Potential clinical utility of a novel optical tomographic imaging for the quantitative assessment of hand rheumatoid arthritis.

Optical tomographic imaging (OTI) was reported to be a novel technique for the early diagnosis and disease activity assessment of rheumatoid arthritis (RA). This study aimed to evaluate the clinical utility of OTI for the detection of hand synovitis of RA patients. Manu-scan was used to perform imaging targeting the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints in 12 RA patients and three controls. The enrolled RA patients also underwent magnetic resonance imaging (MRI) and bone scintigraphy (BS) to provide reference images. Of the 181 joints feasible for OTI analysis, 140 joints (111 in RA patients and 29 in controls, 77.3%) in which the difference of the OTI indices in the two measurements was within 20% were evaluated. The OTI indices in RA joints were significantly lower than those in control joints (p < 0.001). Overall, the OTI indices in RA joints decreased as the synovitis grades on MRI or BS increased. Moreover, OTI was able to discriminate between RA and control joints (AUC = 0.815, 95% CI 0.739-0.891), even if RA joints were normal on physical examination (AUC = 0.714, 95% CI 0.594-0.834). OTI was in good agreement (kappa = 0.60) with MRI for evaluating synovitis in RA patients and showed positive results in 11.4% of clinically asymptomatic joints. OTI in this study showed the potential to be a supplementary imaging modality for the quantification of synovial inflammation in PIP and MCP joints of RA patients. Further large-scale trials are needed to confirm these findings.

Mortality, disability, and healthcare expenditure of patients with seropositive rheumatoid arthritis in Korea: A nationwide population-based study.

BACKGROUND: We investigated the mortality and disability rate, as well as the healthcare expenditure, for patients with newly diagnosed seropositive rheumatoid arthritis (RA) who were followed-up for up to 10 years, compared to the general population in Korea. METHODS: We conducted a nationwide population-based study using a National Health Insurance Service-National Sample Cohort of the Korean population, consisting of 1 million individuals who submitted medical care claims between 2002 and 2013. RA was identified using as the International Classification of Diseases code M05 (seropositive RA), with prescription of any disease-modifying anti-rheumatic drug (DMARD). Our analysis was based on the data of 1655 patients with incident seropositive RA and 8275 non-RA controls. The controls were matched to the RA cohort by sex, age at the time of diagnosis, duration of follow-up, geographic region, type of social security, and household income. RESULTS: The most commonly used conventional synthetic DMARDs were hydroxychloroquine (71.30%) and methotrexate (69.5%), with adalimumab being the most commonly used biologic DMARD (2.54%). The mortality rate was significantly higher in the RA than the control group (incidence rate ratio [IRR] 1.29, 95% confidence interval [CI] 1.02-1.64) in the first 10 years after diagnosis. Specifically, mortality due to infectious diseases (IRR 4.41, 95% CI 1.60-12.17) and pneumonia (IRR 3.92, 95% CI 1.46-10.53) was significantly higher in the RA than control group. The disability rate was higher in the RA than control group over the first 10 years of the disease (IRR 2.27, 95% CI 1.77-2.92), which was attributed to a higher incidence of physical disability (IRR 3.81, 95% CI 2.81-5.15). Annual health expenditure was greater for the RA than the control group. CONCLUSIONS: Therefore, the rate of mortality and disability, as well as healthcare expenditure, are higher for patients with RA over the first 10 years of the disease onset, than the general population of Korea. The use of claim data has limited the quality of information and there is a limit to the observation period, and we expect the prospective national-wide multicenter cohort for longer period to overcome these limitations.

Comorbidity, disability, and healthcare expenditure of ankylosing spondylitis in Korea: A population-based study.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease typically diagnosed in young age and follows a chronic progressive course. Its impact on the patient is life-long and the burden that AS exerts on society is increasing cumulatively every year. We aimed to quantify the burden of AS and to identify the factors associated with comorbidity, disability, and healthcare expenditure in Korean AS patients. METHODS: We conducted a nationwide, population-based study using health insurance data (2003-2013). The analysis included individuals with incident AS (1,111 patients) and controls (5,555 patients) matched by age, sex, income, and geographic region. The incidence rates of extra-articular manifestations (EAMs), comorbidities, mortality, and disability (type and severity) were compared between AS patients and controls. Annual health expenditure per patient was also analyzed. Associations were expressed as odds ratios (ORs) with 95% confidence intervals (95%CIs). RESULTS: During the follow-up, 28% of AS patients experienced at least one EAM. AS diagnosis was significantly associated with Charlson comorbidity index ≥3 (OR 2.18, 95% CI 1.91-2.48). Disability rate was higher in AS patients than in controls regardless of cause and severity (OR 2.94, 95% CI 2.48-3.48), but crude incidence rate ratios for mortality were not significantly higher. On multivariate analysis, male sex (OR 3.18, 95% CI 2.13-4.75), presence of an EAM (OR 1.63, 95% CI 1.15-2.32), and older age at diagnosis (OR 1.27, 95% CI 1.20-1.35) were evidently associated with increased disability in AS. Presence of an EAM was also associated with increased AS-unrelated expenditures in biologic-naïve patients (median, 1112 vs. 877 USD per person, P < 0.05). CONCLUSIONS: In patients with AS, demographic factors and systemic manifestations including EAMs and other comorbidities were associated with increased disability and healthcare expenditures.

