Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry.

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

Trends in hospital visits and healthcare costs of gout and seropositive rheumatoid arthritis in Korea from 2010 to 2017 using National Healthcare Claims.

BACKGROUND/AIMS: We examined temporal trends in the rate of gout and seropositive rheumatoid arthritis (RA) hospital visits and healthcare costs in Korea. METHODS: We conducted a serial cross-sectional analysis of Korean national healthcare claims. We calculated the annual increase in hospital visits (emergency department [ED] visits, outpatient visits, and hospitalizations) and total healthcare costs per visit. RESULTS: From 2010 to 2017, the annual rates of ED visits, outpatient visits, and hospitalizations for gout increased from 6.28 to 21, from 638.38 to 1059.55, and from 12.37 to 15.6 per 100,000 persons, respectively. Before 2013, ED visits for gout were most common in patients over 70 years old, but they were most common in those aged between 30 and 49 years after 2013. The number of patients with ED visits, outpatient visits, and hospitalizations for RA from 2010 to 2017 increased from 1.25 to 1.87, from 219.04 to 307.49 and from 8.44 to 12.32 per 100,000 persons, respectively. However, there was no increase in the prevalence of ED visits for RA in any age group except for those older than 70 years. The cost per ED visit for gout significantly decreased from 496.3 to 273.6 US dollar during the study period. There was no significant change in the cost per ED visit for RA between 2010 and 2017. CONCLUSION: There was a large increase in ED visits for gout during the study period. Further studies are needed to analyze the reason behind increased ED visits for gout and suggest ways on how to improve gout care.

Association of body composition with disease activity and disability in rheumatoid arthritis.

BACKGROUND/AIMS: To explore the associations between body composition and pain, disease activity, and disability in rheumatoid arthritis (RA). METHODS: The study enrolled 335 patients with RA and underwent body composition measurement with an InBody analyzer. The associations of body mass index (BMI), body fat mass, and skeletal muscle mass with disease activity score in 28 joints (DAS28), an index derived to measure the subjective component of DAS28 (DAS28-P), a pain visual analogue scale (VAS), and disability measured with the health assessment questionnaire (HAQ) were explored. Obesity was defined as BMI ≥ 25 kg/m2. RESULTS: The median (interquartile range) disease duration was 6 years (3.5 to 9) and the mean DAS28 score was 3.6 ± 1.1. The mean BMI was 23.6 ± 3.6 kg/m2 and 109 patients (32.5%) were obese. Compared with non-obese patients, obese patients had a higher C-reactive protein (1.68 mg/dL vs. < 0.1 mg/dL, p = 0.013), higher pain VAS score (40 vs. 35, p = 0.031), and higher DAS28-erythrocyte sedimentation rate score (3.75 ± 1.18 vs. 3.46 ± 1.11, p = 0.031). In multivariate regression analysis, the DAS28 score in females was positively associated with the current steroid dose, body fat mass, and HAQ score, while the HAQ score in females was associated with older age, DAS28, lower skeletal muscle mass, and higher body fat/skeletal muscle ratio. In the multivariate regression analysis, the DAS28-P score in females was positively associated with body fat/skeletal muscle ratio and HAQ. CONCLUSION: Body composition, such as the body fat mass and body fat/skeletal muscle ratio, is significantly associated with disease activity and disability in female RA patients.

Absence of pain in subjects with advanced radiographic knee osteoarthritis.

BACKGROUND: To investigate the frequency of pain among subjects with advanced radiographic knee osteoarthritis (OA) defined as Kellgren-Lawrence (KL) grade 4 and clinical features associated with pain. METHODS: Subjects from the Hallym Aging Study (HAS), the Korean National Health and Nutrition Examination Survey (KNHANES), and the Osteoarthritis Initiative (OAI) were included. Participants were asked knee-specific questions regarding the presence of knee pain. Clinical characteristics associated with the presence of pain were evaluated with multivariable logistic regression analysis. RESULTS: The study population consisted of 504, 10,152 and 4796 subjects from HAS, KNHANES, and OAI, respectively. KL grade 4 OA was identified in 9.3, 7.6, and 11.5% of subjects, while pain was absent in 23.5, 31.2, and 5.9% of subjects in KL grade 4 knee OA, respectively. After multivariable analysis, female gender showed a significant association with pain in the KNHANES group, while in the OAI group, younger age did. Advanced knee OA patients without pain did not differ from non-OA subjects in most items of SF-12 in both Korean and OAI subjects. Total WOMAC score was not significantly different between non-OA and advanced knee OA subjects without pain in the OAI. CONCLUSIONS: Our study showed that a considerable number of subjects with KL grade 4 OA did not report pain. In patients whose pain arises from causes other than structural damage of the joint, therapeutic decision based on knee X-ray would lead to suboptimal result. In addition, treatment options focusing solely on cartilage engineering, should be viewed with caution.

