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Background/Aims To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. Results The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. Conclusions Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

Background Rheumatoid arthritis interstitial lung disease (RA-ILD) is one of the most common complications of rheumatoid arthritis (RA) that severely impairs the quality of life and survival. Zang Bi Formula (ZBF) is mostly used in clinical practice for patients with recurrent occurrence of RA. However, its mechanism of action and efficacy in RA-ILD still remain unclear. Objective To investigate the therapeutic possibilities and potential mechanisms of the ZBF on RA and RA-ILD. Objective To investigate the therapeutic possibilities and potential mechanisms of the ZBF on RA and RA-ILD. Methods From January 2022 to March 2023, a total of 14 tumor necrosis factor alpha-transgenic (TNF-Tg) mice were randomly divided into Saline group and ZBF group, with 7 mice in each group. At the same time, 7 wild-type (WT) mice in the same litter were randomly selected as the control group (WT group). Intragastric administration of ZBF 1.4 g/mL with 0.2 mL per time was given to mice of ZBF group once a day, and those in the WT group and Saline group were given an equal amount of normal saline via intragastric administration. After the intervention for 8 weeks, hematoxylin&eosin (H&E) staining of mouse ankle tissues was performed to observe the inflammatory cell area. Alcian blue-orange and tartrate-resistant acid phosphatase (TRAP) staining was performed to observe the cartilage area and bone area ratio, as well as the osteoclast area, respectively. The area proportion of inflammatory cells, fibrosis and T-cell/B-cell proportion in mouse lung tissues were observed by H&E staining, Masson staining and immunofluorescence staining, respectively. Results Mice in the Saline group had significantly increased inflammatory cell infiltration, synovial hyperplasia, and ankle tissue destruction. Inflammation of the ankle joint was alleviated in the ZBF group. The proportion of inflammatory cells in the Saline group was significantly higher than that of the ZBF group and WT group, which was significantly higher in the ZBF group than that of the WT group (P

Background: People with inflammatory rheumatological conditions (IRCs) are at high risk of developing other conditions including cardiovascular disease (CVD) and mood disorders. Aim: To explore perspectives of people with IRCs and healthcare practitioners (HCPs) on the content and delivery of a review consultation aimed at identification and management of multiple long-term conditions (mLTCs). Design & setting: Semi-structured interviews and focus groups with people with IRCs and HCPs in primary and secondary care. Method: People with IRCs participated in individual semi-structured interviews by telephone or online platform. HCPs (including primary and secondary care clinicians) participated in online focus groups. Data were transcribed verbatim and analysed using inductive thematic analysis. Results: Fifteen people with IRCs were interviewed; three focus groups with HCPs were conducted. The following two main themes were identified: reflecting on the value of review consultations; and what would a new review look like? Overall, people with IRCs and HCPs reflected that access to reviews is inequitable, leading to duplication of reviews and fragmentation in care. People with IRCs, at times, had difficulty conceptualising reviews, especially when discussing their future risk of conditions. People suggested that preparation before the healthcare review could align patient and HCP agendas as part of a flexible and person-centred discussion. Conclusion: Any review introduced for people with IRCs must move beyond a ‘tick-box’ exercise. To gain maximum value from a review, preparation from both patient and HCP may be required alongside a person-centred approach while ensuring they are targeted at people most likely to benefit.

Abstract Introduction ABP 501 was an adalimumab (ADA) biosimilar approved for treating immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). In this retrospective study, we aimed to examine the treatment patterns of ABP 501 among patients with these IMIDs using German and French pharmacy claims databases. Methods Patients with RA, PsA, or AS who initiated ABP 501 between October 2018 and March 2020 and were observed continuously for ≥ 365 days both before and after ABP 501 initiation were included. Descriptive analyses of persistence and switch after ABP 501 discontinuation were conducted and reported for each disease cohort by prior use of ADA products (patients naïve to ADA or patients experienced with ADA). Results Median (95% confidence interval) persistence on ABP 501 was 9.4 (8.6–10.3), 10.2 (9.0–11.7), and 12.1 (11.0–13.1) months in German patients, and 11.7 (9.9–13.3), 7.1 (5.8–8.4), and 10.8 (9.6–11.9) months in French patients for RA, PsA, and AS, respectively. For patients who switched from ABP 501 to another targeted therapy during the first 12 months of follow-up, switching patterns varied between patients naïve to ADA and patients experienced with ADA in both Germany and France, with patients naïve to ADA switching most frequently to other targeted therapies including non-ADA tumor necrosis factor inhibitor (TNFi), non-TNFi biologic, or Janus Kinase inhibitor (JAKi) and patients experienced with ADA switching most frequently back to ADA reference product (RP). Conclusions Across three rheumatologic diseases, about half of patients persisted on ABP 501 at the end of 12 months after treatment initiation in both Germany and France. Patients experienced with ADA were more likely to switch back to ADA RP, regardless of indication and country, suggesting a possible nocebo effect. Future studies are warranted to understand reasons of discontinuation and switching.

Background: The attentive management of rheumatoid arthritis (RA) has attracted particular attention. The German 7-joint Ultrasound (US-7) is the first scoring system that combines bone erosions and soft tissue lesions in a single composite scoring system. This study aimed to assess the correlation between US-7 and Disease Activity Score Using 28 Joint Counts (DAS28) in clinically active RA patients. The efficacy of a novel ultrasound score-based system, the US-9 score (joints assessed with US-7 plus knees), was also compared with the standard US-7 score.Methods: All the RA patients referred to the outpatient rheumatology clinic of Ghaem Hospital, Mashhad, Iran, during 2019-2020 were included. 28 joints were clinically examined to calculate DAS28. Nine joints were assessed comprising the German US-7 plus knees using grayscale ultrasonography (GSUS) and power Doppler ultrasonography (PDUS). Retrieved data were analyzed by SPSS software, version 22. The Spearman Correlation test was used to find the correlation between DAS28 and ultrasonographic findings. The statistical significance level was set at P

Abstract Background To investigate whether baseline serum cartilage oligomeric matrix protein (COMP), patient characteristics, traditional cardiovascular disease (CVD) risk factors and disease activity over time predict CVD, in early rheumatoid arthritis (RA). Methods This study included patients with early RA ( 5.1) at two years was associated with increased risk of subsequent CVD [adjusted HR 2.58; 95% CI 1.10–6.04] and CAD. ESR and CRP at two years as well as cumulative disease activity over 2 years independently predicted CVD and CAD. Conclusion COMP may be a novel predictor of CVD and CAD in RA. Active disease two years after RA diagnosis, as well as cumulative disease activity, was associated with increased risk of CVD and CAD, independent of traditional CVD risk factors. Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA.

