Rheumatoid Arthritis Patients In Korea Research Articles

노인성 류마티스 관절염에서의 당뇨병 위험: 한국인유전체역학조사사업(KoGES) 자료를 이용하여

Rheumatoid arthritis (RA) is one of representative geriatric diseases caused by a combination of various genetic and acquired factors. Chronic progressive systemic inflammation caused by RA is closely associated to the inflammatory pathway underlying the pathogenesis of diabetes mellitus. However, most studies to investigate the association have been conducted mainly in foreign countries, and the study results have been inconsistent. Thus, this study attempted to look at the factors affecting both the pre-diabetes stage and the development of diabetes in RA patients in Korea, and also sought to find risk factors for the development. For this purpose, data from RA patients aged 40 to 69 (n=501) were used among the community-based cohort data from the Korean Genome Epidemiology Study of the Korea Disease Control and Prevention Agency. Simple logistic regression was used to investigate factors influencing the development of pre-diabetes and diabetes. As a result, the prevalence of both pre-diabetes and diabetes in RA patients was found to be higher than that in the general population. RA patients’ risk of developing diabetes was higher if they were female, older, less educated, or had a larger waist circumference, higher body mass index, higher blood pressure, lower triglycerides, and lower high-density lipoprotein cholesterol. However, no association between RA and diabetes was found in factors such as marital status, income, occupation, fatigue, sleep time, smoking, and physical activity. The reason why the association was not found in factors such as the physical activity was discussed in the context of statistical errors made in the process of categorizing the raw data. Despite such weaknesses, the significance of this study was that it was an attempt to pursue the association between RA and diabetes based on demographic, physical measurement, and hematologic data.

Factors associated with selection of targeted therapy in patients with rheumatoid arthritis.

Deciding which drug to choose for targeted therapy is an important step in sequential treatment for rheumatoid arthritis (RA). This study aimed to identify factors for selecting Janus kinase inhibitors (JAKis) rather than biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with RA in real-world practice. We selected RA patients starting JAKis or bDMARDs from single-center prospective cohorts in Korea. Patients were divided into JAKi, tumor necrosis factor (TNF) inhibitor, and non-TNF inhibitor groups. We performed multinomial logistic regression analyses to identify factors associated with selecting JAKis. 145, 205, and 89 patients were included in the JAKi, TNF inhibitor, and non-TNF inhibitor groups. In multinomial regression analysis, the JAKi group was older than the TNF inhibitor group (OR 1.03, 95% confidence interval [CI] 1.01-1.05) but younger than the non-TNF inhibitor group (OR 0.97, CI 0.95-1.00). The JAKi group was less likely to have chronic pulmonary diseases compared with the TNF inhibitor group (OR 0.07, CI 0.01-0.56) or the non-TNF inhibitor group (OR 0.06, CI 0.01-0.50). Higher disease activity assessed by physician (OR 1.80, CI 1.51-2.38) and previous tacrolimus use (OR 2.05, CI 1.20-3.51) were factors suggesting selection of JAKis than TNF inhibitors. Age, pulmonary comorbidities, previous tacrolimus use, and high disease activity assessed by physician were factors influencing the selection of JAKis for RA patients in Korea.

Treatment Sequence After Initiating Biologic Therapy for Patients With Rheumatoid Arthritis in Korea: A Nationwide Retrospective Cohort Study.

To evaluate treatment patterns and healthcare resource utilization (HCRU) after initiating biologic disease-modifying antirheumatic drugs (bDMARDs) in Korean patients with rheumatoid arthritis (RA). Patients newly diagnosed with RA in 2014 were identified and followed up on using the Korean National Health Insurance Database until 2018. The initial line of therapy (LOT) or LOT1 included patients treated with conventional DMARDs (cDMARD). Patients who started a bDMARD were assigned to LOT2 bDMARD. Those who moved from a bDMARD to a Janus kinase inhibitor were assigned to LOT3. Analyzed outcomes were treatment patterns and HCRU in LOT2 bDMARD. The most prescribed initial bDMARD was a tumor necrosis factor inhibitor. Seventy-five percent of patients had changes in treatment after starting a bDMARD, such as addition/removal or switch of a DMARD, and transition to LOT3. For the first and second changes in LOT2 bDMARD, adding a cDMARD to a bDMARD was more common than switching to another bDMARD (7.98% vs. 2.93% for the first change, and 17.10% vs. 6.51% for the second change). Tocilizumab was the most common bDMARD that was switched to. Forty-eight percent of patients had at least one hospitalization after initiating bDMARDs. Of these patients, 64.3% were admitted due to RA-related reasons. This real-world study provides information on treatment characteristics of RA patients in Korea after starting a bDMARD. In contrary to guidelines, cDMARD addition was more often than bDMARD switches in daily clinical practice.

Assessment on Treatments With Conventional Synthetic Disease-modifying Drugs Before Initiating Biologics in Patients With Rheumatoid Arthritis in Korea: A Population-based Study.

To assess pre-biologic treatments with conventional synthetic disease-modifying drugs (csDMARDs) prior to biologics initiation among patients with rheumatoid arthritis (RA). Using Korea National Health Insurance database, we examined pre-biologic treatments of RA patients on the following four items whether 1) initial methotrexate (MTX) therapy was given, 2) MTX dose was escalated up to ≥15 mg/week within 1-year post-diagnosis, 3) prednisone-equivalent glucocorticoid was used at a dose of ≤7.5 mg/day, and 4) glucocorticoid was discontinued within 6 months of treatment. Multivariable logistic regressions identified predictors of items 2) and 4) fulfillment. Among 6,986 biologics initiators with RA, 54.9% used MTX as the 1st csDMARD. Within 1-year post-diagnosis, 85.2% used MTX with half of them achieving a dose of ≥15 mg/week. The majority (75.2%) of patients used glucocorticoids initially and 64.5% were still on glucocorticoids at 6 months, mostly at a dose of ≤7.5 mg/day. csDMARD combination was observed in 85.7%. Item 2) fulfillment was associated with males, younger age, glucocorticoid, combination therapy, cyclo-oxygenase-2 inhibitors, and viral hepatitis. Item 4) fulfillment was associated with males, MTX dose of ≥15 mg/week, combination therapy, viral hepatitis, and hospitalizations. RA patients in Korea were predominantly treated with MTX-based csDMARD combination plus glucocorticoids before initiating biologics, without sufficient MTX dose escalation or glucocorticoid discontinuation. Items 2) and 4) fulfillments were associated with patient age and gender, concomitant treatments, and comorbidities.

The risk of serious infection in rheumatoid arthritis patients receiving tocilizumab compared with tumor necrosis factor inhibitors in Korea

ObjectivesTo examine the risk of serious infections (SIs) among patients with rheumatoid arthritis (RA) treated with tocilizumab compared with tumor necrosis factor inhibitor (TNFi) in Korea. MethodsWe conducted a retrospective cohort study using the Korean National Health Insurance data. The study cohort included patients ≥18 years with RA who were initiated with tocilizumab or TNFi between January 2013 and June 2018. The primary outcome was a composite endpoint of SIs, defined as an infection resulting in intravenous antimicrobial therapy or hospitalization. Secondary outcomes were organ-specific SIs. To control for confounders, we used inverse probability of treatment weighting (IPTW) using propensity score. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a multivariable Cox regression model. ResultsA total of 8794 patients were identified: 1395 and 7399 patients initiated with tocilizumab and TNFi, respectively. The mean follow-up durations were 1.2 years for tocilizumab initiators and 1.0 year for TNFi initiators. After IPTW and adjustment, no increased risk of SIs was observed in tocilizumab versus TNFi (HR, 1.00; 95%CI, 0.90–1.11). In the secondary analysis, tocilizumab was associated with a higher risk of skin and subcutaneous tissue infections (HR, 1.26; 95%CI, 1.02–1.54) and a lower risk of urological and gynecological infections (HR, 0.65; 95%CI, 0.49–0.87) compared to TNFi. ConclusionIn this population-based cohort of RA patients in Korea, tocilizumab was not associated with a higher risk of SI compared to TNFi. However, tocilizumab should be carefully used for patients at high risk for skin-related infections.

Risk factors associated with initiation of a biologic disease modifying anti-rheumatic drug in patients with rheumatoid arthritis: A nested case-control study on 34,925 patients.