2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p<0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

OBJECTIVE: To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). METHODS: Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. RESULTS: Consensus was reached for a conjoint analysis-based continuous model using absolute percent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (P < 0.001). CONCLUSION: The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute percent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.

Rheumatoid arthritis patients fulfilling Korean National Health Insurance reimbursement guidelines for anti-tumor necrosis factor-α treatment and comparison to other guidelines.

The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheumatoid arthritis (RA) patients with the Korean National Health Insurance (KNHI) reimbursement eligibility criteria and with American College of Rheumatology (ACR) recommendations, Japan College of Rheumatology (JCR) guidelines and British Society for Rheumatology (BSR) guidelines. Between December 2011 and August 2012, outpatients from 17 South Korean general hospitals diagnosed with RA according to the 1987 ACR criteria were enrolled into a noninterventional, cross-sectional, observational study. Of 1700 patients (1414 female (83.2 %), mean age of 56.6 ± 12.0, mean disease duration 97.9 ± 91.8 months), 306 (18.0 %) had used anti-TNFα agents, and 224 (13.2 %) were currently using an anti-TNFα agent. Of 1394 anti-TNFα-naive patients, 32 (2.3 %) met KNHI reimbursement guidelines, 148 (10.6 %) met ACR recommendations, and 127 (9.1 %) and 126 (9.0 %) were considered eligible for anti-TNFα agents according to JCR and BSR guidelines, respectively. The main discrepancy was the higher active joint count required by the KNHI eligibility criteria. In the opinion of treating rheumatologists, the KNHI reimbursement criteria ineligibility accounted for 15.3 % (n = 213) of the reasons for not initiating anti-TNFα agents in anti-TNFα-naive group. The anti-TNFα user group showed significantly higher disease activity than the anti-TNFα-naive group based on DAS28 score. In comparison with the ACR recommendations and JCR and BSR guidelines, fewer patients met KNHI reimbursement eligibility criteria for anti-TNFα agents. The current amendment of the KNHI criteria based on DAS28 score will improve an access to biologic agents including anti-TNFα treatment for South Korean patients with active RA.

A decision model for the watch-and-wait strategy in systemic sclerosis-associated interstitial lung disease.

OBJECTIVE: To develop a decision model to identify SSc-associated interstitial lung disease (ILD) patients who are eligible for watchful waiting at ILD diagnosis. METHODS: One hundred and fifty-one SSc-ILD patients who received medical care at Seoul National University Hospital from 1986 to 2013 were enrolled in this retrospective cohort study. ILD was diagnosed by chest CT. Patients with and without immunosuppressive treatment were compared in terms of characteristics at ILD diagnosis to identify distinguishing variables. After multivariate analysis, a decision model for watchful waiting was formulated. Its validity was assessed by comparing the survival of patients whose management in real practice did and did not accord with the management recommended by the model. RESULTS: The untreated group had better survival than the immunosuppressive treatment group (P = 0.0316, by log-rank test). The untreated group was less likely to have gastrointestinal involvement (P = 0.008) and pulmonary arterial hypertension (PAH), as determined by echocardiography) (P = 0.015) and more likely to have favourable initial forced vital capacity (P = 0.0004), favourable initial lung diffusion capacity for carbon monoxide (P = 0.0002) and a low CT grade (P < 0.001). The final watchful waiting decision model included lack of PAH and limited ILD extent on CT. Application of the model to the cohort revealed that patients who were eligible for watchful waiting (as determined by the model) and underwent this management strategy had better survival than eligible patients who underwent immunosuppressive treatment (P = 0.048, by log-rank test). CONCLUSION: Watchful waiting may be effective for SSc-ILD patients who have minimal pulmonary involvement on CT and lack PAH on echocardiography at baseline.

Cost-of-illness and quality of life in patients with ankylosing spondylitis at a tertiary hospital in Korea.

