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.

SARS-CoV-2 Omicron escapes mRNA vaccine booster-induced antibody neutralisation in patients with autoimmune rheumatic diseases: an observational cohort study.

OBJECTIVES: This study investigates whether COVID-19 vaccines can elicit cross-reactive antibody responses against the Omicron variant in patients with autoimmune rheumatic diseases (ARDs). METHODS: This observational cohort study comprised 149 patients with ARDs and 94 healthcare workers (HCWs). Blood samples were obtained at enrolment, a median of 15 weeks after the second vaccine dose or 8 weeks after the third dose. The functional cross-neutralisation capacity of sera was measured using the Omicron variant receptor-binding domain-ACE2 binding inhibition assay. We assessed the incidence of breakthrough infections and the potential correlation with neutralising responses in participants after receiving third doses. The association of time-from-vaccine and neutralising responses in sera was predicted using linear regression analysis. RESULTS: The mean cross-neutralising responses against the Omicron variant developed after the second dose was 11.5% in patients with ARDs and 18.1% in HCWs (p=0.007). These responses were significantly lower in patients with ARDs than in HCWs after the third dose (26.8% vs 50.3%, p<0.0001). Only 39.2% of the patient sera showed functional neutralisation capacity to the Omicron variant and cross-neutralising responses were shown to be poorly correlated with anti-spike immunoglobulin G titres. Within 6 weeks of immunological assessments, significantly lower Omicron-neutralising responses were detected in sera from patients with ARDs who developed breakthrough infections compared with those who did not (p=0.018). Additionally, a relative decline was implied in neutralising responses against the Omicron variant as a reference to the wild-type virus during 120 days since the third vaccination, with a predicted decay rate of -0.351%/day (95% CI, -0.559 to -0.144, p=0.001). CONCLUSIONS: Striking antibody evasion manifested by the Omicron variant in patients with ARDs and current vaccine-induced immunity may not confer broad protection from Omicron breakthrough infection, highlighting the need for further research on vaccine effectiveness in patients with immune dysfunctions.

Cardiovascular risk associated with allopurinol vs. benzbromarone in patients with gout.

AIMS: With the high prevalence of gout and associated cardiovascular (CV) diseases, information on the comparative CV safety of individual urate-lowering drugs becomes increasingly important. However, few studies examined the CV risk of uricosuric agents. We compared CV risk among patients with gout who initiated allopurinol vs. benzbromarone. METHODS AND RESULTS: Using the Korean National Health Insurance claims data (2002-17), we conducted a cohort study of 124 434 gout patients who initiated either allopurinol (n = 103 695) or benzbromarone (n = 20 739), matched on propensity score at a 5:1 ratio. The primary outcome was a composite CV endpoint of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. To account for competing risk of death, we used cause-specific hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes comparing allopurinol initiators with benzbromarone. Over a mean follow-up of 1.16 years, 2258 patients developed a composite CV event. The incidence rate of the composite CV event was higher in allopurinol initiators (1.81 per 100 person-years) than benzbromarone (1.61 per 100 person-years) with a HR of 1.22 (95% CI 1.05-1.41). The HR for all-cause mortality was 1.66 (95% CI 1.43-1.93) among allopurinol initiators compared with benzbromarone. CONCLUSION: In this large population-based cohort of gout patients, allopurinol was associated with an increased risk of composite CV events and all-cause mortality compared to benzbromarone. Benzbromarone may reduce CV risk and mortality in patients with gout, although more studies are necessary to confirm our findings and to advance our understanding of the underlying mechanisms.

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.

Low levels of serum urate are associated with a higher prevalence of depression in older adults: a nationwide cross-sectional study in Korea.

