to update the findings from our previous study in 2011. @*Methods@#. We used the National Health Insurance Service-National Health Information Database (NHIS-NHID) to identify patients diagnosed with gout in South Korea during 2002∼2015. We selected patients with gout as principal diagnosis or 1st∼4th additional diagnosis. @*Results@#. The prevalence of gout increased 5.17-fold, from 0.39% in 2002 to 2.01% in 2015. This increase occurred in all age groups, but was stronger in those aged 80 years or older, with a 13.1-fold increase from 2002 to 2015. The prevalence of gout increased in all regions of South Korea. The prevalence of the disease was also related to income levels: in 2015, medical insurance subscribers with the highest income were twice more likely to have gout than those in the lowest income bracket. By contrast, the prevalence of gout in medical benefit recipients was 5.58- and 5.25-times higher than that of the general population and of those in the highest income bracket, respectively. @*Conclusion@#. The prevalence of gout has increased rapidly, although the degree of increase varied according to sex, age, region, and income group. This study sheds some light on the current prevalence of gout among national insurance subscribers in Korea, and will help educate patients and medical staff on the management of gout.

The Utility of the Random Urine Uric Acid-to-Creatinine Ratio for Patients with Gout Who Need Uricosuric Agents: Retrospective Cross-Sectional Study

Background@#The 24-hour uric acid excretion measurement is important in assessing disease status and helping to select the appropriate uric acid-lowering agent for patients with gout, however, it is inconvenient. The authors investigated the efficacy of the random urine uric acid-to-creatinine (UA/CR) ratio to screen the patients who under-secreted 24-hour urine uric acid. @*Methods@#This was a retrospective cross-sectional study. Ninety patients with gout, without undergoing uric acid-lowering treatment were enrolled. Twenty-four-hour urine and random urine samples were obtained on the same day. Six hundred mg of uric acid in the 24-hour urine sample was used as a standard for distinguishing between over and under-excretion groups. @*Results@#The random urinary UA/CR ratio showed positive correlation with 24-hour urine uric acid excretion (γ = 0.398, P < 0.001). All the patients with the random UA/CR less than 0.2 excreted less than 600 mg uric acid in 24-hour urine collection. When the random urine UA/CR ratio < 0.2 was regarded as a positive result, the positive predictive value, negative predictive value, sensitivity, and specificity in the uric acid under-excretion were 100% (8 of 8), 64.6% (53 of 82), 21.6% (8 of 37), and 100% (53 of 53), respectively. @*Conclusion@#There is a moderate positive correlation between the random urinary UA/CR ratio and 24-hour urine uric acid excretion, so that UA/CR ratio may not be a good predictor of 24-hour urine uric acid excretion. However, the random urine UA/CR ratio 0.2 can be a useful predictor to screen the gouty patients who need to be treated with uricosuric drugs.

Seasonal Variations and Associated Factors of Gout Attacks: a Prospective Multicenter Study in Korea

Background@#We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. @*Methods@#We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. @*Results@#Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; −0.9%, fall; −1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. @*Conclusion@#In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.

Simplified disease activity changes in real-world practice: a nationwide observational study of seropositive rheumatoid arthritis patients with moderate-to-high disease activity

The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Increased Carotid Intima-Media Thickness (IMT) in Hyperuricemic Individuals May Be Explained by Hyperhomocysteinemia Associated with Renal Dysfunction: a Cross-Sectional Study

BACKGROUND: Both hyperuricemia and hyperhomocysteinemia are known as main risk factors of cardiovascular diseases. There has been, however, no report on the relationship between carotid intima-media thickness (IMT) and homocysteine (Hcy) in hyperuricemic patients. This study aimed to investigate how hyperuricemia is associated with increased carotid IMT with a focus on hyperhomocysteinemia. METHODS: This cross-sectional study included 1,222 patients who visited the Chung-Ang University Hospital Health Promotion Center from January 2013 to December 2015. The serum Hcy levels were estimated with a competitive immunoassay using the direct chemiluminescence method. The carotid IMT was measured by B-mode carotid ultrasonography. The definition of hyperuricemia was a serum uric acid level > 7.0 mg/dL for men or > 5.6 mg/dL for women, and hyperhomocysteinemia was defined as serum levels > 15 μmol/L. RESULTS: The hyperuricemic patients showed significantly higher serum Hcy levels and lower estimated glomerular filtration rate (eGFR) than did normouricemic patients (13.39 ± 4.42 vs. 11.69 ± 3.65 μmol/L, P < 0.001; 85.16 ± 19.18 vs. 96.14 ± 16.63, P < 0.001, respectively). Serum Hcy level (odds ratio [OR], 1.050; 95% confidence interval [CI], 1.009–1.092) and fasting glucose level (OR, 1.018; 95% CI, 1.011–1.026) were independent risk factors for carotid plaque. In patients with hyperuricemia, the serum Hcy levels correlated with the eGFR (γ = −0.478, P < 0.001). The carotid IMT correlated with serum Hcy levels and eGFR (γ = 0.196, P = 0.008; γ = − 0.297, P < 0.001, respectively) but not with the serum lipid profile. CONCLUSION: These results suggest that renal function impairment in hyperuricemic patients may worsen carotid IMT by increasing serum Hcy levels.