Background: Rheumatoid arthritis (RA) is a progressive inflammatory disease affecting the joints with a marked impact upon functional capacity of the patient. The working ability of RA patients can be preserved if the disease modifying antirheumatic drug (DMARD) therapy is initiated early in the course of disease. The objective of our study was to compare the disease activity variables in DMARD-naïve seropositive rheumatoid arthritis (SPRA) and seronegative rheumatoid arthritis (SNRA) patients and to determine correlations between the disease activity variables in RA. Methods: A cross-sectional study recruited n=90 patients from Rheumatology Clinic from May 2020 to October 2020. The rheumatoid factor (RF), anti-cyclic citrullinated peptide levels (ACCP), erythrocyte sedimentation rates (ESR) were clinically measured. Disease activity variables including the tender joint count (TJC), swollen joint count (SJC), health assessment questionnaire-disability index (HAQ-DI) and disease activity score of 28 joints (DAS28) were consistently calculated. Patients were divided into seropositive RA group and seronegative RA group, based on RF and ACCP. Chi squared test and Pearson correlation were applied, p≤0.05 was considered statistically significant. Results: High HAQ-DI and DAS28-ESR scores were found in SPRA than in the SNRA patients and were statistically significant (p=0.000, p=0.054). TJ-28 and SJ-28 counts were higher in SPRA but were not statistically significant. There was a significant correlation of DAS28 with TJ-28 (r=0.816, p-value = 0.000), with SJ-28(r=0.801, p-value = 0.000) and HAQ-DI (r=0.517, p-value = 0.000). Conclusion: Evaluation of inflammatory markers and functional disability was found significant (p=0.000) in determining the disease activity compared to presence of autoantibodies in DMARD naïve RA patients.

ABSTRACT Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren’s syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

Rheumatoid arthritis (RA) is a refractory autoimmune disease with chronic and systemic characteristics, however, the pathogenesis of this disease has not been fully defined. Autophagy is a metabolic process that exists in eukaryotic cells and maintains normal physiological activities and cell homeostasis. Dysregulation of autophagy is related to the occurrence and development of various diseases such as RA. The databases of CNKI, Wanfang Data, VIP, PubMed, Web of Science, Elsevier, etc. were searched for the literature related to autophagy in RA pathogenesis. The role of autophagy in the pathogenesis of RA was summarized in terms of maintaining synovial inflammation (improving anti-apoptosis rate of synovial cells and regulating the phenotype transformation of synovial cells), promoting bone destruction (participating in osteoclastogenesis and regulating chondrocyte apoptosis) and disrupting immune system homeostasis (regulating the activation and maturation of immune cells, participating in the presentation of citrullinated proteins, and inducing carbamoylation of proteins), in order to provide basis and reference for the pathogenesis research and treatment of RA.

Abstract Background Traditionally rheumatoid arthritis (RA) trials classify patients as responders and non-responders; they ignore the potential range of treatment responses. Group Based Trajectory Models (GBTMs) provide a more refined approach. They identify patient subgroups with similar outcome trajectories. We used GBTMs to classify patients into subgroups of varying responses and explore factors associated with different responses to intensive treatment in a secondary analysis of intensive treatment in the TITRATE clinical trial. Methods The TITRATE trial enrolled 335 patients with RA: 168 patients were randomised to receive intensive management, which comprised monthly assessments including measures of the disease activity score for 28 joints (DAS28), treatment escalation when patients were not responding sufficiently and psychosocial support; 163 of these patients completed the trial. We applied GBTMs to monthly DAS28 scores over one year to these patients who had received intensive management. The control group had standard care and were assessed every 6 months; they had too few DAS28 scores for applying GBTMs. Results GBTMs identified three distinct trajectories in the patients receiving intensive management: good (n = 40), moderate (n = 76) and poor (n = 47) responders. Baseline body mass index (BMI), disability, fatigue and depression levels were significantly different between trajectory groups. Few (10%) good responders were obese, compared to 38% of moderate, and 43% of poor responders (P = 0.002). Few (8%) good responders had depression, compared to 14% moderate responders, and 38% poor responders (P

Abstract Objective The aim of this prospective cross sectional study was to evaluate the cranial structure and condylar asymmetry of adult patients with rheumatoid arthritis (RA) diagnosed after 25 years of age compared to a healthy adult control group. Methods Eighteen adult patients (57.4 ± 11.4 years) with RA were compared with a control group. Cephalometric analysis and the Habets method for the calculation of the condylar asymmetry were used. The main cephalometric data investigated were focused on the diagnosis of hyperdivergent cranial structure (NSL/ML, NL/ML), backwards rotation of the mandible (Fh/ML), short vertical ramus (Ar:Go), steep mandibular plane (ML/Oc). Results The cephalometric data considered were not significantly different in the RA vs controls except for the steepness of the occlusal plane (NL/Oc), which was steeper in the patients group (P

Background/Aim. Peripheral neuropathy (PN) in systemic connective tissue diseases (SCTDs) represents the apparent disease complications or initial manifestations of clinically undiagnosed conditions. The aim of the study was to identify neuropathies (Ns) and their prevalence, point out the diagnostic significance of some electrophysiological (EP) parameters in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc), and establish their association with disease activity (DA) and disease duration (DDu). Methods. A prospective study was conducted at the Rheumatology Clinic of the Institute for Treatment and Rehabilitation “Niška Banja” over a three-year period. The study included 157 patients in total, of whom 61 had R A, 4 0 had SLE, and 56 had SSc. The following parameters were analyzed: age, gender, DDu, course of the disease, and DA index. Moreover, clinical, rheumatological, and neurological examinations, as well as neurology tests, nerve conduction studies (NCS), and laboratory analyses, were also conducted. Results. In the studied population, we were able to identify various forms of Ns (in 28.7% of patients) by NCS. In all three groups, the most prevalent type of Ns was axonal (23.6%), sensorimotor (18.5%), and polyneuropathy (23.6%). There was a significant association between DA and the occurrence of Ns (p < 0.001) in the total population. The most important EP parameter was the sensory nerve action potential amplitude of nervus peroneus superficialis [in 70 (44.6%) patients] and nervus suralis [in 35 (22.3%) patients], and compound muscle action potential amplitude of nervus peroneus [in 32 (20.4%) patients]. DDu in all three groups was longer in the population of patients with Ns. Conclusion. Ns are most common in patients with longer DDu and higher DA. The EP method is important in detecting Ns, especially in the early detection of subclinical forms of Ns and the prevention of disease complications.

Background/Aim. Depression, as a common comorbidity in patients with rheumatoid arthritis (RA), has been found to affect the disease diagnosis and treatment response. Accordingly, the aim of the study was to investigate the occurrence of depressive symptoms among patients with RA and the association between RA and depression. Methods. The cross-sectional study included 69 patients with RA. The depressive symptoms in patients with RA were assessed using the Beck Depression Inventory (BDI), and RA activity was measured by Disease Activity Score-28 for RA with erythrocyte sedimentation rate (DAS28-ESR) and Clinical Dis-ease Activity Index (CDAI). Results. It was found that 42% of respondents reported having depressive symptoms of different severity, among which the majority (23.2%) presented with mild symptoms. A mild positive correlation was found between the BDI and the DAS28-ESR (r = 0.39 p = 0.001), as well as between the BDI and the CDAI (r = 0.40 p = 0.001). Place of residence (t = -2.14 p = 0.03) and employment status (t = -2.81 p = 0.00) associated with depressive symptoms were also found to have statistically significant differences within the group of respondents. In addition, age had a positive correlation with the disease activity, as well as the place of residence and employment status. Conclusion. It has been observed that depressive symptoms in patients with RA were associated with disease activity, employment status, and place of residence. Therefore, there is an important need for integrating rheumatologic and mental health services for future research toward a better understanding of both depression and RA.

Background/Aim. Rheumatoid arthritis (RA) represents an independent risk factor for the development of cardiovascular (CV) disease (CVD). Early detection of atherosclerotic changes is of tremendous importance in the prevention of CV events. An increase in the carotid artery intima-media thickness (cIMT) is considered a sensitive marker of early subclinical atherosclerosis. The aim of our investigation was to assess the cIMT, the number and type of carotid plaques (CPs), and the severity of carotid artery stenosis in RA patients. Furthermore, we investigated the correlation between all the above-mentioned parameters and disease duration and activity. Methods. The research included 92 participants, of which 58 were patients with RA, and the remaining 34 participants were healthy individuals (control group). In patients with RA, clinical examination and laboratory findings were used for assessing disease activity. All participants underwent a color Doppler ultrasound examination of the carotid arteries with a linear probe in order to assess cIMT, the number and type of CPs, as well as the se-verity of stenotic lesions. Results. The mean cIMT in RA patients was statistically significantly higher compared to the control group (0.8 ± 0 .2 mm vs. 0.7 ± 0.2 m m; p < 0.01). CPs were found in 34 out of 58 RA patients (58.6%) and 4 out of 34 (11.8%) participants in the control group (p < 0.001). The number of CPs per patient was significantly higher in the RA group compared to the control group (1.4 ± 0.9 vs. 0.2 ± 0.4; p < 0.001). The cIMT, the presence and number of CPs, and the severity of carotid artery stenosis were not statistically significantly related to disease activity. There was a statistically significant direct correlation between the duration of RA and the percent-age of carotid arterial stenosis (r = 0.320, p = 0.034). Conclusion. The cIMT and the presence and number of CPs per patient were significantly higher in RA patients. More-over, there was a positive correlation between RA disease duration and the severity of carotid artery stenosis. This study showed that RA represents an independent risk factor for an increase in cIMT and the development of sub-clinical atherosclerosis.

Background/Aims This study aims to evaluate the incidence of malignancy in patients with rheumatoid arthritis (RA) and to investigate risk factors for such in a nationwide, population-based cohort. Methods In a large, prospective, observational cohort study, 5,077 patients with RA were enrolled from July 2009 to December 2011 and followed until February 2017. Standardized incidence ratios (SIRs) for malignancy were calculated using age- and sex-specific cancer rates in the Korean general population. Poisson regression was used to identify the risk of incident malignancy. Results The cohort included 5,023 participants with RA contributing 16,689 person-years of follow-up. A total of 148 malignancies were recorded. The risks of stomach cancer (SIR, 0.41; 95% confidence interval [CI], 0.21 to 0.74), colon cancer (SIR, 0.13; 95% CI, 0.03 to 0.37), and lung cancer (SIR, 0.35; 95% CI, 0.14 to 0.72) were lower in RA patients than in the general population. Poisson regression modeling demonstrated that the malignancy risk was more than two-fold greater in patients with thyroid disease than in those without thyroid disease. Hydroxychloroquine therapy was associated with a reduced risk (relative risk, 0.39; 95% CI, 0.189 to 0.801) of malignancy development. Conclusions The overall risk of malignancy in patients with RA is decreased relative to in the general population. In particular, stomach, colon, and lung cancers in Korean RA patients are less common, while brain and central nervous system cancers in male RA patients are more frequent. The patients with thyroid disease and longer RA disease duration were at increased risk for developing malignancy, while hydroxychloroquine users were at lower risk.

ABSTRACT OBJECTIVE This work aims to analyze the quantity and expenses related to biological drugs used for the treatment of rheumatoid arthritis (RA) in outpatient public care within the Brazilian Unified Health System (SUS). METHODS It is a cross-sectional descriptive study based on secondary data from a historical series, referring to the purchase, volume, and the number of patients treated with different biological drugs (infliximabe, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab, and certolizumab pegol) for RA treatment in outpatient care from 2012 to 2017. The data were extracted from the SUS Outpatient Information System database-SIA/SUS and included ten drugs used for RA treatment. The study assessed the quantity and expenditure of these drugs, the number of RA patients treated, and the expenditure by RA subtypes. The National Broad Consumer Price Index was used to adjust the expenditures for December 2017. RESULTS The Ministry of Health allocated approximately $500 million to provide about 2 million units of biological drugs for RA patients from 2012 to 2017. The supply of adalimumab 40 mg and etanercept 50 mg accounted for 68.3% of the total expenditure. The subtypes “other rheumatoid arthritis with rheumatoid factor” (ICD-10 M05.8), “rheumatoid arthritis without rheumatoid factor” (ICD-10 M06.0), and “Felty’s syndrome” (M05. 0) represented 84.5% of the total expenditures. The proportion of patients treated with biological drugs increased by 33.0%. There was a significant 83.0% increase in the number of patients using biological drugs compared to the overall number of RA patients treated during the study period. CONCLUSIONS The results obtained allow us to draw a more recent profile of expenditure on RA treatment and indicate trends in the use of biological drugs for this condition, generating data that can support management decisions in public health policies.

Abstract Background There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions, to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score. Methods RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test and Cochrane-Q test respectively, including the comparison of palmar vs. dorsal regions (chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response means (SRM)/linear regression. Analyses were also performed separately for early and established RA. Results A total of 435 patients (N = 138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p ≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (p

Abstract Background Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. Methods Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. Results Of the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255–0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235–0.797), breast cancer (0.146; 0.045–0.474), and genitourinary cancer (0.220; 0.059–0.820). Conclusions The use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a ubiquitously expressed intracellular signal transduction pathway involved in cell proliferation, differentiation, apoptosis, immune regulation and other biological processes. Existing evidence indicates that continuous activation of this signaling pathway is closely related to the pathogenesis and clinical manifestations of many autoimmune rheumatic diseases. We reviewed the latest advances in mechanisms of JAK/STAT signal transduction, and the roles of the pathway in development of autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, and gout, suggesting that JAK/STAT signaling pathway may be a therapeutic target for autoimmune rheumatic diseases, which may offer new ideas and directions for clinical treatment.