To identify risk factors of biological disease-modifying anti-rheumatic drugs (bDMARDs) initiation in patients with rheumatoid arthritis (RA). Using the 2002-2016 Korea National Health Insurance database, we conducted a nested case-control study on seropositive RA patients. Cases (bDMARD users) and controls (users of conventional synthetic DMARDs only) were 1:4 matched on the calendar year/month of RA diagnosis and index dates (bDMARD initiation dates). Potential risk factors from two time periods, 1-year post-RA-diagnosis and 1-year pre-index, were separately assessed on the association with bDMARD initiation by conditional logistic regression analyses. The study included 6985 cases and 27,940 controls. Older age, female gender, use of methotrexate (MTX), leflunomide, or tacrolimus as a first csDMARD, higher initial MTX dose, and initial csDMARD combination during 1-year post-diagnosis were negatively associated with later bDMARD initiation, while use of sulfasalazine as a first csDMARD, corticosteroid therapy, and higher maximal MTX dose were positively associated. Among covariates from 1-year period before bDMARD initiation, use of leflunomide, sulfasalazine, or tacrolimus, parenteral MTX, higher maximal MTX dose, corticosteroid, and csDMARD combination were positively associated with subsequent bDMARD initiation. Effects of comorbidities on bDMARD initiation were heterogenous across involved systems. In this population-based nationwide study, we identified period-specific risk factors of bDMARD initiation among RA patients in Korea. Overall, initial aggressive RA treatment after diagnosis was associated with less use of later bDMARD, while highly intensive therapy observed just before bDMARD initiation rather reflects refractory nature of RA during this period, and did not prevent bDMARD use.

Periodontitis is associated with rheumatoid arthritis: a study with longstanding rheumatoid arthritis patients in Korea.

Background/Aims:A cross-sectional study was undertaken to investigate the association between severity of periodontitis and clinical manifestation of rheumatoid arthritis (RA).Methods:Two hundred sixty-four RA patients and 88 age- and sex-matched controls underwent dental exam. Additionally, clinical manifestations including disease activity and anti-citrullinated protein antibodies were evaluated in RA patients.Results:The prevalence of moderate or severe periodontitis was higher in RA patients compared to controls (63.6% vs 34.1%, p < 0.001). In markers of periodontal inflammation, bleeding on probing was correlated with disease activity score 28 (r = 0.128, p = 0.041), RA disease duration (r = 0.211, p = 0.001), erythrocyte sedimentation rate (ESR; r = 0.141, p = 0.023), anti-cyclic citrullinated peptide antibody (r = 0.183, p = 0.009), and anti-citrullinated α-enolase peptide-1 antibody (r = 0.143, p = 0.025). Gingival index was correlated with RA duration (r = 0.262, p < 0.001), ESR (r = 0.162, p = 0.009), anti-cyclic citrullinated peptide antibody (r = 0.203, p = 0.004) and anti-citrullinated α-enolase peptide-1 antibody (r = 0.225, p < 0.001). Periodontal structural damage represented by probing pocket depth and clinical attachment level were less in RA patients with human leukocyte antigen (HLA)-DRB1 shared epitope compared than those without shared epitope (p = 0.005 and p =0.006, respectively).Conclusions:The prevalence of moderate or severe periodontitis was increased in RA patients compared to controls. Periodontal inflammation was correlated with RA disease duration, ESR, and anti-citrullinated protein antibodies. Periodontal structural damage was less in RA patients with HLA-DRB1 shared epitope.

The psychosocial status of the family members of rheumatoid arthritis patients in Korea.

To investigate the psychosocial aspect of the family members of the patients with rheumatoid arthritis (RA), we conducted a population-based analysis to examine the psychosocial characteristics of family members of RA patients in comparison with the general population. From the Fifth Korea National Health and Nutrition Examination Survey dataset (KNHANES V) (2010-2012), we identified 363 RA patients and selected family members of these patients who were aged 20 years or older (n = 367). The control group was randomly sampled from members of families without RA patients and matched for sex and age (n = 1101). We compared the psychosocial characteristics of family members of RA patients with the control group. Additionally, serial conditional logistic regression models were performed to evaluate the factors that affect psychosocial status of the RA family members, after adjusting for covariates. No significant differences were found in socioeconomic status between the two groups. For psychological factors, stress (85.8 vs 74.7 %, p < 0.001) and depression (7.9 vs 3.3 %, p < 0.001) were more common in the family members of RA patients. The presence of a RA patient in the family showed a positive association with stress [odds ratio (OR) 2.07; 95 % confidence interval (CI) 1.48-2.88, p < 0.001] and depression (OR 2.59, CI 1.55-4.32, p < 0.001), after adjusting for socioeconomic status. Our data show that the family members of RA patients have an increased prevalence of stress and depression. Physicians who treat RA patients should also consider the needs and the burden of family members.