BACKGROUND: Soluble urate has been shown to serve as an antioxidant, especially in the central nervous system. Although there are intriguing data suggesting that low levels of serum urate are associated with worse outcomes in neurodegenerative diseases, its impact on mental health has not been adequately assessed. Thus, we aimed to investigate the association between serum urate and depression using a large, nationally representative sample. METHODS: Information on participants' socio-demographic characteristics as well as physical and mental health conditions were retrieved from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016 dataset. The Patient Health Questionnaire (PHQ)-9 was applied to identify depressive symptoms. Analyses were stratified by age: young adults (aged 19-39 years), middle-aged adults (aged 40-59 years), and older adults (aged 60 years and older). RESULTS: A total of 5332 participants were included. Serum urate concentrations were divided into sex-specific quartiles based on their distribution: ≤ 4.9 (Q1), 5.0-5.7 (Q2), 5.8-6.6 (Q3), and ≥ 6.7 (Q4) mg/dL in men and ≤ 3.7 (Q1), 3.8-4.3 (Q2), 4.4-4.9 (Q3), and ≥ 5.0 (Q4) mg/dL in women. There was a significant negative linear relationship between serum urate quartiles and PHQ-9 scores in older adults (p for trend = 0.020 in men and p for trend = 0.048 in women). Compared to high levels (Q3 and Q4) of serum urate, low levels (Q1 and Q2) were significantly associated with the overall burden of depression in older women (OR 1.78, 95% CI 1.21, 2.61) and clinically relevant depression in older men (OR 3.35, 95% CI 1.16, 9.70), even after adjustment. CONCLUSIONS: Based on the KNHANES data, low levels of serum urate are associated with a higher prevalence of depression in older adults. This may have clinical implications for mental health.

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.

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.

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

BACKGROUND/AIMS: 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. CONCLUSION: 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 µol/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 µol/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.

The Role of a "Treat-to-Target" Approach in the Long-Term Renal Outcomes of Patients with Gout.

Background: Although gout is accompanied by the substantial burden of kidney disease, there are limited data to assess renal function as a therapeutic target. This study evaluated the importance of implementing a "treat-to-target" approach in relation to renal outcomes. Methods: Patients with gout who underwent continuous urate-lowering therapy (ULT) for at least 12 months were included. The effect of ULT on renal function was investigated by means of a sequential comparison of the estimated glomerular filtration rate (eGFR). Results: Improvement in renal function was only demonstrated in subjects in whom the serum urate target of <6 mg/dL was achieved (76.40 ± 18.81 mL/min/1.73 m2 vs. 80.30 ± 20.41 mL/min/1.73 m2, p < 0.001). A significant difference in the mean change in eGFR with respect to serum urate target achievement was shown in individuals with chronic kidney disease stage 3 (-0.35 ± 3.87 mL/min/1.73 m2 vs. 5.33 ± 11.64 mL/min/1.73 m2, p = 0.019). Multivariable analysis predicted that patients ≥65 years old had a decreased likelihood of improvement (OR 0.31, 95% CI 0.13-0.75, p = 0.009). Conclusions: The "treat-to-target" approach in the long-term management of gout is associated with better renal outcomes, with a greater impact on those with impaired renal function.

The superb microvascular imaging is more sensitive than conventional power Doppler imaging in detection of active synovitis in patients with rheumatoid arthritis.