Background/Aim. Rheumatoid arthritis (RA) is accompanied by numerous comorbidities, among which depression and anxiety (D/A) occupy a significant place. The aim of the study was to determine the prevalence of D/A in RA patients and the relationship with their quality of life (QoL). Methods. The study included RA patients treated at the Rheumatology Clinic of the Military Medical Academy in Belgrade, Serbia in the period from May to November 2016. Disease activity was assessed by the Disease Activity Score 28-SE (DAS28-SE). D/A was determined using the Hospital Anxiety and Depression Scale (HADS) questionnaire and European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) questionnaire Question 5. Three questionnaires were used to assess QoL: the general RAND 36-item Health Survey 1.0 (RAND36), the specific Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) and EQ-5D-3L. Results. Based on the HADS questionnaire, the prevalence of depression was 52% with the average HADS score value of 7.6 ± 3.2, while the prevalence of anxiety was 32% with the mean HADS score value of 5.8 ± 3.8. Question 5 of the EQ-5D questionnaire showed that the prevalence of D/A was 77.4%, of which 71.7% of patients had moderate D/A, while 5.7% of patients had severe D/A. Impairment in all the domains of QoL was found in tested patients, as assessed by all three questionnaires. The RAQoL questionnaire showed moderate QoL impairment, with a score value of 15.5 ± 7.9. The EQ-VAS score value was 58.6 ± 16.0, while the EQ-5D index was 0.6 ± 0.3. Univariate linear regression produced a statistically significant negative predictive value of QoL for the presence of D/A. Multivariate linear regression showed a statistically significant independent negative predictive value of QoL, as assessed by the RAQoL questionnaire (p = 0.010) and the mental QoL component of the RAND 36 questionnaire (p = 0.030) for the degree of depression. Conclusion. In RA patients, there is a significant prevalence of D/A as well as impairment of QoL in all domains. The tests performed have shown that QoL has a statistically significant negative predictive value for the presence of D/A.

Introduction. Mucormycosis is a life-threatening opportunistic infection whose incidence has significantly risen during the last two decades. The gastrointestinal form is very rare, with the stomach as the most common site of infection, followed by the colon and ileum. Risk factors include uncontrolled diabetes mellitus, corticosteroid use, and organ transplantation. We report a patient with a history of rheumatoid arthritis who has developed gastrointestinal mucormycosis. To the best of our knowledge, this is the first such case reported in the literature. Case report. A 53-year-old female patient with a prior medical history of rheumatoid arthritis was admitted to the hospital due to persisting diarrhea. Physical examination revealed diffuse abdominal tenderness to palpation without meteorism and peritoneal signs. Laboratory results demonstrated systemic inflammation, so antibiotic therapy was administered. Abdominal computed tomography findings revealed inflammation of the rectum and the left colon. Colonoscopy findings were indicative of Crohn’s disease. Additionally, the patient had developed profuse rectal bleeding and consequently underwent emergency surgery. Subtotal colectomy with ileostomy and partial gastrectomy was performed. The patient’s condition rapidly worsened after the operation, and she died due to multi-organ failure. Histologic findings of resection specimens discovered chronic active colitis and extensive gastric necrosis associated with dense mixed inflammatory infiltration and numerous non-septate and 90-degree branching hyphae. Diagnosis of invasive gastric mucormycosis was obtained, but unfortunately, several days after the patient’s death. Conclusion. It is very important to obtain high awareness among clinicians of this deadly infection to achieve a prompt diagnosis and effective therapy.

Abstract Background Drug coverage policies that incentivize switching patients from originator to biosimilar products may result in significant health care savings. Our study aimed to detect early impacts on health services utilization following a mandated switch from originator to biosimilar etanercept in British Columbia (BC), Canada. Methods We conducted a prospective, population-based cohort study using linked administrative health data from BC (2010–2020). The policy cohort consisted of patients with inflammatory arthritis who used originator etanercept in 2019, prior to BC’s Biosimilars Initiative switching policy. Three historical cohorts included patients with inflammatory arthritis who used originator etanercept in the years 2016, 2017, and 2018. We compared the daily cumulative incidences of drug refills and outpatient and inpatient services between the policy and historical cohorts. A likelihood ratio sustained (≥ 31 days) at 7.1 or higher compared with the null hypothesis was chosen a priori as a threshold for a potential impact of the policy. Results Each cohort contained between 1694 and 1963 patients. We detected several potential impacts: 1) a transient increase in etanercept refills between months three and eight (cumulative incidence difference of + 3.0%); 2) an anticipated increase in visits to physicians of any specialty between months three and eight (+ 2.6%); and 3) an anticipated increase in visits to a rheumatologist from the end of month three onwards (+ 12.8%). The policy had no impact on incidences of switching to a different biologic antirheumatic drug, visits to emergency departments, or admissions to hospitals. Conclusions Only transient and/or anticipated increases in drug refills and physician visits were observed during the study period. Additional research on clinical outcomes is recommended to strengthen the evidence that no long-term unintended negative health impacts are associated with BC’s Biosimilars Initiative [switching policy].

ABSTRACT Rheumatoid arthritis (RA) is an autoimmune inflammatory and heterogeneous disease that affects several systems, especially the joints. Among the extra-articular manifestations of RA, pleuropulmonary involvement occurs frequently, with different presentations, potentially in all anatomic thoracic compartments, and may determine high morbidity and mortality. The most common pleuropulmonary manifestations in patients with RA include interstitial lung disease (ILD), pleural disease, pulmonary arterial hypertension, rheumatoid lung nodules, airway disease (bronchiectasis and bronchiolitis), and lymphadenopathy. Pulmonary hypertension and ILD are the manifestations with the greatest negative impact in prognosis. HRCT of the chest is essential in the evaluation of patients with RA with respiratory symptoms, especially those with higher risk factors for ILD, such as male gender, smoking, older age, high levels of rheumatoid factor, or positive anti-cyclic citrullinated peptide antibody results. Additionally, other etiologies that may determine tomographic pleuropulmonary manifestations in patients with RA are infections, neoplasms, and drug-induced lung disease. In these scenarios, clinical presentation is heterogeneous, varying from being asymptomatic to having progressive respiratory failure. Knowledge on the potential etiologies causing tomographic pleuropulmonary manifestations in patients with RA coupled with proper clinical reasoning is crucial to diagnose and treat these patients.

Abstract Background Certain risk alleles associated with autoantibody-positive rheumatoid arthritis (RA) have been linked to poorer prognoses. In patients with autoantibody-positive RA, abatacept shows differential efficacy to tumor necrosis factor inhibitors. Our aim was to investigate the relationship between clinical response to abatacept and to adalimumab and presence of risk alleles encoding human leukocyte antigen (HLA)-DRB1 shared epitope (SE) in RA. Methods In this head-to-head study, biologic-naïve adults with early (≤ 12 months), moderate-to-severe RA and inadequate response to methotrexate (MTX-IR), autoantibody-positive for both anti-cyclic citrullinated peptide 2 and rheumatoid factor, were randomized 1:1 to receive subcutaneous abatacept 125 mg weekly or subcutaneous adalimumab 40 mg every 2 weeks for 24 weeks with stable, weekly oral MTX. An open-label period to 48 weeks followed, during which adalimumab-treated patients were switched to abatacept. Patients were genotyped for HLA-DRB1 alleles and classified as SE-positive (≥ 1 SE allele) or SE-negative (no SE alleles). Efficacy was assessed at weeks 24 and 48. Results Forty patients each received abatacept (9 SE-negative, 30 SE-positive, one unknown) or adalimumab (9 SE-negative, 31 SE-positive). Mean age and disease duration were 46.0 years and 5.5 months, respectively. At week 24, a greater percentage of abatacept patients achieved 50% improvement in ACR criteria (ACR50) compared with adalimumab patients (73% vs 45%, respectively) and estimate of difference (95% confidence interval [CI]), 28 (5, 48). In SE-positive patients, ACR50 estimate of difference (95% CI) was 32 (7, 55). During the open-label period, responses were sustained in the abatacept non-switch group and showed trends toward further improvement in the adalimumab-to-abatacept switch group at week 48, in both the overall and the SE-positive subpopulation. No new safety signals were identified. Conclusions In MTX-IR patients with early, autoantibody-positive RA, abatacept resulted in numerically higher efficacy responses versus adalimumab after 24 weeks, with more pronounced treatment differences in SE-positive patients. After 48 weeks, responses were sustained in patients who continued abatacept while those who switched to abatacept showed further clinical improvement, overall, and in SE-positive patients. This supports co-stimulation blockade as an effective treatment strategy for patients with early, autoantibody-positive RA, particularly among SE-positive patients. Trial registration NIH US National Library of Medicine, NCT02557100 . Registered on September 23, 2015.

