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ID PMID Title PublicationDate abstract
30868319 Associations between paraoxonase 1 (PON1) polymorphisms and susceptibility and PON1 activi 2019 Aug OBJECTIVES: We reviewed the associations between paraoxonase 1 (PON1) polymorphisms and susceptibility and PON1 activity in rheumatoid arthritis (RA) patients and compared PON1 activity between RA patients and controls. METHODS: We conducted a meta-analysis of PON1 Q192R and L55M polymorphism and RA risk data and determined the associations between PON1 Q192R polymorphism and PON1 activity in RA patients. We also compared serum/plasma PON1 activity levels in RA patients and controls. RESULTS: Twelve studies were included in this meta-analysis. No association was observed between RA and the PON1 192R allele in any study subject (OR = 0.967, 95% CI = 0.829-1.129, p = 0.674). Analysis using recessive, dominant, or homozygous contrast models revealed no association between the PON1 192R allele and RA. Meta-analysis showed no association between RA and the PON1 55M allele (OR = 1.400, 95% CI = 0.738-2.658, p = 0.308). In the meta-analysis, PON1 activity was significantly higher in the RR genotype than in the QQ (SMD = 2.975, 95% CI = 2.157-3.792, p < 0.001) and QR (SMD = 1.265, 95% CI = 0.898-1.633, p < 0.001) genotypes. PON1 activity was significantly lower in the RA group than in the control group (SMD = - 3.176, 95% CI = - 5.070 to - 1.283, p < 0.001). CONCLUSIONS: We found no association between the PON1 Q192R and L55M polymorphisms and susceptibility to RA, while PON1 Q192R polymorphism was associated with PON1 activity in RA patients; we found significantly lower PON1 activity in RA patients.Key points• PON1 Q192R polymorphism is associated with PON1 activity in RA patients..• PON1 activity is significantly lower in RA patients..
30745806 Temporomandibular Disorders and Oral Features in Early Rheumatoid Arthritis Patients: An O 2019 Aims: Temporomandibular disorders (TMD) represent a heterogeneous group of inflammatory or degenerative diseases of the stomatognatic system, with algic and/or dysfunctional clinical features involving temporomandibular joint (TMJ) and related masticatory muscles. Rheumatoid Arthritis (RA) is an autoimmune polyarthritis characterized by the chronic inflammation of synovial joints and oral implications such as hyposalivation, difficulty in swallowing and phoning, feeling of burning mouth, increased thirst, loss of taste or unpleasant taste and smell, dental sensitivity. The aim of this observational study was to investigate the prevalence of TMD symptoms and signs as well as oral implications in patients with Early Rheumatoid Arthritis (ERA), that is a RA diagnosed within 12 months, compared with a control group. Methods: The study group included 52 ERA patients (11 men, 41 women) diagnosed according to the 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis. A randomly selected group of 52 patients not affected by this disease, matched by sex and age, served as the control group. The examination for TMD signs and symptoms was based on the standardized Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) by means of a questionnaire and through clinical examination. Results: Regarding the oral kinematics, the left lateral excursion of the mandible was restricted in statistically significant way in ERA patients (p=0.017). The endfeel values were significantly increased in ERA group (p=0.0017), thus showing the presence of a higher muscle contracture. On the other side, the study group complained less frequently (67.3%) of TDM symptoms (muscle pain on chewing, pain in the neck and shoulders muscles, difficulty in mouth opening, arthralgia of TMJ, tinnitus) than controls (90.4%) (χ(2)= 8.301 p=0.0039). The presence of TMJ noises was significantly lower in the study group (χ(2)= 3.869 p=0.0049), as well as presence of opening derangement (χ(2)= 14.014 p=0.0002). The salivary flow was significantly decreased in the study group respect to the control one (p<0.0001). Conclusions: The data collected show a weak TMJ kinematic impairment, a paucisymptomatic muscle contracture (positive endfeel) and a remarkable reduction of salivary flow in ERA patients. Myofacial pain (MP) evoked by palpation was more frequent and severe in the control group than in the study one, this result being highly significant.