New Classification Criteria and Guideline for Management of Gout / 대한내과학회지

Gout is a chronic systemic metabolic disease characterized by recurrent attacks of inflammatory arthritis resulting from the precipitation of monosodium urate crystals, which has various clinical and pathological manifestations. The disease is associated with multiple comorbidities, an impaired quality of life, and a heavy economic burden. The incidence and prevalence of gout is increasing in many developed and developing countries, as in Korea. Gout is diagnosed by confirming monosodium urate crystals in the synovial fluid or affected tissue. If crystal documentation is unavailable, new gout classification criteria presented by the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) in 2015 can be applied. There are many guidelines for managing gout published in the United States, Japan, and Europe. However, there are no guidelines for the tailored management of gout for Korean patients. This review describes a new classification for the diagnosis of gout and management guidelines.

Rivaroxaban for Thromboprophylaxis in Patients with Antiphospholipid Syndrome

The main treatment for Antiphospholipid syndrome (APS) is long-term anticoagulation with an oral vitamin K antagonist, although these are associated with numerous problems. Rivaroxaban is a direct anti-factor Xa inhibitor, with a predictable anticoagulant effect at fixed doses. There are limited reports of rivaroxaban use in APS. We present four cases of patients with APS who received rivaroxaban treatment for six months without thrombosis recurrence or bleeding. Three of the patients received rivaroxaban as initial therapy. In the systematic review, only five patients were treated with rivaroxaban as a thromboprophylaxis. Of the 71 cases of rivaroxaban use including our study, there were seven cases (9.9%) of thrombosis recurrence and two reports of bleeding. The efficacy of rivaroxaban in APS patients was at least equal to warfarin therapy. This report and systematic review suggest that rivaroxaban can be considered cautiously as a thromboprophylactic or alternative therapy for warfarin in patients with APS.

Rising a Novel Weapon in the War against Gout and Hyperuricemia

No abstract available.

Recent advances in management of gout

Gout, which is caused by the deposition of monosodium urate crystals in synovial fluid and other tissues, is the most common inflammatory rheumatic disease in men, at least in the Western world, and is increasing in prevalence worldwide. In addition to extremely painful recurrent acute and chronic arthritis, gout is associated with chronic kidney diseases and metabolic syndrome, including dyslipidemia, hypertension, hyperglycemia, and obesity. Thus it has an impact on morbidity and premature mortality. For the proper management of gout, definite diagnosis should come first. Management plans for the treatment of gout have to be designed to meet the requirements of each individual patient and to control both gout and its associated disorders. The goals of treatment for gout are fast pain relief and the prevention of future gout attacks and long-term complications, such as joint destruction and other comorbidities. In this article, recent advanced non-pharmacologic and pharmacologic management strategies for gout and hyperuricemia will be described.

Serum Procalcitonin as a Useful Serologic Marker for Differential Diagnosis between Acute Gouty Attack and Bacterial Infection

PURPOSE: Patients with gout are similar to those with bacterial infection in terms of the nature of inflammation. Herein we compared the differences in procalcitonin (PCT) levels between these two inflammatory conditions and evaluated the ability of serum PCT to function as a clinical marker for differential diagnosis between acute gouty attack and bacterial infection. MATERIALS AND METHODS: Serum samples were obtained from 67 patients with acute gouty arthritis and 90 age-matched patients with bacterial infection. Serum PCT levels were measured with an enzyme-linked fluorescent assay. RESULTS: Serum PCT levels in patients with acute gouty arthritis were significantly lower than those in patients with bacterial infection (0.096±0.105 ng/mL vs. 4.94±13.763 ng/mL, p=0.001). However, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels showed no significant differences between the two groups. To assess the ability of PCT to discriminate between acute gouty arthritis and bacterial infection, the areas under the curves (AUCs) of serum PCT, uric acid, and CRP were 0.857 [95% confidence interval (CI), 0.798-0.917, p<0.001], 0.808 (95% CI, 0.738-0.878, p<0.001), and 0.638 (95% CI, 0.544-0.731, p=0.005), respectively. There were no significant differences in ESR and white blood cell counts between these two conditions. With a cut-off value of 0.095 ng/mL, the sums of sensitivity and specificity of PCT were the highest (81.0% and 80.6%, respectively). CONCLUSION: Serum PCT levels were significantly lower in patients with acute gouty attack than in patients with bacterial infection. Thus, serum PCT can be used as a useful serologic marker to differentiate between acute gouty arthritis and bacterial infections.

Two-year Follow-up Study of the Relationship between the Changes of Serum Homocysteine and Those of Serum Uric Acid Levels, Lipid Profiles and Renal Function in Gout Patients

OBJECTIVE: Gout is known to be associated with cardiovascular disease (CVD), and hyperhomocysteinemia is one of the risk factors for CVD. We investigated the associations between the change of serum homocysteine (Hcy) level and those of the other parameters including serum uric acid level, renal function, and cholesterol profiles in chronic gout patients with longitudinal follow-up data. METHODS: Ninety-one male patients with chronic gout and 97 age-matched healthy male control subjects were included in the previous study. Among them, 33 patients with gout and 39 healthy control subjects underwent follow-up tests for Hcy levels with an average of 24.00+/-9.12 months in this study. RESULTS: The follow-up data showed that gout patients had significantly higher levels of Hcy in serum than control subjects (16.75+/-5.43 micromol/L vs. 13.17+/-3.83 micromol/L, p=0.002). In gout patients, the change of serum Hcy level after follow up showed positive correlation with the change of creatinine (gamma=0.442, p=0.009) and negative correlation with estimated glomerular filtration rate (eGFR; gamma=-0.528, p<0.001). However, the change of serum Hcy level did not show correlation with the changes of uric acid level or the lipid profiles. CONCLUSION: Serum Hcy level was elevated in gout patients compared with control subjects. The change of serum Hcy level showed negative correlation with the change of eGFR. Hyperhomocysteinemia in gout patients was associated with decreased renal function, but not with serum uric acid or lipid profiles.

Brain meningioma in a patient with systemic lupus erythematosus / 영남의대학술지

Brain meningioma, the most common benign brain tumor, has been reported to account for 13-26% of all intracranial tumors, with a crude incidence rate of 2.3 per 100,000 persons for all types of meningiomas. The prevalence of neuropsychiatric lupus erythematosus is 15-91% and its clinical manifestations are diverse: from mild cognitive dysfunction to serious neurological or psychiatric symptoms. Here, we report the first Korean patient with brain meningioma and systemic lupus erythematosus who had undergone surgical tumor resection.

Seasonality of Gout in Korea: A Multicenter Study

The object of this study was to evaluate the seasonality of gout in Korea. We retrospectively examined data from 330 patients seen at nine rheumatology clinics, treated with urate lowering therapy (ULT) more than one year after stopping prophylactic medication. Demographic data, clinical and laboratory features, and seasonality of gout onset and flares were collected. Season was classified in three-month intervals. The mean age was 52.2 yr and mean disease duration was 26.8 months. The male to female count was 318:12. The onset of acute gouty attacks was obtained in 256 patients. Gout developed most commonly in summer season (36.7%) (P<0.001) and in June (15.6%, P=0.002). During ULT, there were 147 (male 97.3%) gout flares. Although there was no statistically significant difference, gout flares were more common in summer (30.6%). Aggravating factors were identified in 57 flares: alcohol (72.0%) was most common. In the patients who attained target serum uric acid (<6 mg/dL) at the end of prophylaxis, gout flares were high in fall (35.8%) and September (17.0%). In Korea, the summer is most common season of gout onset and there is a tendency for gout flares to increase during ULT in summer/fall season.

New Classification Criteria for Rheumatoid Arthritis / 대한내과학회지

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and the destruction of bone and joints. It also has multiple systemic manifestations, resulting in functional disability and premature mortality. Since the introduction of various disease-modifying anti-rheumatic drugs and new biological agents, early diagnosis and treatment of this disease has become the most important therapeutic strategy. However, the existing classification criteria for RA, the 1987 revised American College of Rheumatology (ACR) classification criteria for RA, have limited diagnostic accuracy for early RA. Therefore, new classification criteria that include early RA are needed. Consequently, a joint working group of the ACR and European League Against Rheumatism (EULAR) was formed to develop a new approach to the classification for RA and developed the 2010 ACR/EULAR classification criteria. This review describes the content and clinical importance of these new classification criteria.

Elevated Serum Homocysteine Levels Were Not Correlated with Serum Uric Acid Levels, but with Decreased Renal Function in Gouty Patients

Hyperhomocysteinemia is one of the important factors of the cardiovascular disease, and gout is well known to be associated with cardiovascular disease. There are a few reports on the serum homocysteine (Hcy) levels in patients with gout, however, the results showed discrepancies. In this study, we measured Hcy levels in patients with gout and examined factors associated with the levels of serum Hcy. Ninety-one male patients with gout and 97 age-matched healthy male controls were enrolled in the study. Serum uric acid levels were not significantly different between gout and healthy control groups. However, serum Hcy levels were significantly higher in patients with gout compared to controls (13.96+/-4.05 microM/L vs 12.67+/-3.52 microM/L, P=0.035). In gout group, patients with 1-2 stages of chronic kidney disease (CKD) had significantly lower serum Hcy than those with 3-5 stages of CKD (13.15+/-3.46 microM/L vs 17.45+/-4.68 microM/L, P<0.001). Multivariate linear analysis revealed an inverse association between serum Hcy and estimated glomerular filtration rate (eGFR) (beta=-0.107, P<0.001). In conclusion, serum Hcy was elevated in male patients with gout. Hyperhomocysteinemia was not correlated with serum uric acid, but it was inversely associated with impaired renal function.