OBJECTIVES: This study evaluated Superb Microvascular Imaging (SMI) technology for detection of active synovitis in patients with rheumatoid arthritis (RA). METHODS: Between June 2015 and October 2016, 56 patients with RA (42 females; mean age, 53.2 years) underwent gray-scale ultrasound (US) imaging, power Doppler imaging (PDI), and SMI for synovitis of both wrists and hands (total 22 joints), scored for each joint from grades 0 to 3. The sum of grades for 22 joints was determined for gray-scale (SYN-sum), PDI (PDI-sum), and SMI (SMI-sum) according to clinical parameters. Follow-up US was performed in 17 patients (mean interval, 251.6 days). RESULTS: The SMI-sum (7.27 ± 4.56) was significantly higher than the PDI-sum (4.38 ± 3.09, p < 0.001) and the SYN-sum (4.55 ± 3.72, p < 0.001), and was significantly correlated with the erythrocyte sedimentation rate, C-reactive protein (CRP), and Disease Activity Score-28 (DAS28)-CRP (γ = 0.409, p = 0.002; γ = 0.695, p < 0.001; γ = 0.726, p < 0.001, respectively). Moreover, in 28 patients with clinical remission, the SMI-sum (4.32 ± 2.01) was greater than the PDI-sum (2.61 ± 1.60, p < 0.001). In 17 patients with follow-up US, the SMI-sum (2.35 ± 1.73) was significantly greater than the PDI-sum (1.24 ± 1.20; p < 0.001) and was also significantly correlated with DAS28 (γ = 0.880). CONCLUSION: SMI may detect active synovitis with greater sensitivity than PDI in RA patients, even with clinical remission, and is well-correlated with inflammatory parameters during follow-up. KEY POINTS: • SMI correlated well with PDI and was more sensitive for detection of active synovitis in RA. • The SMI-sum was not only of greater value but also more strongly correlated than the PDI-sum with clinical inflammatory indicators including ESR, CRP, and DAS28 on initial and follow-up US examinations. • The SMI-sum was even significantly increased in patients with clinical remission.

Differences in quality of life determinants according to the presence of fibromyalgia in middle-aged female patients with systemic lupus erythematosus: a multicenter, cross-sectional, single-ethnicity cohort.

OBJECTIVE: The purpose of this study was to identify whether determinants of health-related quality of life (HRQoL) in middle-aged female patients with systemic lupus erythematosus (SLE) differed according to the presence or absence of fibromyalgia. METHODS: One hundred and fifty-two patients with SLE and 139 healthy controls (HCs) completed the Medical Outcomes Study 36-Item Short Form (SF-36) and EuroQol EQ-5D questionnaires about HRQoL. Disease activity and cumulative disease damage were assessed with standard indices. Sleep quality was assessed using the Korean version of the Pittsburgh Sleep Quality Index (K-PSQI). RESULT: The mean EQ-5D and physical and mental components of SF-36 were lower in SLE patients with fibromyalgia (n = 41) than in those without fibromyalgia (n = 111) and HCs. The scores in all eight domains of the SF-36 were lower in SLE patients with fibromyalgia than in patients without fibromyalgia and HCs. Poor sleep (defined as a K-PSQI > 5) was reported by 85% of SLE patients with fibromyalgia, by 51% of patients without fibromyalgia, and by 33% of HCs. Multivariate logistic regression analysis showed that lower educational level, cumulative organ damage severity and poor sleep quality were independent determinants of HRQoL in SLE patients with fibromyalgia, whereas disease activity, sleep quality and depressive mood were independent determinants of HRQoL in those without fibromyalgia. CONCLUSION: Poor sleep quality is the common independent risk factor for poor HRQoL in both middle-aged SLE patients with fibromyalgia and without fibromyalgia. Sleep quality improvement may improve HRQoL in female SLE patients, even in those without fibromyalgia.

Development of a Consensus List of Potentially Inappropriate Medications for Korean Older Adults.

BACKGROUND: Korea has recently attained the aged society status and the growth rate of the aging population will be among the most rapid worldwide. The objective of this study was to develop a credible list of potentially inappropriate medications (PIMs) for Korean older adults. METHODS: A new Korean PIMs list was produced through a comprehensive structured expert survey (modified Delphi method). To generate an expert panel, we invited the nomination of experts in geriatric medication from the Korean Geriatric Society, the Korean Academy of Clinical Geriatrics, the Korean Academy of Family Medicine, the Korean Association for Geriatric Psychiatry, and the Korean Association of Geriatric Hospitals. Based on their recommendation, the expert panel consisted of 14 geriatric specialists, including 10 geriatricians (7 family medicine doctors and 3 internal medicine doctors), 3 geriatric psychiatrists, and 1 clinical pharmacist. After 4 rounds, the new Korean PIMs list was finalized. RESULTS: Sixty-two drugs were classified as PIMs for older adults irrespective of comorbidities, including antipsychotics, tricyclic antidepressants, benzodiazepines, non-steroidal anti-inflammatory drugs, and first-generation antihistamines. Forty-eight drugs or drug categories were classified as PIMs for 18 specific conditions that older adults encounter frequently. The expert panel presented the rationale and comments including preferred therapeutic alternatives and exceptional situations for each item. CONCLUSION: We presented a "user-friendly" PIMs list for Korean older adults. Further prospective studies to validate its usefulness in clinical settings and regular updating of the list are required. It is also important to disseminate this list to doctors who prescribe medication to older people.