Background/Aims This study was performed to undertake cross-cultural adaptation and validation of the Educational Needs Assessment Tool (ENAT) in rheumatoid arthritis (RA) for use in Korea. Methods The study involved two main phases: cross-cultural adaptation of the ENAT from English into Korean, and validation of the Korean ENAT. The first phase followed the established process of cross-cultural adaptation of self-report measures, and in the second phase, the Korean ENAT data were analyzed using the Rasch measurement model. Fit to the model was determined using the observed data infit and outfit statistics. Additional tests of validity included unidimensionality and internal consistency. Results Adequate conceptual equivalence was achieved following the adaptation process. A total of 123 patients completed the Korean ENAT. The mean age was 46.7 ± 12.3 years and the majority of patients (81.3%) were female. Thirty-five of the 39 items gave good fit to the model. The four items deviating from the model had infit and outfit > 1.50. The item separation index (5.26) and item reliability index (0.97) provided evidence for good reliability of items. All seven domains of the Korean ENAT fit the Rasch model. The internal consistency of the Korean ENAT was high, and unidimensionality was confirmed (person separation index, 3.41; reliability index, 0.92; item separation index, 16.82; reliability index, 1.00). Conclusions Using the standard procedure for cross-cultural adaptation, the ENAT has been adapted into Korean, and Rasch analysis has confirmed the construct validity, reliability, and unidimensionality of the Korean ENAT.

Abstract Background To explore the prevalence of bone loss among patients with rheumatoid arthritis (RA) and healthy controls (HC) and further explored the risk factors for osteopenia and osteoporosis of RA patients. Methods A cross-sectional survey was undertaken in four hospitals in different districts in South China to reveal the prevalence of bone loss in patients. Case records, laboratory tests, and bone mineral density (BMD) results of patients were collected. Traditional multivariable logistic regression analysis and two machine learning methods, including least absolute shrinkage selection operator (LASSO) and random forest (RF) were for exploring the risk factors for osteopenia or osteoporosis in RA patients. Results Four hundred five patients with RA and 198 HC were included. RA patients had lower BMD in almost BMD measurement sites than healthy controls; the decline of lumbar spine BMD was earlier than HC. RA patients were more likely to comorbid with osteopenia and osteoporosis (p for trend

ABSTRACT Objective: To analyze the cervical sagittal parameters of patients with rheumatoid arthritis (RA) and compare them with the parameters obtained from healthy patients in a sample of the Brazilian population. Methods: Epidemiological data were collected and 72 radiographs of the cervical spine in the sagittal plane were evaluated by measuring the cervical sagittal parameters COG-C7 (distance measured between the center of gravity of the head and the C7 plumb line -cranial offset), C2-C7 lordosis (vertebrae from C2 to C7), T1S (T1 slope), TIA (thoracic inlet angle) and NT (neck tilt). Statistical analysis was performed using the Student’s t and chi-square tests. Results: The TIA and NT values in the RA group were 88.8° ± 12.6° and 54.5° ± 9.3°, respectively, while for the control group, they were 77.7° ± 7.9° and 50.5° ± 7.7°, respectively, the RA group values being statistically higher than the control group values (p

ABSTRACT BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease with higher prevalence among women aged between 30 and 50 years and general prevalence of 1% worldwide. Interventions promoting improvement of quality of life for individuals with RA are required. Tai Chi appears to be a low-cost alternative, with studies showing positive results from this technique. However, regarding aspects of RA such as pain and sensitivity, studies remain inconclusive. OBJECTIVES: To compare the effectiveness of the Tai Chi method for treating patients diagnosed with rheumatoid arthritis, among systematic reviews. DESIGN AND SETTING: Overview of systematic reviews with Cochrane and non-Cochrane methodology. METHODS: Systematic reviews involving quasi-randomized and randomized clinical trials (RCTs) on use of Tai Chi, with no restrictions regarding the date and language of publication, were included. RESULTS: Three systematic reviews were included. The effects of Tai Chi associated with education and stretching exercises versus education and stretching were evaluated in these reviews. They showed that improvements in the variables of mood, depression and functional index were associated with use of Tai Chi. CONCLUSIONS: The findings suggest that clinical improvement was achieved, although not statistically significant with regard to pain and disease pattern, as assessed using the ACR20 measurement. Improvements relating to disability and quality of life were also seen. There was a low level of evidence and therefore caution in data analysis is recommended. The three studies included showed poor reliability for providing an accurate and complete summary of use of Tai Chi among people diagnosed with rheumatoid arthritis. PROSPERO: CRD42019125501.

ABSTRACT Objective To evaluate the therapeutic response (functionality) and its associated factors in patients on biological drugs on the Public Health System for treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Methods An open prospective cohort was carried out from 2011 to 2019, in Belo Horizonte (MG). Functionality was assessed using the Health Assessment Questionnaire Disability-Index at baseline, and after 6 and 12 months of follow-up. Factors associated with poor functionality were identified through logistic regression. Results The median Health Assessment Questionnaire Disability-Index at baseline was 1.5 (interquartile range of 0.8-1.9), with poor functionality observed in patients with rheumatoid arthritis. Improved functionality was seen at 6 months of treatment for the three diseases. The predictors of poor functionality at 6 months for psoriatic arthritis and ankylosing spondylitis were female sex, low education levels, and high disease activity; and for rheumatoid arthritis and psoriatic arthritis were female sex, advanced age, and high disease activity. In 12 months, the three diseases had predictors of worse functionality: female sex, low education, and high disease activity. Conclusion There was a significant improvement in functionality during the follow-up, with better response at 6 months of treatment. Poor functionality was observed in older, female patients, with low education and high disease activity.

Objective: To determine the diversity of microbiota in the sub-gingival fluids from periodontitis and rheumatoid arthritis (RA) patients and to know the relationship of microbiota abnormalities between periodontitis and RA. Material and Methods: Samples were collected from sub-gingival fluids of nine participants by swabbing technique. The participants were divided into 3 groups, namely the control (not periodontitis and RA), periodontitis, and RA. The total number of bacteria was calculated by using direct culture in serial dilution by applying the total plate count method. Isolation of microbiota was conducted by pour plates and incubated in an anaerobic jar. The bacterial diversity was performed by Simpson index and DNA Isolation. Results: There were differences in the concentration of sub-gingival fluids bacteria in the control group with the periodontitis and RA group. The microbiota composition profiles were different for each group. The bacterial isolate 4, 5 and 22 were found in all groups, while isolate 14 was assumed to be related to the metabolic pathway in microbiota abnormalities associated with disease progression. Conclusion: The Simpson index has a value >0.61 with high bacterial dominance; however, the diversity of microbiota is at a low level of diversity. We assumed that isolate 14 was associated with development of RA disease.

Abstract Background Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune condition characterized by joint synovial inflammation. Current treatments include methotrexate (MTX), biologic agents, and Janus kinase (JAK) inhibitors. However, these agents are not efficacious in all patients and there are concerns regarding side effects and risk of infection as these treatments target immune-related pathways. Overexpression and activation of integrin alpha-9 (α9) on fibroblast-like synoviocytes are associated with RA disease onset and exacerbation. The humanized immunoglobulin G1 monoclonal antibody ASP5094 was designed to inhibit human α9 and is currently under investigation for the treatment of RA. Methods This phase 2a, multicenter, randomized, placebo-controlled, double-blind, parallel-group study (NCT03257852) evaluated the efficacy, safety, and biological activity of intravenous ASP5094 10 mg/kg in patients with moderate to severe RA that was refractory to MTX. Patients received ASP5094 or placebo every 4 weeks for a total of three administrations. Both treatment groups used concomitant MTX. The primary efficacy endpoint was the proportion of patients who responded per American College of Rheumatology 50% improvement using C-reactive protein (ACR50-CRP) after 12 weeks of treatment. Biological activity of ASP5094 was assessed via pharmacokinetics and pharmacodynamics of known downstream effectors of α9. Safety was also assessed. Results Sixty-six patients were enrolled and randomized to placebo (n = 33) or ASP5094 (n = 33). In the primary efficacy analysis, ACR50-CRP response rates were 6.3% and 18.2% at week 12 in the ASP5094 and placebo groups, respectively; a difference of − 11.9, which was not significant (2-sided P value = 0.258). No trends in ACR50 response rates were observed in subgroups based on demographics or baseline disease characteristics, and no significant differences between placebo and ASP5094 were identified in secondary efficacy or pharmacodynamic endpoints, despite achievement of target serum concentrations of ASP5094. Most treatment-emergent adverse events were mild to moderate in severity, and ASP5094 was considered safe and well tolerated overall. Conclusion Although no notable safety signals were observed in this study, ASP5094 was not efficacious in patients with moderate to severe RA with an inadequate response to MTX. Trial registration ClinicalTrials.gov, NCT03257852 . Registered on 22 Aug. 2017

Abstract Background Studies have demonstrated that seropositive patients with rheumatoid arthritis (RA) are susceptible to cardiovascular diseases (CVDs). In this study, we aimed to determine the association of autoantibodies with the echocardiographic parameters of systolic and diastolic dysfunction in such patients. Methods In this cross-sectional study, we evaluated patients with RA who were referred to our clinic from October 2017 to August 2018. After the exclusion of patients with concomitant CVD, all patients underwent transthoracic echocardiography and measurement of plasma autoantibodies. Moreover, possible confounders—including medications, CVD risk factors, Framingham risk score, disease activity score-28, duration of disease, simple disease activity index, and functional status—were assessed. Results We studied 135 patients with RA (mean age = 52.3 years; 111 (82.2%) females). We had missing data rates of up to 8.9% for some characteristics. E velocity was inversely correlated with rheumatoid factor (P = 0.009). Furthermore, the plasma levels of anti-citrullinated protein and anti-modified citrullinated vimentin (anti-MCV) antibodies were negatively correlated with left ventricular ejection fraction (LVEF) (P = 0.019 and P

Background/Aims Safety for tumor necrosis factor inhibitors (TNFi) in cancer has been focused on risk of incident malignancies, but studies on prognostic effects have been scarce. We determined survival and recurrence rates at 1, 2, and 5 years after cancer diagnosis in patients with and without concurrent TNFi use. Methods Chart reviews were performed between 1996 and 2015 at the VA North Texas Healthcare System. Cases were patients with inflammatory disease, concomitant malignancy, and TNFi use while controls were patients with inflammatory disease, concomitant malignancy but no TNFi use. Cases and controls were matched for type of malignancy. Analysis was performed with log-rank tests on Kaplan-Meier curves. Results Thirty-six cases and 72 controls were identified. For cases, survival at 1, 2, and 5 years were 32 (89%), 31 (86%), and 29 (81%) compared to 63 (90%), 61 (87%), and 51 (73%) for the control group (P=0.985). For cases, recurrence rates at 1, 2, and 5 years were 3 (8%), 5 (14%), and 6 (17%) compared to 2 (3%), 5 (7%), and 7 (10%) for the control group (P=0.158). Conclusions Our findings suggest TNFi may be safely used in select inflammatory disease patients with concurrent cancer if therapy is needed for proper disease control. However, case-by-case consideration in conjunction with an oncologist is recommended while considering the apparent safety of TNFi for patients suffering from active inflammatory diseases despite having a concomitant malignancy.

Abstract Background Rheumatoid arthritis (RA) is an inflammatory and chronic autoimmune disease that leads to muscle mass loss and functional capacity impairment, potentiated by physical inactivity. Despite evidences demonstrate neuromuscular impairments in RA patients, aging effects may have masked the results of similar previous studies. The aim of study was to verify (i) the effects of RA on functional capacity and muscle properties in middle-aged patients and (ii) the association between age, clinical characteristics, quadriceps muscle properties and functional capacity. Methods Thirty-five RA women and 35 healthy age-matched women were compared with the following outcomes: (i) physical activity level through the International Physical Activity Questionnaire (IPAQ); (ii) timed-up and go (TUG) test; (iii) isometric knee extensor muscular strength; and (iv) vastus lateralis muscle activation and muscle architecture (muscle thickness, pennation angle and fascicle length) during an isometric test. An independent Student t-test and partial correlation (controlled by physical activity levels) were performed, with p

Background/Aims Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. Methods Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. Results The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. Conclusions Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.

Abstract Background Joint replacements continue to occur during a rheumatoid arthritis (RA) patient’s lifetime despite significant advances in available treatment options. The purpose of this study was to examine and quantify synovitis in surgically operated joints by ultrasound (US) in RA patients starting a new therapeutic agent. Methods RA subjects were enrolled in either tocilizumab or tofacitinib open-label, investigator-initiated trials and were assessed by ultrasound. In a subset of RA patients with joint replacements and/or operations of joint areas (OJA; e.g. joint arthroscopies, fusions, and synovectomies), joint-level scores of synovitis were compared between replaced joints, OJAs, and native joints. Joint-level synovitis was measured by grayscale (GSUS (0–3)) and power Doppler (PDUS (0–3)) at baseline and follow-up (3–6 months). McNemar’s test or Wilcoxon signed rank test utilized the mixed effects ordinal logistic regression models. Results Twenty RA patients had a total of 25 replaced joints and 24 OJA. All replaced joints had GSUS> 1 and 92% had PDUS> 1 at baseline, while OJA and native joints had lower evidence of GSUS> 1 (37.5, 38% respectively) and PDUS> 1 (45.8, 62% respectively). GSUS and PDUS semiquantitative scores improved significantly with treatment in replaced joints (p = 0.01, p = 0.007), and native joints (p

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthritis, and the complex interaction and activation of innate and adaptive immune cells are involved in RA pathogenesis. Mast cells (MCs) are one of the tissue-resident innate immune cells, and they contribute to RA pathogenesis. In the present review, the evidence of the pathologic role of MC in RA is discussed based on human and animal data. In addition, the potential role of MC in RA pathogenesis and the research area that should be focused on in the future are suggested.

Background/Aims The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Biological disease-modifying antirheumatic drugs (bDMARDs) are highly effective agents for the treatment of inf lammatory arthritis; however, they also possess a potential risk for serious infection. Recently, with the rapid expansion of the bDMARDs market in Korea, reports of serious adverse events related to the agents have also increased, necessitating guidance for the use of bDMARDs. Current work entitled, “Expert consensus for the use of bDMARDs drugs for inflammatory arthritis in Korea,” is the first to describe the appropriate use of bDMARDs in the management of inflammatory arthritis in Korea, with an aim to provide guidance for the local medical community to improve the quality of clinical care. Twelve consensus statements regarding the use of bDMARDs for the management of rheumatoid arthritis and ankylosing spondylitis were generated. In this review, we provide detailed guidance on bDMARDs use based on expert consensus, including who should prescribe, the role of education, indications for use, and monitoring strategies for safety.

Abstract The authors report a case of mobile and painful nodules on the bilateral plantar surface of a female patient referred by the rheumatology service, where she was being followed-up for rheumatoid arthritis. A nodule excision was performed for differential diagnosis and symptom relief; the histopathological analysis was compatible with a rheumatoid nodule. Although rheumatoid nodules are a common manifestation of rheumatoid arthritis, exclusive plantar involvement is seldom described in the literature.

Background/aims To examine the association between rheumatoid arthritis (RA) and periodontitis or tooth loss. Methods The study used data from the fifth and sixth Korea National Health and Nutrition Examination Surveys conducted from 2010 to 2015. RA was defined as participant-reported physician-diagnosed RA that was being treated. Periodontitis and the number of natural teeth were determined by dental examination. Periodontitis was defined according to the community periodontal index (periodontal probing depth ≥ 4 mm). The association between RA and periodontitis or tooth loss was examined after controlling for confounding variables (e.g., age, smoking status, socioeconomic status, dental caries, frequency of toothbrushing, body mass index, alcohol consumption, and diabetes) in men and women. Subgroup analyses stratified by age were also performed. Results The study enrolled 20,297 participants aged ≥ 19 years (157 RA patients and 20,140 non-RA controls). There was no association between RA and periodontitis or tooth loss in men and women. Subgroup analyses in those aged < 60 years revealed a non-significant association between RA and periodontitis (adjusted odds ratio, 1.53; p = 0.162), but they revealed a significant association between RA and tooth loss (adjusted β, 0.20; p = 0.042). Conclusions RA was not associated with periodontitis, but was associated with tooth loss in younger adults. Younger RA patients are more likely to suffer tooth loss than general younger population; thus dental management is required.

Clinical research is the study of aspects of patient health or illness that are closely related to clinical practice. In the late 20th and early 21th century, outcomes for patients with rheumatoid arthritis (RA) improved dramatically due to breakthroughs in new drugs. Patient-reported outcome measures now play a significant role in the drug development process as study endpoints in clinical trials of new therapies, and this has led to increased interest in the patient's perspective, drug safety and treatment outcomes in clinical practice. In accordance with these needs, many prospective cohorts for RA patients and registries of biologic disease modifying anti-rheumatic drugs have been actively conducted in the United States and European and Asian countries. A gradual shift is taking place in the major outcomes of clinical research using these prospective cohorts and registries. This article will introduce representative registries for RA in each country set up in the early 2000s and will discuss future perspectives in clinical research on RA patients using such clinical registries.

Abstract Background Fluorescence optical imaging (FOI) enables visualization of inflammation in the hands in rheumatic joint diseases with currently a lack of long-term follow-up studies. Objective To investigate FOI for treatment monitoring in a homogenous cohort of patients with early (disease duration 3.2) RA over a period of 12 months. Methods Thirty-five RA patients (24 (68.6%) females, mean age 53.3 years (SD 13.6)) were investigated clinically by DAS28, tender joint count (TJC) and swollen joint count (SJC) and by FOI in phases 1–3 and PrimaVistaMode (PVM) before therapy change and after 12 months. The FOI activity score (FOIAS) was calculated based on individual joint scores from 0 to 3 in 30 joints per patient, adding up to a sum score (0–90). Results We found a statistically significant reduction of FOIAS in phase 1 from baseline (median 5.0, IQR 24.96) to follow-up (median 1.0, IQR 4.0) in all patients (p = 0.0045), both in responders and non-responders according to EULAR response criteria by DAS28. Statistically significant reductions over 12 months were found for median DAS28(ESR) 5.61 to 3.31, TJC 7.0 to 1.0, and SJC 5.0 to 1.0 (each p

Background/Aims To identify the factors associated with time to diagnosis after symptom onset in patients with early rheumatoid arthritis (RA). Methods Early RA patients with ≤ 1 year of disease duration in the KORean Observational study Network for Arthritis (KORONA) database were included in this analysis. Patients were further divided into two groups according to the time to diagnosis from symptom onset: the early diagnosis group (time to diagnosis ≤ 1 year) and the late diagnosis group (time to diagnosis > 1 year). Using the multivariable regression model, we identified factors associated with early diagnosis. Results Among 714 early RA patients, 401 patients (56.2%) and 313 patients (43.8%) were included in the early diagnosis and late diagnosis groups, respectively. The mean disease duration was 0.47 years in the early diagnosis group and 0.45 years in the late diagnosis group. In multivariable model analysis, greater age at onset (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02 to 1.05), high school education or higher (OR, 1.68; 95% CI, 1.14 to 2.47), higher income (OR, 1.48; 95% CI, 1.05 to 2.08), and initial small joint involvement (OR, 1.42; 95% CI, 1.02 to 1.98) were factors associated with early diagnosis. At diagnosis, disease activity scores using 28 joints on diagnosis (3.81 ± 1.44 vs. 3.82 ± 1.42, p = 0.92) and functional disability (0.65 ± 0.61 vs. 0.57 ± 0.62, p = 0.07) did not different between the two groups. However, hand joint erosion on X-ray (37.8% vs. 25.6%, p < 0.01) was more common in the late diagnosis group than the early diagnosis group. Conclusions Older onset age, higher educational level and income, and initial small joint involvement were positive factors for early diagnosis of RA.

Background/Aims To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) Methods The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks. Results Those treated with TCZ showed more favorable outcomes in terms of 20% according to the American College of Rheumatology response criteria (ACR20) and ACR50 responses, individual parameters of ACR core set, disease activity score in 28 joints (DAS28) remission, and European League Against Rheumatism (EULAR) response at week 24. These improvements were maintained or increased during the extension period. DAS28 remission at week 72 was associated with EULAR good response at week 12. The patients who experienced any adverse event (AE) were more frequent in the TCZ group compared to the placebo group. Most AEs were mild or moderate in intensity, although TCZ therapy had possible AEs including serious infection, abnormal liver function, and atherogenic lipid profile. Conclusions TCZ infusion add-on is highly efficacious and well-tolerated in Korean patients with active RA refractory to conventional DMARDs including MTX. EULAR good response at week 12 could predict DAS28 remission at week 72.

Background/Aims Magnetic resonance imaging (MRI) is a sensitive and useful method for the detection of synovitis and joint destruction in rheumatoid arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone marrow edema (BME), synovitis, and tenosynovitis have received insufficient attention. Therefore, this study evaluated the patterns of bone erosion, BME, synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI. Methods MRI datasets from 43 RA patients were analyzed. All patients had undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken, and three had also received MRI of the contralateral wrist and MCP joints. The MR images were evaluated for bone erosion, BME, and synovitis in consensus by two blinded readers according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RAMRIS. The MRI-detected tenosynovitis was evaluated based on Haavardsholm’s tenosynovitis score. Results The capitate, lunate, triquetrum, and hamate bones were the most common sites of erosion and BME and showed the highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was present in 78.3% of all patients with RA, and the extensor compartment 4 and flexor digitorum profundus and superficialis were frequently affected. Conclusions This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice.

ABSTRACT BACKGROUND: Self-efficacy refers to one’s belief in one’s ability to organize, perform actions and face challenges in order to achieve goals and motivation. High self-efficacy improves disease coping and adherence to treatment among patients with rheumatoid arthritis. The objective of this study was to translate, culturally adapt and test the reproducibility of the 8-item Arthritis Self-Efficacy Scale (ASES-8) questionnaire for use in Brazil. DESIGN AND SETTING: Validation study conducted in university outpatient clinics. METHODS: The questionnaire was translated into Brazilian Portuguese and then back-translated into English. The final version in Portuguese was tested on 30 patients with rheumatoid arthritis and was shown to be understandable and culturally adapted. A further 32 patients with rheumatoid arthritis were evaluated three times using the questionnaire. On the first occasion, two evaluators applied the questionnaire to check inter-evaluator reproducibility. After 15 days, one of the evaluators reassessed the patients to verify intra-evaluator reproducibility. At the first assessment, to test the construct validity of ASES-8, the Numerical Pain Scale, Health Assessment Questionnaire, Beck Depression Inventory and Short Form-36 questionnaire were also applied to all the patients. RESULTS: The inter and intra-evaluator correlation coefficients for ASES-8 were high. Cronbach’s alpha was higher than 0.90 for the questionnaire, indicating excellent internal consistency. There were moderate correlations between ASES-8 and most of the instruments tested, indicating good construct validity. CONCLUSION: ASES-8 was translated and adapted to the Portuguese language for Brazil. This instrument is valid, reproducible and reliable for evaluating self-efficacy among patients with rheumatoid arthritis.

Background/Aims To analyze clinical characteristics of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA), especially in patients with poor prognosis. Methods Seventy-seven RA patients with ILD and 231 age, sex, and disease duration-matched RA patients without ILD were enrolled in this retrospective study. Epidemiologic, clinical, and laboratory information were obtained through a medical chart review. Logistic regression analysis was used to estimate the risk of mortality in RA patients with ILD. Results Compared to the RA without ILD group, the RA with ILD group had significantly higher titers of rheumatoid factor and the anti-cyclic citrullinated peptide (p = 0.001 for both), higher levels of C-reactive protein (CRP) at the time of RA diagnosis (p = 0.014), and a higher erythrocyte sedimentation rate (p = 0.022) and CRP levels (p < 0.001) throughout the 10-year follow-up period. These patients also received a higher mean daily dose of corticosteroids (p < 0.001). In the subgroup analysis of RA patients with ILD, 28 patients (36.4%) died during follow-up. Multivariate analysis revealed that older age at the time of ILD diagnosis was significantly associated with mortality. Usual interstitial pneumonia (UIP) subtype on high-resolution computed tomography (HRCT) was also suggested as a poor prognostic factor. Conclusions The survival of RA patients with ILD is adversely affected by age at the time of ILD diagnosis. RA-ILD patients diagnosed after age 65 or with a UIP subtype on HRCT may have a poor prognosis.

The most severe effects of rheumatoid arthritis (RA) are loss of physical function and chronic pain, which may have a major impact on different areas of the person’s existence. The aim of this study was to get an insight into the quality of life (QOL) in subjects with RA in connection with pain perception and functional ability. The following instruments were used: the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF), Short Form Health Survey (SF-36), Health Assessment Questionnaire Disability Index (HAQ-DI) and Visual Analog Scale for Pain (VAS Pain). The results indicated that there was no statistical difference in the QOL between subjects with RA and healthy population according to SF-36 Croatian norms. Also, the results showed that stronger pain experience was significantly associated with poorer social functioning assessment (SF36SF, Spearman’s rho=-0.463, p

Introduction: Still's disease in childhood constitutes an inflammatory disorder, of autoimmune origin, which is framed within the group of juvenile idiopathic arthritis, probably being the most peculiar entity of the group. It usually occurs in the form of repeated outbreaks of activity, combined with periods of remission. Case report: a sixteen-year-old patient with a history of systemic juvenile arthritis is presented, with a clinical picture of 72 hours of evolution characterized by intermittent fever, cough, pyodermitis, generalized rash and arthritis. During the clinical evolution, it was considered base-disease activation versus sepsis supported on clinical criteria, which was later corroborated by laboratory findings. The patient underwent treatment with broad-spectrum antibiotics, non-steroidal anti-inflammatory drugs, steroids at a rate of 1mg / kg / day, without improvement. Subsequently, the treatment with pulses of methylprednisolone and immunomodulator-therapy was initiated. Finally, a macrophage activation syndrome was diagnosed, supported on clinical laboratory parameters. Patient’s evolvement was slowly and died in the Intensive Care Unit, 22 days after the admission. Conclusions: the macrophage activation syndrome is one of the secondary forms within the group of hemophagocytic lymphohistiocytosis. The factors that in this context have been associated with its onset are very diverse. Clinically, these processes are characterized by prolonged fever that does not disappear despite antibiotic-therapy. Typically, arthritis is usually absent. The first line of treatment is corticosteroids at high doses.