Development of a Mouse Model of Knee Osteoarthritis Based on Obesity and Bipedal Walking.

To investigate the influence of obesity and obligatory bipedal walking on osteoarthritis (OA) development, 26-week-old C57BL/6 mice were divided into two groups and obesity was induced in one group with a 60% fat diet. After 8 weeks, mice from each group were again divided into two groups and obligatory bipedal exercise was induced with a specially designed treadmill in one group, resulting in four experimental groups (control, control bipedal, obese, and obese bipedal). After 8, 10, and 12 weeks of bipedal walking, knee joints were obtained and graded. Surface fibrillation and matrix proteoglycan depletion, began to appear after 8 weeks of exercise in the bipedal groups and progressed as the duration of the exercise increased. At 12 weeks, cartilage loss extending >75% of articular cartilage was observed in none of the control and obese groups, and in 42.8% and 77.7% of control bipedal and obese bipedal animals, respectively. OA grading was significantly higher in the obese bipedal group compared with the control bipedal group. The von Frey fiber test thresholds decreased significantly in the bipedal groups compared with the control and obese groups. This model can be used to study the pathogenesis of human OA and to evaluate its therapeutic agents. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2411-2419, 2019.

Contribution of subjective Disease Activity Score 28 (DAS28) components to the response to treatment of rheumatoid arthritis.

We investigated the contributions made by the subjective components of the Disease Activity Score 28 (DAS28) to the treatment response of rheumatoid arthritis (RA). In addition, factors associated with poor response to treatment at 6 months, despite normalization of objective measures, were examined. A total of 426 newly diagnosed RA patients were included. The DAS28-P score (the subjective components of the DAS28 relative to the total components) was calculated as DAS28-P = 0.56 ∗ sqrt(TJC28) + 0.014 ∗ (VAS-GH) /0.56 ∗ sqrt(TJC28) + 0.28 ∗ sqrt(SJC28) + 0.7 ∗ In(erythrocyte sedimentation rate (ESR)) + 0.014 ∗ (VAS-GH). The European League Against Rheumatism (EULAR) response was assessed after 6 months of treatment. Of those who failed to attain good EULAR responses, those for whom the objective measures (the ESR, the C-reactive protein level, and swollen joints) were normalized were defined as having failed treatment because of subjective measures. The median (IQR) DAS28 score at baseline was 4.8 (4.04-5.49) and that after 6 months of treatment 3.21 (2.41-3.95). The DAS28-P score fell significantly from baseline to 6 months in good (0.43 versus 0.28, p < 0.001) and moderate responders (0.44 versus 0.4, p = 0.003), but not in non-responders (0.43 versus 0.45, p = 0.727). Younger age, a lower DAS28 score, and a lower DAS28-P score at baseline were related to a good EULAR response. Subjects who failed to respond because of subjective measures tended to have higher DAS28-P scores at baseline. We found that RA patients with high DAS28-P scores, reflecting subjective measures, were less likely to achieve good EULAR responses 6 months after treatment initiation and tended not to be classified as good responders despite normalization of objective measures.

Comparative efficacy of biological agents in methotrexate-refractory rheumatoid arthritis patients: a Bayesian mixed treatment comparison.

BACKGROUND/AIMS: Biological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to 'traditional' disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX). METHODS: Four DMARDs (hydroxychloroquine, sulfasalazine, MTX, lef lunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, inf liximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX-refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC). RESULTS: In total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively. CONCLUSIONS: Based on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients.

Augmented Pain Processing in Primary and Secondary Somatosensory Cortex in Fibromyalgia: A Magnetoencephalography Study Using Intra-Epidermal Electrical Stimulation.