Monthly Oral Ibandronate Reduces Bone Loss in Korean Women With Rheumatoid Arthritis and Osteopenia Receiving Long-term Glucocorticoids: A 48-week Double-blinded Randomized Placebo-controlled Investigator-initiated Trial.

PURPOSE: Our aim was to investigate the efficacy of monthly oral ibandronate in Korean women with rheumatoid arthritis and reduced bone mineral density (BMD) receiving long-term glucocorticoids. METHODS: Patients (n = 167 women) were randomly assigned (1:1) to receive ibandronate 150 mg or placebo every 4 weeks. Patients had taken glucocorticoid (equivalent of daily prednisolone ≥5 mg) for 3 or more consecutive months before enrollment, and had a lumbar spine 1 to 4 (L1-L4) T-score of < -1.0 and ≥ -2.5. Both groups were provided with daily calcium carbonate and cholecalciferol. The primary end point was the L1 to L4 BMD percent changes at 48 weeks compared with baseline. FINDINGS: Baseline characteristics were comparable between the 2 groups. BMD percent changes in L1 to L4 at 48 weeks were significantly different between the ibandronate versus the placebo group (+3.7% [5.1%] vs -1.9% [4.4%], respectively; P < 0.0001). BMD percent changes at 48 weeks in femur neck and total hip also had similar results (P = 0.0073 and P = 0.0031, respectively). Decrease of serum type 1 collagen C-terminal telopeptide was significant at both 24 and 48 weeks in the ibandronate group. There was no incident of fragility fracture in both groups during the study period. Safety profiles, including adverse events, were comparable between the 2 groups. IMPLICATIONS: Monthly oral ibandronate for 48 weeks is well tolerated and effective in reducing bone mineral loss in women with rheumatoid arthritis on long-term glucocorticoid therapy. Longer follow-up studies are needed to investigate the benefit of ibandronate on fracture rate reduction in this subset of patients. ClinicalTrials.gov identifier: NCT01287533.

Current gout treatment and flare in South Korea: Prophylactic duration associated with fewer gout flares.

AIM: To evaluate treatment patterns and clinical factors affecting gout flare in South Korea. METHODS: We retrospectively examined data from 401 patients seen at nine rheumatology multicenter clinics, under urate lowering therapy (ULT) more than 6 months after stopping prophylactic medication. Demographic data, clinical and laboratory features were collected at the initiation of ULT, upon stopping prophylaxis, and 6 months after. RESULTS: The mean age was 52.2 years and mean disease duration was 25.0 months. The male-to-female count was 387 : 14. The most common ULT starting agent was allopurinol 83.8%. Colchicine (62.3%) was the most commonly prescribed prophylactic agent. During ULT, 134 of the 401 patients (33.4%) experienced at least one gouty attack in the period from stopping prophylaxis to 6 months later. The duration of prophylaxis was different between those with serum uric acid levels below 6 mg/dL and those over 6 mg/dL (P = 0.001). Of the 179 patients (44.6%) who attained target serum uric acid (SUA) levels (6 mg/dL) at the end of prophylaxis, those taking < 6 months of prophylaxis suffered more frequent flares than those taking it ≥ 6 months (42.9% vs. 26.3%, P = 0.041). The time interval to the first attack after stopping prophylaxis was shorter in the < 6 months group than the ≥ 6 months group (13.5 weeks vs. 22.5 weeks, P = 0.007). CONCLUSIONS: Prophylaxis more than 6 months from initiation of ULT, and achieving target SUA (< 6 mg/dL) at the time of stopping prophylaxis is associated with fewer gout flares during ULT.