Medical costs for Korean patients with rheumatoid arthritis based on the national claims database

The purposes of this study are to investigate medical resource utilization and medical costs of Korean rheumatoid arthritis (RA) patients and to analyze predictors in relation to medical costs. National claims data on medical treatment were analyzed for the 151,472 RA patients in 2009. For outpatients, the mean annual number of visits was 32.5, and the mean annual total outpatient care costs were 2.0 million KRW (US$1,594) per patient. On the other hand, the mean annual length of stay of inpatients was 22.2 days, and the mean annual total inpatient care costs were 3.8 million KRW (US$3,013). Average annual total medical costs per patient for all of the RA patients were 2.9 million KRW (US$2,310). Total medical costs consisted of 26.1% outpatients' costs, 25.4% inpatient, and 48.6% medication costs, making medication costs a predominant cost driver. In the multiple regression analysis, biologic use was an important cost factor in relation to the annual total medical costs. This study provides information on the cost of illness of RA with the population-based representative RA patients in Korea, which had not been reported until now.

Use of complementary and alternative medicine by rheumatoid arthritis patients in Korea

This study measured the prevalence of use of complementary and alternative medicine (CAM) in Korean patients with rheumatoid arthritis (RA). A trained nurse conducted 20-min questionnaire-based interviews at the hospitals when each patient visited as an outpatient. The questionnaire included questions on demographic information, clinical information, and the use of CAM. Of the 153 respondents, 125 (82%) had used CAM; 37% of those who used CAM had started taking CAM products following suggestions from family members and other relatives. In users of CAM, 35% considered that it improved the symptoms of RA, and 14% felt it was effective in achieving psychological relaxation. We categorized treatment into six CAM categories used by the respondents: 84.0% of patients used traditional Oriental medical treatments, 70.4% used plant- and animal-derived over-the-counter health care products, and 13.6% used manual therapies. Most RA patients (64%) would like to try a new type of CAM. About half of the respondents (48%) expected to receive information about CAM from their general practitioner even if most (72%) did not discuss their use of CAM with their doctor. Most of the RA patients in this study used CAM, and half reported beneficial effects. Despite the presence of adverse side effects, patients tended to use CAM without discussing it with their main physicians, suggesting that physicians should be actively involved in the prescription and use of CAM.

Lack of relationship between vitamin D receptor polymorphism and bone erosion in rheumatoid arthritis.

We performed this study to investigate the possible association between vitamin D receptor (VDR) gene polymorphism and the focal bone erosion in rheumatoid arthritis (RA) patients in Korea. One hundred and fifty-seven RA patients were enrolled and two control groups were selected. The focal bone erosion score was assessed by modified Sharp's method. Genotyping of VDR polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis using two restriction enzyme Taq I and Bsm I. Notably, the distribution of VDR genotype in Korean population was different from Caucasians. The frequencies of "tt" and "BB" genotypes were very rare both in RA patients and in control groups. The frequency distribution of the Taq I and Bsm I genotype was not different between RA patients (TT, 93.6%; Tt, 6.4%; tt, 0%; BB, 0.6%; Bb, 5.1%; bb, 94.3%) and control groups (TT, 90.8%; Tt, 7.5%; tt, 1.7%; BB, 1.4%; Bb, 8.1%; bb, 90.5%). There was no significant difference in the focal bone erosion score (mean +/- SD) according to the VDR genotypes of RA patients (TT, 0.92 +/- 1.79; Tt, 0.4 +/- 0.79; Bb, 0.43 +/- 0.80; bb, 0.92 +/- 1.79; p > 0.05). In conclusion, these results suggest that VDR gene polymorphisms are not associated with the focal bone erosion in RA patients in Korea.

Utilization characteristics of health care service for rheumatoid arthritis patients in Korea.

The purpose of this study was to determine the factors which were responsible for delaying early diagnosis and optimal management of rheumatoid arthritis (RA) in Korea. We interviewed 109 outpatients diagnosed as RA being treated by rheumatologists, and we eventually analyzed 98 patients' data. The median length of time from symptom onset to the first visit to a medical doctor, to diagnosis, and visiting a rheumatologist were 8 weeks, 23 weeks, and 42 months respectively. The subspecialist with whom the patients consulted with for the longest time before visiting a rheumatologist were an orthopaedic surgeon for 51 patients, a Chinese herbal doctor for 19 patients, and a pharmacist for 16 patients. For early diagnosis and optimal management of RA in Korea, we believe that it is necessary to reduce the use of unconventional medical services such as Chinese herbal medicine and nonprescribed medication, and to emphasize rheumatologic and rehabilitative care in the early stage.