30210123 An Analysis of the Biological Disease-modifying Antirheumatic Drug-free Condition of Adali 2019 Feb 15 Objectives The present study was performed with the aim of analyzing the biological disease-modifying antirheumatic drug (bDMARD)-free (Bio-free) condition of adalimumab (ADA)-treated rheumatoid arthritis (RA) patients in a real-world setting. Methods ADA was used in the treatment of 130 (male, n=21; female, n=109 females) RA patients. Among them, 26 patients (20.0%) discontinued ADA due to a good response. We analyzed 20 patients who were followed up for more than 6 months after the discontinuation of ADA. The Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) and modified health assessment questionnaires (mHAQs) were evaluated. Results The mean age of the patients was 53.4±11.1 years. The mean disease duration was 4.5±4.3 years. Sixteen patients were bDMARD-naïve, while 4 switched from bDMARDs to ADA. At 6 months after the discontinuation ADA, 19 patients had achieved a clinical remission, and 1 had achieved a low disease activity. The Bio-free period was 26.4±15.5 months. The dose of prednisolone was significantly reduced from baseline (3.45±3.17 mg/day) at 6 months after the discontinuation of ADA (2.63±2.78 mg/day). The dose of methotrexate was unchanged. The number of conventional synthetic DMARDs (csDMARDs) was significantly increased (0.8±0.6 to 1.4±1.06). The mHAQ values were significantly ameliorated by ADA and remained good in patients with a Bio-free condition. A multivariate analysis showed that the dose of methotrexate (MTX) was an important factor for achieving a Bio-free condition. Conclusion A sustainable Bio-free condition in a real clinical setting can be achieved and may be a suitable way of reducing medical costs. The dose of MTX and the additional administration of csDMARDs is therefore thought to be important for ensuring a good outcome in these patients.
30242542 miR-410-3p Suppresses Cytokine Release from Fibroblast-Like Synoviocytes by Regulating NF- 2019 Feb miR-410-3p acts as an oncogene or a tumor suppressor in some malignancies. However, its role in rheumatoid arthritis (RA) is unknown. The study was conducted to investigate the effect of miR-410-3p on the pathogenesis of RA. Real-time RT-PCR was used to determine the mRNA levels of miR-410-3p in synovial tissues and fibroblast-like synoviocytes (FLSs). An ELISA was performed to examine the production levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and matrix metalloproteinase (MMP)-9. Western blotting was conducted to determine the protein levels of IκB-α, p-IκBα, p65, and p-p65. Nuclear factor (NF)-κB activation and nuclear translocation assays were performed to confirm the activation of NF-κB. We found that the expression level of miR-410-3p was downregulated in synovial tissues and FLSs from RA. Overexpression of miR-410-3p significantly reduced the secretion of TNF-α, IL-1β, IL-6, and MMP-9 in human RA fibroblast-like synoviocytes (HFLS-RA); whereas miR-410-3p inhibition increased the expression levels of these cytokines. Furthermore, miR-410-3p suppresses the activation of NF-κB signaling pathway. Moreover, NF-κB inhibitor restored the elevation of TNF-α, IL-1β, IL-6, and MMP-9 induced by miR-410-3p inhibition. Our results demonstrate that miR-410-3p acts an inflammatory suppressor in the pathogenesis of RA by regulating the NF-κB signaling pathway. These data suggest a novel function of miR-410-3p and provide insight into the complex mechanisms involved in RA.
31342161 Reality of care for musculoskeletal diseases at the population level : Results of the PROC 2019 Dec BACKGROUND: The objective of the research consortium PROCLAIR was to gain population level knowledge on the treatment of patients with rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and osteoarthritis (OA) in Germany. AIMS: A main question of the consortium was whether it is possible to identify groups of people who were exposed to a particular risk of undersupply or oversupply of treatment. In addition, the study investigated the validity of claims data for these diseases as a basis for further studies. PATIENTS AND METHODS: Cross-sectional surveys were carried out among insurees of the BARMER statutory health insurance fund whose claims data included RA, axSpA and OA diagnoses. The questionnaire data were linked with the claims data of the insured persons if they agreed. RESULTS: In all three diseases risk groups for care deficits could be identified. Persons with RA who are not treated by a specialist have less access to drug treatment. Physical therapy is prescribed for all three diagnoses at a low level, even for people undergoing joint replacement surgery. A connection between depressive symptoms and disease activity or function in axSpA was shown. In addition to the results relevant to care, the PROCLAIR network has also made contributions to critically assess the quality of health insurance data. DISCUSSION: The combination of billing data with survey data enables a comprehensive description of the treatment of musculoskeletal diseases. Particularly relevant factors are the specialization of the physician, sociodemographic parameters of the patients and the region of residence. In particular, access to treatment cannot be investigated in randomized clinical trials.