The aim of this study was to investigate augmented pain processing in the cortical somatosensory system in patients with fibromyalgia (FM). Cortical evoked responses were recorded in FM (n = 19) and healthy subjects (n = 21) using magnetoencephalography after noxious intra-epidermal electrical stimulation (IES) of the hand dorsum (pain rating 6 on a numeric rating scale, perceptually-equivalent). In addition, healthy subjects were stimulated using the amplitude corresponding to the average stimulus intensity rated 6 in patients with FM (intensity-equivalent). Quantitative sensory testing was performed on the hand dorsum or thenar muscle (neutral site) and over the trapezius muscle (tender point), using IES (thresholds, ratings, temporal summation of pain, stimulus-response curve) and mechanical stimuli (threshold, ratings). Increased amplitude of cortical responses was found in patients with FM as compared to healthy subjects. These included the contralateral primary (S1) and bilateral secondary somatosensory cortices (S2) in response to intensity-equivalent stimuli and the contralateral S1 and S2 in response to perceptually-equivalent stimuli. The amplitude of the contralateral S2 response in patients with FM was positively correlated with average pain intensity over the last week. Quantitative sensory testing results showed that patients with FM were more sensitive to painful IES as well as to mechanical stimulation, regardless of whether the stimulation site was the hand or the trapezius muscle. Interestingly, the slope of the stimulus-response relationship as well as temporal summation of pain in response to IES was not different between groups. Together, these results suggest that the observed pain augmentation in response to IES in patients with FM could be due to sensitization or disinhibition of the cortical somatosensory system. Since the S2 has been shown to play a role in higher-order functions, further studies are needed to clarify the role of augmented S2 response in clinical characteristics of FM.

Comparison of the disease activity score using the erythrocyte sedimentation rate and C-reactive protein levels in Koreans with rheumatoid arthritis.

OBJECTIVE: The Disease Activity Score based on 28 joints (DAS28) has been widely used in clinical practice and research studies of rheumatoid arthritis (RA). The objective of this study was to evaluate the discordance in the DAS28 based on the erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) levels in Korean patients with RA. METHODS: From August to December 2011, 540 patients with RA who visited two rheumatology clinics affiliated with Hallym University (Korea) and had at least one DAS28 evaluation were examined. RESULTS: The mean age of the included patients was 53 years, and 82% were female. The mean duration of disease was 32.9 ± 41.2 months. The mean DAS28-ESR was higher than the DAS28-CRP (3.65 vs. 3.44; P < 0.001). In the DAS28-ESR group, 126 patients (23.3%) satisfied the criteria for remission versus 134 (24.8%) in the DAS28-CRP group. High disease activity was determined in 80 (14.8%) patients in the DAS28-ESR group and in 43 (8.0%) in the DAS28-CRP group. A comparison of the two groups with respect to four DAS28 disease activity categories showed agreement in 344 patients (63.7%; κ = 0.45). In classifying patients as European League Against Rheumatism (EULAR) responders, agreement between the two methods was shown in 56 patients (71.8%; κ = 0.76). When disagreements between the two scores occurred, more patients had a better EULAR response based on the DAS28-ESR than on the DAS28-CRP (19.2% vs. 8.9%, respectively). CONCLUSION: The discordance between the ESR-based and CRP-based DAS28 could affect clinical treatment decisions for patients with RA.

Effects of hyaluronic acid and γ-globulin concentrations on the frictional response of human osteoarthritic articular cartilage.

Synovial fluid plays an important role in lubricating synovial joints. Its main constituents are hyaluronic acid (HA) and γ-globulin, acting as boundary lubricants for articular cartilage. The aim of the study was to demonstrate the concentration-dependent effect of HA and γ-globulin on the boundary-lubricating ability of human osteoarthritis (OA) cartilage. Normal, early and advance stage articular cartilage samples were obtained from human femoral heads and in presence of either HA or γ-globulin, cartilage frictional coefficient (µ) was measured by atomic force microscopy (AFM). In advanced stage OA, the cartilage superficial layer was observed to be completely removed and the damaged cartilage surface showed a higher µ value (∼ 0.409) than the normal cartilage surface (∼ 0.119) in PBS. Adsorbed HA and γ-globulin molecules significantly improved the frictional behavior of advanced OA cartilage, while they were ineffective for normal and early OA cartilage. In advanced-stage OA, the concentration-dependent frictional response of articular cartilage was observed with γ-globulin, but not with HA. Our result suggested that HA and γ-globulin may play a significant role in improving frictional behavior of advanced OA cartilage. During early-stage OA, though HA and γ-globulin had no effect on improving frictional behavior of cartilage, however, they might contribute to disease modifying effects of synovial fluid as observed in clinical settings.

Altered white matter integrity in the corpus callosum in fibromyalgia patients identified by tract-based spatial statistical analysis.