The objectives of this study were to estimate the cost-of-illness (COI) and health-related quality of life (HRQOL) in patients with ankylosing spondylitis (AS) in Korea and to evaluate the effects of socio-demographic and clinical factors on the COI and the HRQOL. Face-to-face interview surveys were taken from patients with AS at the Rheumatology Clinic of Seoul National University Hospital. Direct medical and non-medical costs, indirect costs (productivity loss due to job loss and sick leave), and deterioration of HRQOL in patients with AS were measured. Factors associated with COI and HRQOL were analyzed with multiple regression and multivariate logistic regression. A total of 191 patients with AS was enrolled in the study. The COI in patients with AS amounted to 11,646,180 Korean Won (KRW) per patient, and their HRQOL was 0.62. As functional severity worsened, the total costs increased (class I, KRW 7.7 million; class II, KRW 12.9 million; classes III & IV, KRW 25.2 million) and the HRQOL scores decreased (class I, 0.72; class II, 0.61; classes III & IV, 0.24). Functional severity is the major determinant of the COI and HRQOL in patients with AS.

Treating rheumatoid arthritis to target: recommendations assessment questionnaire in Korea.

Treat rheumatoid arthritis (RA) to target (T2T) is an international initiative to provide the rheumatology community with clear direction on treatment targets for RA. We performed a nationwide survey in Korea among rheumatologists to measure the levels of agreement with international T2T recommendations and to assess their practical application in Korea. A questionnaire was administered to 111 physicians. Responses were assessed using a 10-point Likert scale for the level of agreement with each of 10 recommendations and a 4-point Likert scale for the degree to which each recommendation was being applied in current daily practice. Respondents were also asked whether these recommendations would result in a change in their practice. This report outlines the consensus reached for T2T in Korea and compares those results with data obtained internationally. Agreement with T2T recommendations was high with average response scores above 8.3. The majority of respondents indicated they applied the recommendations "always" and "very often" in daily practice. More than half of the participants not currently applying these recommendations were willing to change their practice, but the percentage of Korean physicians willing to change was consistently more than the international average. The results of this survey of T2T recommendations in Korean rheumatologists revealed a good correlation with the views of the international rheumatology community. These results could be utilized to define key issues for better disease control in daily practice and used as a reference to improve the treatment environment.

The EULAR Sjogren's syndrome patient reported index as an independent determinant of health-related quality of life in primary Sjogren's syndrome patients: in comparison with non-Sjogren's sicca patients.

OBJECTIVE: To investigate the significant determinants of health-related quality of life (HRQOL) and the association of the EULAR Sjögren's syndrome patient reported index (ESSPRI) with clinical parameters including HRQOL in Korean patients with primary Sjögren's syndrome (pSS) compared with non-SS sicca patients. METHODS: We prospectively analysed 104 pSS and 42 non-SS sicca patients. Clinical data including Short Form 36 (SF-36) scores, self-assessments for symptoms and ESSPRI were cross-sectionally collected. RESULTS: Although most self-assessments and HRQOL statuses were comparable, different association patterns between HRQOL and symptoms were observed in pSS and non-SS sicca patients. pSS patients with low HRQOL had significantly higher ESSPRI scores [P = 7.6 × 10(-6) for physical component summary (PCS) subgroups and P = 0.0015 for mental component summary (MCS) subgroups] and ESSPRI scores showed a significant association with all SF-36 scales in pSS patients (all P ≤ 0.0020). Moreover, in multivariate linear regression analyses, ESSPRI (P = 0.035) and depression (P = 4.1 × 10(-14)) were significantly correlated with the PCS and the MCS, respectively. However, in the non-SS sicca group, xerostomia inventory (XI) scores were higher in the low PCS subgroup (P = 0.031) and this correlated with five SF-36 scales (all P ≤ 0.046). XI scores (P = 0.0039) and anxiety (P = 7.9 × 10(-10)) were the main determinants of the PCS and MCS, respectively. CONCLUSION: HRQOL levels were differentially associated with clinical facets in pSS and non-SS sicca patients, although the groups had similar clinical symptoms and HRQOL reduction. Because depression and ESSPRI are major determinants of HRQOL in Korean pSS patients, ESSPRI is suggested to be disease-specific for pSS.

Cost of illness and quality of life of patients with rheumatoid arthritis in South Korea.