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.

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.

Comparison of the efficacy and safety profiles of a pelubiprofen versus celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, phase III, non-inferiority clinical trial.

BACKGROUND: Pelubiprofen is a prodrug of 2-arylpropionic acid with relatively selective effects on cyclooxygenase-2 activity. The aim of this study was to compare the efficacy and safety profiles of pelubiprofen with those of celecoxib in patients with rheumatoid arthritis. METHODS: This was a 6-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, non-inferiority clinical trial. The primary end point was non-inferiority of pain decrease from baseline to week-6 as determined using a 100 mm pain visual analog scale (VAS). Pelubiprofen was considered non-inferior to celecoxib if the lower limit of the 97.5% confidence interval for treatment difference [(pain reduction in pelubiprofen group) - (pain reduction in celecoxib group)] was more than -10 mm. The secondary end points were as follows: non-inferiority of (1) reduction of Korean health assessment questionnaire (KHAQ) score; (2) decreased duration of morning stiffness; and (3) decrease in the frequency and total dose of rescue drugs after 6 weeks of treatment. RESULTS: Seventy-seven patients in the pelubiprofen group and 68 patients in the celecoxib group started the study medication. Pelubiprofen was non-inferior to celecoxib with regard to reduction in VAS pain severity (difference, mean ± SD 5.0 ± 20.1; 97.5% CI, -2.3 to ∞). Pelubiprofen was also non-inferior to celecoxib in terms of the secondary end points, such as, decrease in KHAQ score (0.0 ± 0.5, 97.5% CI -0.2 to ∞), decrease in duration of morning stiffness (median 0.0 minute in both groups), and decrease in the frequency (0.7 ± 3.5, 97.5% CI -0.6 to ∞) and total amount (0.7 ± 3.6, 97.5% CI -0.6 to ∞) of rescue medication uses during the 6 week study period. Safety analysis revealed 31.2% patients in the pelubiprofen group and 20.6% patients in the celecoxib group experienced an adverse drug reaction (ADR). The frequency of gastrointestinal ADRs was 20.8 % and 8.8%, respectively. CONCLUSIONS: Pelubiprofen was found to be as effective as celecoxib at pain reduction and for relieving stiffness in RA patients. However, more patients in the pelubiprofen group experienced ADR and the frequency of gastrointestinal ADRs was higher in the pelubiprofen group. ClinialTrials.gov identifier: NCT01781702.

Usefulness of serum leucine-rich alpha-2 glycoprotein as a disease activity biomarker in patients with rheumatoid arthritis.

Our study aimed to investigate whether serum leucine-rich alpha-2-glycoprotein (LRG) levels are elevated in patients with rheumatoid arthritis (RA). In addition, we assessed their correlation with disease activity parameters and pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α). Our study included 69 patients with RA and 48 age- and sex-matched healthy controls. Serum concentrations of TNF-α and LRG were determined by enzyme-linked immunosorbent assay. Serum LRG concentrations were significantly elevated in patients with RA compared with those in healthy controls (30.8 ± 14.4 vs. 22.2 ± 6.1 ng/mL; P<0.001). In patients with RA, serum LRG levels were found to be correlated with disease activity score 28 (DAS28), erythrocyte sedimentation rate, and C-reactive protein levels (γ=0.671; γ=0.612; and γ=0.601, P<0.001, respectively), but not with serum TNF-α levels. Serum LRG levels in patients with an active disease status (DAS28≥2.6) were significantly higher than those in remission (DAS28<2.6) (36.45 ± 14.36 vs. 24.63 ± 8.81 ng/mL; P<0.001). Our findings suggest that serum LRG could contribute to the inflammatory process independent of TNF-α and it may be a novel biomarker for assessing inflammatory activity in patients with RA.

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 µM/L vs 12.67 ± 3.52 µM/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 µM/L vs 17.45 ± 4.68 µM/L, P<0.001). Multivariate linear analysis revealed an inverse association between serum Hcy and estimated glomerular filtration rate (eGFR) (ß=-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.