30729557 Network meta-analysis of tofacitinib versus biologic treatments in moderate-to-severe rheu 2019 Jun WHAT IS KNOWN AND OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by inflammation and pain in the joints. Tofacitinib is an oral drug recently approved for RA treatment; it inhibits Janus protein kinases (JAK) that reduces RA symptoms when conventional DMARDs do not trigger a response. This study aimed to compare the efficacy of biological DMARDs in monotherapy or combined with methotrexate in RA patients and compare the treatments. METHODS: We reviewed the literature for articles published up to June 2017, evaluating the efficacy and safety of the biological DMARDs indicated for RA in patients with inadequate responses to conventional DMARDs and naïve to biological DMARDs, in similar populations, considering ACR50 as the efficacy variable. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each drug combination, and these parameters were transformed into differences in responses to assess the effectiveness of the alternative medicines. Equivalence therapeutic alternatives (ETA) were ensured to assess the possibility of considering these medications with equivalent efficacy. A network meta-analysis (NMA) was performed using Bayesian approaches and the fixed-effects model. RESULTS AND DISCUSSION: Twenty-seven randomized clinical trials (RCTs) that met the pre-established criteria were identified. The 95% CI of biological DMARDs was higher than that of placebo without methotrexate, except for certolizumab, golimumab-m, anakinra-m and adalimumab monotherapy. These DMARDs performed significantly better than the placebo, except for etanercept, certolizumab, tofacitinib and golimumab. Certolizumab-m was better than anakinra-m and adalimumab, and tocilizumab alone or combined with methotrexate was superior to adalimumab. Etanercept-m yielded a higher difference in responses compared with the other biological DMARDs, which presented more homogeneous responses, except for adalimumab and anakinra-m, which yielded worse results. None of the biological DMARDs displayed ETA to etanercept-m; however, they displayed ETA with certolizumab-m, except for adalimumab and anakinra-m. WHAT IS NEW AND CONCLUSION: All biological DMARDs used in combination with methotrexate, except for etanercept, anakinra, certolizumab and tocilizumab without methotrexate, were displayed ETA on using ACR50 at week 24 in patients naïve to biological DMARDs. Etanercept displayed a greater difference in responses, although the high uncertainty of the comparative results prevented the confirmation of the increased efficacy of this drug.
30597393 Rheumatoid meningitis sine arthritis. 2019 Mar 15 Rheumatoid meningitis is a rare and very serious extra-articular manifestation of rheumatoid arthritis. We present a case of a 7()year-old female with no history of arthritis who developed stroke-like symptoms, seizures, psychosis and compulsive behavior. Serial brain magnetic resonance images (MRI) over four months demonstrated progressive interhemispheric meningeal thickening. She had mild lymphocytic pleocytosis on the cerebrospinal fluid analysis and serum anti-cyclic citrullinated peptide antibodies resulted positive in high titers. She underwent a brain biopsy showing necrotizing granulomas consistent with rheumatoid meningitis. Her symptoms resolved with treatment with glucocorticoids and cyclophosphamide. She has not been diagnosed with rheumatoid arthritis even after 1 year of follow up. Clinicians should be aware of the possibility of rheumatoid meningitis without rheumatoid arthritis and keep it on the differential for patients with aseptic meningitis and otherwise negative work up.