OBJECTIVE: Although recent imaging studies of fibromyalgia (FM) have converged on a dysfunction of central pain processing as the primary pathophysiologic cause of the disorder, microstructural changes of the white matter (WM) suggestive of abnormalities in the anatomic connectivity of the brain have not been extensively examined. The aim of this study was to investigate WM integrity and its possible relationship to pain symptoms in women with FM. METHODS: Nineteen FM patients and 21 age-, sex-, and education-matched healthy control subjects were included in the study and underwent diffusion-weighted imaging. Group differences in WM integrity, which were assessed via fractional anisotropy (FA), was investigated by applying tract-based spatial statistics. RESULTS: As compared with the healthy control group, the FM group showed a single cluster with lower FA in the left body of the corpus callosum, which was found to be connected to the bilateral sensorimotor cortices (P < 0.05, corrected for multiple comparisons). Furthermore, FA values in the cluster were negatively associated with sensory pain, as measured by the Short-Form McGill Pain Questionnaire, as well as with the relative magnitude of sensory pain versus affective pain (calculated by dividing the sensory score by the affective score). CONCLUSION: Findings of the current study demonstrated that patients with FM had disrupted WM microstructure in the body of the corpus callosum, which was associated with clinical pain intensity. Our results suggest that abnormal interhemispheric transfer might contribute to the heightened pain perception. Our findings further strengthen the hypothesis of centrally augmented pain processing in patients with FM.

A case of bilateral hemarthrosis due to pseudoaneurysms in a patient on anticoagulation therapy.

Hemarthrosis can occur in patients with a predisposition to hemorrhage, such as hemophiliacs or patients on anticoagulation therapy. If hemarthrosis recurs after supportive treatment, however, other etiologies such as anatomical abnormalities should be considered. Spontaneous articular pseudoaneurysm associated with anticoagulation treatment has not been reported previously. We describe a patient on anticoagulation therapy with bilateral hemarthrosis due to pseudoaneurysms. After failing to respond to the correction of over-anticoagulation, magnetic resonance imaging led to the diagnosis of articular pseudoaneurysm. The patient was treated successfully by transarterial embolization.

Prevalence and risk factor of neck pain in elderly Korean community residents.

Neck pain is a common musculoskeletal condition, which causes substantial medical cost. In Korea, prevalence of neck pain in community based population, especially in elderly subjects, has scarcely been reported. We evaluated the prevalence, the severity and the risk factors of neck pain in elderly Korean community residents. Data for neck pain were collected for 1,655 subjects from a rural farming community. The point, 6-months and cumulative lifetime prevalence of neck pain was obtained in addition to the measurement of the severity of neck pain. The mean age of the study subjects was 61 yr and 57% were females. The lifetime prevalence of neck pain was 20.8% with women having a higher prevalence. The prevalence did not increase with age, and the majority of individuals had low-intensity/low-disability pain. Subjects with neck pain had a significantly worse SF-12 score in all domains except for mental health. The prevalence of neck pain was significantly associated with female gender, obesity and smoking. This is the first large-scale Korean study estimating the prevalence of neck pain in elderly population. Although the majority of individuals had low-intensity/low-disability pain, subjects with neck pain had a significantly worse SF-12 score indicating that neck pain has significant health impact.

Characteristics of patients with rheumatoid arthritis in clinical remission: the many aspects of DAS28 remission.

OBJECTIVES: The aim of this study was to observe the clinical characteristics, including the extent of foot and ankle involvement, of Korean patients with rheumatoid arthritis (RA) in remission, defined as Disease Activity Score in 28 joints (DAS28) <2.6. METHODS: Data from a registry of RA patients who visited a rheumatology clinic of a university-affiliated hospital and who were regularly evaluated with DAS28, including the ankle and foot metatarsophalangeal (MTP) joints were enrolled. Patients who were treated with disease-modifying anti-rheumatic drugs for at least three months and who were in DAS28 remission were included in this study. RESULTS: Two hundred and thirteen episodes of DAS28 remission were observed in 147 patients. The mean DAS28 value at the time of remission was 1.84 (range, 0.14-2.59). The mean numbers of swollen joints and tender joints (of the 28 joints examined for DAS28) at the time of remission was 0.4 (range, 0-6) and 1.5 (range, 0-13), respectively. Overall, 11.7% and 38% of the patients in clinical remission had foot MTP/ankle swollen and tender joints, respectively. Additionally, 7% and 8.9%, respectively, of the patients in clinical remission had foot MTP/ankle swollen and tender joints without any involvement of the 28 joints included in the DAS28. CONCLUSIONS: Our results show that RA patients in DAS28 remission frequently have residual disease activity in the ankle and foot joints. Given that fore-foot disease activity can lead to joint damage and disability with respect to weight-bearing activities, these joints should be included in the clinical examination.