OBJECTIVE: To estimate the cost of illness (COI) and health-related quality of life (HRQOL) of rheumatoid arthritis (RA) according to four different levels of functional severity. METHODS: A face-to-face interview survey was administered to patients with RA recruited at the Rheumatology Clinic of Seoul National University Hospital. Direct costs (medical costs [treatment, drug, private physiotherapy, traditional Chinese medicine, other alternative medicine], nonmedical costs [travel, dietary supplements, auxiliary device, home assistance]), indirect costs (productivity loss due to job loss and sick leave), and deterioration in the HRQOL of patients with RA were measured. Factors associated with the COI and the HRQOL were analyzed by using multiple regression and multivariate logistic regression. RESULTS: A total of 196 patients were enrolled for this study. As RA functional severity worsened, the total costs increased accordingly (class I: 4,230,204 Korean won, class II: 7,250,674 Korean won, class III: 8,046,434 Korean won, class IV: 8,206,215 Korean won). Direct costs also increased with the severity of the functional status, with a sharp decrease in class IV. The average HRQOL score was 0.49, showing an evident impact of RA severity (class I: 0.67, class II: 0.50, class III: 0.29, class IV: 0.23). Functional class and comorbidity were significant determinants of the COI and the HRQOL. CONCLUSION: Functional severity was a major factor associated with higher COI and lower HRQOL scores. Therefore, preventing the aggravation of functional severity is crucial for decreasing the COI and improving the HRQOL of patients with RA.

Evaluation of osteoarthritis induced by treadmill-running exercise using the modified Mankin and the new OARSI assessment system.

To apply the Osteoarthritis Research Society International (OARSI) assessment system to an osteoarthritis model, 44 Wistar rats were randomized into treadmill-running exercise or control group. At 6, 8, and 10 weeks, medial knee joints were histopathologically evaluated, and aggrecan neoepitope and TUNEL staining were performed. Cartilage changes in exercise group were histopathologically and histochemically compatible with early OA. Total modified Mankin system (MMS) scores were significantly higher at all time points (each P ≤ 0.01) in exercise than in control group. However, only tibial OARSI scores of runners were higher at 10 weeks (P < 0.05), although OARSI scores were found to be significantly correlated with MMS scores. Both total MMS (Spearman's coefficient ρ = 0.786) and OARSI scores (ρ = 0.443 for femoral; ρ = 0.604 for tibial) were significantly associated with the exercise duration. In conclusion, the OARSI system may not be sensitive to early OA changes induced by treadmill exercise.

Assessment of comparative pain relief and tolerability of SKI306X compared with celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, double-dummy, phase III, noninferiority clinical trial.

BACKGROUND: SKI306X, which consists of biologically active ingredients from Clematis mandsburica, Tricbosantbes kirilowii, and Prunella vulgaris, was developed and tested in preclinical trials in Korea. Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect, and that it can delay the destruction of cartilage in rheumatoid arthritis (RA). OBJECTIVE: The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA. METHODS: This study was a 6-week, multicenter, randomized, double-blind, double-dummy, Phase III, noninferiority clinical trial. Eligible patients were aged 18 to 80 years, had a history of RA with a disease duration of > or =3 months, and were functional American College of Rheumatology (ACR) class I, II, or III before entry. After a washout period of 2 weeks, patients were randomized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks. The primary end point was a change in patient assessment of pain intensity using a visual analog scale (VAS). The secondary end points were a 20% improvement in response rate as defined by the ACR (ACR20) and the frequency of rescue medication use. Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator. RESULTS: Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and randomized to 1 of 2 treatment groups. Ninety-one patients (10 male, 81 female; mean [SD] age, 52.13 [12.64] years; mean [SD] duration of RA, 9.08 [10.23] years; no. [%] of ACR class I, II, and III, 13 [14.29], 44 [48.35] and 34 [37.36] patients, respectively) received SKI306X 200 mg TID and 92 patients (10 male, 82 female; mean [SD] age, 51.78 [10.94] years; mean [SD] duration of RA, 8.78 [7.78] years; no. [%] of ACR class I, II, and III, 14 [15.22], 44 [47.83], and 34 [36.96] patients, respectively) received celecoxib 200 mg BID. An analysis of the change in reported pain intensity as determined by VAS (mm) score between baseline and week 3 (mean [SD], 13.64 [16.62] vs 14.45 [15.89]), and between baseline and week 6 (18.4 [20.8] vs 17.9 [19.1], respectively) suggested that SKI306X was not inferior to celecoxib. The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 (16/87 [18.4%] vs 24/87 [27.6%], respectively) and at week 6 (29/87 [33.3%] vs 29/87 [33.3%]). The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 (54/87 [62.1%] vs 47/87 [54.0%], respectively) or week 6 (57/87 [65.5%] vs 49/87 [56.3%]). Drug-related AEs were reported by 27 (29.7%) patients in the SKI306X group and 22 (23.9%) patients in the celecoxib group. The most frequent drug-related AEs were epigastric pain (9/91 [9.9%]) in the SKI306X group and glutamyltranferase elevation (4/92 [4.3%]) in the celecoxib group. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs. CONCLUSION: The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA.