Folate deficiency is associated with increased radiographic severity of osteoarthritis in knee joints but not in hand joints.

OBJECTIVES: No previous studies have explored the effect of folate deficiency on the severity of osteoarthritis (OA). Therefore, we investigated the relationship between folate level and features on knee and hand radiographs in a large, population-based OA cohort. METHODS: Among 9,260 subjects enrolled in the Dong-gu study, 2,489 who had knee and hand joint radiographs were included. Of these, subjects with a history of amputation or total knee replacement were excluded. Serum folate levels were measured using blood samples collected at the time of enrolment and stored. A semi-quantitative system was used to grade the severity of hand and knee x-ray changes. Linear regression was performed to assess relationships between serum folate levels and knee and hand radiographic scores after adjusting for age, sex, body mass index, smoking, alcohol consumption, education, physical activity, occupation, vitamin D, and ferritin. RESULTS: A total of 2,322 subjects were recruited. After adjusting for confounders, participants with folate deficiency (<4 ng/mL) had higher total (p<0.001), osteophyte (p<0.001), joint space narrowing (p=0.002), tibial attrition (p<0.001), and sclerosis (p=0.005) scores for knee joint radiographs compared to participants with a normal folate level. After adjusting for confounders, the radiographic scores for hand joints did not differ between the groups. CONCLUSIONS: Folate deficiency is associated with increased radiographic severity of OA in knee joints, but not in hand joints. Further studies are needed to explore the differential effects of folate on the severity of knee and hand OA.

Non-adherence to methotrexate was associated with high disease activity and poor health-related outcomes during a 4-year follow-up of rheumatoid arthritis patients.

OBJECTIVES: Although methotrexate (MTX) is the first-line drug for management of rheumatoid arthritis (RA), non-adherence to MTX is highly prevalent and under-recognised. Here, we investigated adherence to MTX and its impact on clinical outcomes during follow-up in patients with RA. METHODS: In total, 367 RA patients were included in this study, with patient visits conducted annually for 4 consecutive years. Adherence was defined by the medication possession ratio during the follow-up period. We divided the patients into two groups; patients who took ≥80% of their prescribed MTX doses and those who did not. In a prospective cohort, the generalised estimating equations were used to identify longitudinal associations between drug adherence and clinical outcomes including disease activity, physical function, and quality of life. RESULTS: Of the 367 RA patients, 8.7% were found to have taken MTX <80% during the period of follow up. After adjustment for confounders, non-adherence to MTX was significantly associated with higher DAS28-ESR during the follow-up period (coefficient ß=0.989, 95%; CI: 0.603-1.375; p<0.001). In addition, non-adherence to MTX was a significant predictor of RAPID3 (coefficient ß=1.847; 95% CI: 0.221-3.472; p=0.026) and EQ-5D (coefficient ß= -0.051; 95% CI: -0.090-0.012; p=0.010) after adjustment for confounding factors. CONCLUSIONS: Non-adherence to MTX was significantly associated with worse clinical outcomes, as evidenced by higher disease activity, poorer physical function, and lower health-related quality of life during a 4-year follow-up of RA patients.

Comparison of three different definitions of low disease activity in patients with systemic lupus erythematosus and their prognostic utilities.

OBJECTIVES: Three definitions of low-level disease activity in patients with SLE have been proposed by different groups. These include minimal disease activity (MDA), low disease activity (LDA) and the lupus low disease activity state (LLDAS). We investigated the performance of these definitions in SLE patients. METHODS: We recruited 299 SLE patients who were followed up annually for 4 consecutive years. We compared the three definitions of low disease activity via longitudinal analysis; we used a generalized, linear-mixed effects model and generalized estimating equations. RESULTS: The LLDAS was significantly associated with a lower SLICC/ACR damage index (ß coefficient=-0.064, 95% CI: -0.129, -0.002, P=0.050), reduced flare (odds ratio = 0.090, 95% CI: 0.034, 0.239, P<0.001), an improved SF-36 physical component score (ß coefficient=0.782, 95% CI: 0.046, 1.519, P=0.037), and an improved SF-36 mental component score (ß coefficient=1.522, 95% CI: 0.496, 2.547, P=0.004). Neither the MDA nor the LDA were associated with these variables. CONCLUSION: The LLDAS definition performs better than the MDA and LDA definitions, showing that LLDAS is associated with less organ damage and flare, and a better quality of life, during follow-up.

Uric acid as a risk factor for progression to chronic kidney disease in patients with lupus nephritis: results from the KORNET registry.

OBJECTIVES: Little is known regarding the effect of hyperuricaemia on the progression of kidney function in patients with lupus nephritis (LN). Thus, we investigated the effect of uric acid (UA) on the long-term outcome of patients with biopsy-proven LN. METHODS: Data were obtained from KORNET, a prospective longitudinal systemic lupus erythematosus registry in the Republic of Korea. All 137 patients with LN included in this study had undergone a kidney biopsy and were subsequently treated with immunosuppressants. The patients were divided into two groups: UA ≤7 mg/dL and >7 mg/dL; their sociodemographic, clinical, treatment-related data, and outcomes were compared. Cox-proportional regression analyses were performed to identify independent predictors of renal outcome in patients with LN. RESULTS: Among the 137 patients, 37 (27.0%) had UA >7 mg/dL. This higher UA group included fewer women, but more patients with hypertension, proliferative type LN, and a chronicity index >12. The 24-h urinary protein excretion and the creatinine level were higher in this group; haemoglobin, platelet, and albumin levels were lower. During 85.0 months of follow-up, complete remission at 1 year was less frequent in the higher UA group, whereas chronic kidney disease (CKD) and end-stage renal disease were more prevalent. In the Cox proportional hazards regression analysis, UA >7 mg/dL was a signi cant predictor of progression to CKD in patients with LN (hazard ratio=2.437; p=0.020). CONCLUSIONS: Our findings suggest that hyperuricaemia at LN onset is an independent risk factor that predicts the development of CKD in patients with LN.

HAQ score is an independent predictor of sustained remission in patients with rheumatoid arthritis.

We assessed potential predictors of sustained remission for 2 years according to the Disease Activity Score in 28 joints (DAS28)-CRP in patients with rheumatoid arthritis (RA). We obtained data for 290 RA outpatients, from July 2009 to September 2012. Sociodemographic data and answers to questionnaires were collected in face-to-face interviews. Remission was defined according to DAS28-CRP. Sustained remission was defined as meeting criteria for remission in the annual assessment for two consecutive years. Predictive factors of sustained remission according to DAS28-CRP were assessed by univariate and multivariate analyses. Of the 290 RA patients, the baseline remission level, according to DAS28-CRP, was 54.5%. During 2 years of follow-up, the sustained remission rate was 24.5%. RA patients who achieved sustained remission, according to DAS28-CRP, were younger, and had a shorter duration of symptoms, longer period of education, higher monthly income, lower Health Assessment Questionnaire (HAQ) score, lower physician global assessment, lower patient global assessment, lower patient pain assessment, and higher EQ-5D at baseline. Multivariate analyses showed that the baseline HAQ score was independently associated with sustained remission for 2 years according to DAS28-CRP (OR 0.298, 95% CI 0.115-0.770; p = 0.012). A lower HAQ score at baseline was an independent predictor of sustained remission at 2 years, according to DAS28-CRP. Thus, HAQ scores could be useful when stratifying patients according to risk for flare-ups in the clinic.

Increased alcohol intake is associated with radiographic severity of knee and hand osteoarthritis in men.

Observational studies have shown controversial associations between alcohol intake and radiographic osteoarthritis (OA). This study investigated whether this association was causal using a Mendelian randomization (MR) study in a population-based cohort in Korean. The study enrolled 2429 subjects (1058 men, 1371 women) from the Dong-gu Study. X-rays of the hand and knee joints were scored using a semi-quantitative grading system to calculate the total score of the hand and knee joints. ALDH2 rs671 genotyping was performed by high-resolution melting analysis. MR instrumental variable analysis and observational multivariable regression analysis were used to estimate the association between genetically predicted alcohol intake and the radiographic severity of OA. Subjects with the G/G genotype had a higher current alcohol intake than those with the G/A and A/A genotypes in both men and women (all P < 0.001). Men with the G/G genotype had higher total knee (P < 0.001) and hand scores (P = 0.042) compared to those with the G/A and A/A genotypes after adjusting for age and body mass index, but not in women. In the observational multivariable regression analysis, each alcohol drink per day in men was associated with increased knee (P = 0.001) and hand joint scores (P = 0.013) after adjustment, but not in women. In our MR analysis, utilizing ALDH2 rs671 genotypes as instrumental variables for alcohol consumption, has shown a significant link between each additional daily alcohol drink and increased radiographic joint severity in men.

Risk factors for thrombotic events in Korean patients with systemic lupus erythematosus.

Thrombotic events (TE), including deep vein thrombosis, stroke, and myocardial infarction, occur in 30-40% of patients with systemic lupus erythematosus (SLE) resulting in substantial morbidity and mortality. We explored the risk factors for TE in SLE patients. We analyzed data obtained during a prospective cohort based on the KORean lupus NETwork (KORNET) registry, and enrolled 259 SLE patients with clinical data available at the onset of SLE. TE was defined as the presence of arterial or venous thrombosis. Multivariate Cox-proportional hazards analysis was performed to investigate risk factors for TE. During a mean follow-up of 103.3 months (SD 53.4), 27 patients (10.4%) had a TE. In multivariate analysis, hypertension (hazard ratio [HR] 7.805, 95% confidence interval [CI]: 1.929-31.581; P = 0.004), anti-phospholipid syndrome (APS) (HR 12.600, 95% CI: 4.305-36.292; P < 0.001), mean daily prednisolone > 5 mg/day (HR 3.666, 95% CI: 1.318-10.197; P = 0.013), and SLICC/ACR Damage Index (SDI) score (HR 1.992, 95% CI: 1.465-2.709; P < 0.001) were significantly associated with the development of TE in SLE patients. Instead, use of an ACEi or ARB (HR 0.159, 95% CI: 0.043-0.594; P = 0.006) was a protective factor against TE development in these patients. In conclusion, hypertension, higher mean daily dose of prednisolone, diagnosis of APS, and higher SDI were risk factors for TE in patients with SLE. On the other hand, the use of an ACEi or ARB was associated with a reduced risk of TE.

Comparison of the AAPT Fibromyalgia Diagnostic Criteria and Modified FAS Criteria with Existing ACR Criteria for Fibromyalgia in Korean Patients.

INTRODUCTION: Recently, new sets of diagnostic criteria were proposed, including criteria by the ACTTION-American Pain Society Pain Taxonomy (AAPT) group and Fibromyalgia Assessment Status (FAS) 2019 modified criteria for fibromyalgia (FM). Here, we explored the performances of the AAPT criteria and modified FAS criteria for diagnosing FM compared to existing American College of Rheumatology (ACR) criteria. METHODS: We enrolled 95 patients with FM and 108 patients who had other rheumatologic disorders, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and myofascial pain syndrome. All patients were classified using proposed criteria including the 1990, 2010, 2011, and 2016 versions of the ACR criteria. RESULTS: In patients with existing FM diagnoses, FM was diagnosed in 56.8% using the AAPT criteria and in 60.0% using the modified FAS criteria. However, FM was diagnosed in 37.9%, 97.9%, 90.5%, and 94.7% of those patients using the 1990, 2010, 2011, and 2016 ACR criteria, respectively. For the AAPT criteria, the sensitivity was 56.8% and the specificity was 94.4%. For the modified FAS criteria, the sensitivity was 60.0% and the specificity was 92.6%. The areas under the receiver-operating characteristic curve were 0.852 (95% confidence interval [CI] 0.801-0.903) for the AAPT criteria and 0.903 (95% CI 0.861-0.944) for the modified FAS criteria, which were lower than the existing ACR criteria. CONCLUSIONS: Although the AAPT criteria and modified FAS criteria have simplified the diagnostic criteria to facilitate patient identification, their poor diagnostic accuracy will limit the adoption and spread of these criteria in routine clinical practice.

Elevated resting heart rate is associated with increased radiographic severity of knee but not hand joints.

Although the resting heart rate (RHR) predicts the clinical outcomes of cardiovascular disease, chronic obstructive lung disease, diabetes mellitus, and the risk of cancer, its role in patients with musculoskeletal diseases, such as osteoarthritis (OA), remains unclear. We explored the association of the RHR with the extents of radiographic changes in the knees and hands of 2369 subjects from the Dong-gu Study. The radiographic hand and knee joint findings were graded semi-quantitatively; we calculated total hand and knee joint scores. Multiple linear regression was performed to examine the associations between the RHR and the radiographic characteristics of these joints. For the knee joints, the RHR was associated positively with the total (p < 0.01), osteophyte (p < 0.01), joint space narrowing (JSN; p < 0.01), and tibial attrition (p = 0.02) scores after adjustment for age, sex, body mass index, smoking status, alcohol consumption, educational and physical activity levels, and comorbidities. For the hand joints, the RHR was associated positively with the JSN (p = 0.01) and subchondral cyst (p < 0.01) scores after such adjustment. The RHR was not associated with the total, osteophyte, sclerosis, erosion, or malalignment score for the hand joints. This study is the first to reveal an association between the RHR and the radiographic severity of knee, but not hand, OA.

Increased adiponectin levels are associated with higher radiographic scores in the knee joint, but not in the hand joint.

Several studies have evaluated the association between serum adiponectin levels and knee and hand osteoarthritis (OA); mixed results have been reported. We investigated the relationship between OA and serum adiponectin levels according to the radiographic features of knee and hand OA. A total of 2402 subjects was recruited from the Dong-gu Study. Baseline characteristics were collected via a questionnaire, and X-rays of knee and hand joints were scored using a semi-quantitative grading system. The relationship between serum adiponectin levels and radiographic severity was evaluated by linear and logistic regression analysis. Subjects in the higher serum adiponectin levels tertiles were older and had a lower body mass index (BMI) than those in the lower tertiles. Regarding knee joint scores, serum adiponectin levels was positively associated with the total (P < 0.001), osteophyte (P = 0.003), and joint space narrowing (JSN) scores (P < 0.001) after adjustment for age, sex, BMI, smoking, alcohol consumption, education, and physical activity. In terms of hand joint scores, no association was found between serum adiponectin levels and the total, osteophyte, JSN, subchondral cyst, sclerosis, erosion, or malalignment score after the above-mentioned adjustments. Similarly, subjects with serum adiponectin levels above the median had higher total radiographic scores in the knee joints, but not in the hand joints, after adjustment. An increased serum adiponectin levels was associated with a higher radiographic score in the knee joint, but not in the hand joint, suggesting the involvement of different pathophysiologic mechanisms in the development of OA between those joints.

Effects of add-on transcranial direct current stimulation on pain in Korean patients with fibromyalgia.

Despite promising preliminary results of transcranial direct current stimulation (tDCS) treatment in patients with fibromyalgia (FM), several issues need to be addressed, including its limited efficacy, low response rate, and poor tolerability. We investigated the efficacy and safety of tDCS as an add-on treatment for chronic pain in Korean patients with FM. This study enrolled 46 patients who were refractory to pain medications from May 2016 to February 2017. A conventional tDCS device was used to supply 2 mA of current for 20 min on five consecutive days. The primary end-point was a change in visual analogue scale (VAS) pain score at the end of treatment; secondary end-points included changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and Medical Outcomes Study Sleep Scale (MOS-SS) scores. After tDCS, 46 patients showed clinical improvements in VAS pain scores on days 6, 13, and 36 compared with day 0 (p < 0.001). Improvement in FIQ was seen on day 13. The BDI decreased significantly on days 6 and 36, and BFI improved significantly on days 6 and 13. There were no significant improvements in STAI-I, STAI-II, and MOS-SS scores after tDCS. No serious adverse events were observed. Our results suggest that tDCS can result in significant pain relief in FM patients and may be an effective add-on treatment.

Basal metabolic rate and Charlson Comorbidity Index are independent predictors of metabolic syndrome in patients with rheumatoid arthritis.

OBJECTIVE: To prospectively analyze predictors of metabolic syndrome (MetS) in patients with rheumatoid arthritis (RA) during 2years of follow-up. METHODS: We recruited 319 consecutive patients with RA who did not have MetS. MetS was defined in accordance with the modified National Cholesterol Education Program/Adult Treatment Panel III 2005 for Asian populations. Sociodemographic data, laboratory findings, disease activity data, and medication history were collected during face-to-face interviews at baseline and follow-up. Independent predictors of MetS were assessed by univariate and multivariate logistic regression analyses. RESULTS: Of the 247 patients with RA who completed the 2-year follow-up, 37 (15.0%) developed MetS. At baseline, these patients were older and had higher body mass index, waist circumference, waist-hip ratio, skeletal muscle mass, body fat mass, percent body fat, and Charlson Comorbidity Index scores, as well as lower basal metabolic rate (BMR). Moreover, these patients with MetS took less hydroxychloroquine and more oral hypoglycemic agents; they also had lower European Quality of Life Health-state Questionnaire scores. After exclusion of variables associated with MetS composition, multivariate analysis identified BMR (odds ratio [OR]=0.205, 95% confidence interval [CI]: 0.078-0.541, P=0.001) and Charlson Comorbidity Index score (OR=2.191, 95% CI: 1.280-3.751, P=0.004) as significant predictors of MetS. CONCLUSIONS: Our study showed that the annual incidence rate of MetS was 11.5% in patients with RA. Moreover, the development of MetS was associated with BMR and Charlson Comorbidity Index score at baseline.

Performance of the revised 2016 fibromyalgia diagnostic criteria in Korean patients with fibromyalgia.

AIM: Recently, the revised 2016 version of the 2010/2011 fibromyalgia (FM) criteria was released. No study has yet assessed whether the 2016 criteria perform better than the previous criteria. Therefore, we validated a Korean version of the revised FM criteria and explored whether they were better than the previous criteria in terms of diagnostic accuracy. METHODS: We enrolled 86 FM patients and 89 patients with various rheumatological disorders, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and myofascial pain syndrome. All patients were invited to complete a questionnaire that included the revised Fibromyalgia Impact Questionnaire (FIQ), the EuroQol five-dimensional questionnaire (EQ-5D), and the Multidimensional Health Assessment Questionnaire (MD-HAQ). RESULTS: The test-retest reliability of the revised criteria was assessed in 30 patients after 2 weeks; the Spearman coefficient ranged from 0.616 to 0.910 and the Cronbach's alpha was 0.942 (95% CI: 0.930-0.964). The revised criteria correlated significantly with the revised FIQ score (P < .001), the EQ-5D score (P < .001), and the MD-HAQ score (P < .001). Using the revised criteria, FM was diagnosed in 94.2% of patients with a prior diagnosis of FM, and in 10.1% of those with other rheumatological disorders. The sensitivity and specificity of the revised criteria were 93.1% and 90.7%, respectively. The area under the receiver operating characteristic curve of the revised criteria was 0.966, higher than those of the 1990, 2010, and 2011 criteria. CONCLUSION: The revised criteria are reliable and valid when used to diagnose patients with FM, and are better than the previous criteria.

Chronicity index, especially glomerular sclerosis, is the most powerful predictor of renal response following immunosuppressive treatment in patients with lupus nephritis.

AIM: Renal responses to immunosuppressive agents in patients with lupus nephritis (LN) differ depending on ethnicity, follow-up duration, disease severity and treatment. Thus, we evaluated predictors of complete remission during the first year following immunosuppressive treatment in patients with LN. METHODS: We retrospectively reviewed 79 patients who underwent kidney biopsy prior to the start of induction treatment and who were subsequently treated with immunosuppressive drugs for at least 6 months and followed-up for more than a year. Complete remission (CR) was defined as inactive urinary sediment, a decrease in urinary protein to a creatinine ratio < 0.2, and normal or stable renal function. Multivariate analyses were performed using the logistic regression model to identify independent predictors of CR in LN patients. RESULTS: After 1 year, renal response was achieved in 39 of 79 patients (49.4%) treated with immunosuppressive drugs. Intravenous cyclophosphamide was most commonly used as a treatment, followed in descending order of frequency by mycophenolate mofetil, azathioprine and cyclosporine. CR was associated with disease duration at the onset of LN, serum erythrocyte sedimentation rate, chronicity index on renal histology, glomerular sclerosis, tubular atrophy, interstitial fibrosis, and the use of hydroxychloroquine at the onset of LN. In multivariable regression analysis, glomerular sclerosis in the chronicity index was a significant predictor of complete remission in LN patients. CONCLUSION: Our findings suggest that glomerular sclerosis in the chronicity index is an independent predictor of CR after the start of therapy in LN patients.