30508189 Assessments of the unmet need in the management of patients with rheumatoid arthritis: ana 2019 Mar 1 OBJECTIVE: To describe the outcomes of MTX and biologic DMARD (bDMARD) treatment in patients with RA and assess unmet needs in patients who fail treatment, using real-world data from the Norwegian DMARD (NOR-DMARD) registry. METHODS: Data included RA treatment courses from January 2007 until July 2016. Patients received MTX monotherapy (in MTX-naïve patients), bDMARD monotherapy, bDMARDs + MTX, or bDMARDs + other conventional synthetic DMARDs (csDMARDs). DAS28-4(ESR) was used to measure remission (<2.6) and inadequate response (>3.2) across all groups at Months 6 and 12. Estimated ACR20/50/70 and EULAR good and good/moderate response rates (based on DAS28-4[ESR] score) for bDMARDs were modelled at Months 6 and 12 using logistic mixed regression. DAS28-4(ESR) scores and changes from baseline, and rates and reasons for discontinuation, were evaluated for all groups over 24 months. RESULTS: The 2778 treatment courses in this analysis included 714 MTX monotherapy, 396 bDMARD monotherapy, 1460 bDMARDs + MTX and 208 bDMARDs + other csDMARDs. Of patients with DAS28-4(ESR) data at Months 6 and 12 (25.0-34.1%), 33.9-47.2% did not switch treatment and were inadequate-responders at Month 12. There were no significant differences in efficacy between bDMARD groups (bDMARD monotherapy, or bDMARDs + MTX or other csDMARDs). Lack of efficacy was the most common reason for stopping treatment across all groups (13.7-22.1% over 24 months). CONCLUSION: An unmet treatment need exists for patients still experiencing inadequate response to MTX monotherapy and bDMARDs as monotherapy or in combination with MTX/other csDMARDs after 12 months. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01581294.
31918275 Molecular mechanisms and clinical application of Iguratimod: A review. 2020 Feb Iguratimod (IGU) is a novel small-molecule anti-rheumatic drug with remarkable effectiveness and good safety for the treatment of active rheumatoid arthritis. Its mechanism of action is related to its ability to act simultaneously on T and B lymphocytes. IGU can effectively inhibit expression of various inflammatory factors, inhibit B cells from producing immunoglobulins and autoantibodies, downregulate T-cell-mediated cellular immunity, accelerate bone formation, and exert some activity against anti-pulmonary fibrosis. In recent years, IGU has been gradually applied to the treatment of a variety of rheumatic diseases, such as Sjögren's syndrome, ankylosing spondylitis and systemic lupus erythematosus. This article reviews the mechanism of action and clinical research status of IGU, and provides reference for future research on its mechanism of action and clinical application.
28676287 Analysis of effectiveness, safety and optimization of tocilizumab in a cohort of patients 2019 Jan OBJECTIVE: To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. MATERIAL AND METHODS: Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan-Meier. RESULTS: The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6-86.7]). Twenty-one of 53 patients (39.6%) optimized the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. CONCLUSIONS: Tocilizumab appears to be effective and safe in RA in clinical practice. The optimized regimen appears to be effective in most patients in remission, even when they change from IV to SC.
31004305 Oral health-related quality of life among individuals with rheumatoid arthritis. 2019 Sep OBJECTIVE: To evaluate the oral health-related quality of life (OHRQoL) of individuals with rheumatoid arthritis (RA) in comparison with individuals with no RA. METHOD: A cross-sectional study was carried out with 112 individuals distributed into two groups. Group 1 (G1) consisted of 42 RA individuals and group 2 (G2) consisted of 70 individuals without RA. Participants' OHRQoL was assessed by means of the long form of the Oral Health Impact Profile (OHIP). The OHIP has 49 questions distributed across seven domains: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap. The overall score ranges between 0 and 196. A higher score denotes a greater negative impact on OHRQoL. All participants underwent oral examination for the evaluation of clinical variables. Sociodemographic and oral behavior variables were also collected. Data analysis included descriptive statistics, Mann-Whitney test, and regression analysis. RESULTS: Individuals in G1 presented higher OHIP overall score (p = 0.006) than G2 individuals. G1 individuals also presented higher scores in the functional limitation (p = 0.003) and the physical disability (p = 0.005) domains than G2 individuals. Individuals with RA (p = 0.044), individuals who brushed their teeth less often (p = 0.019), and those with a higher number of decayed, missing, and filled teeth (DMFT) (p = 0.038) presented a significantly higher OHIP-49 overall score (more negative perception of their OHRQoL) than individuals without RA, individuals who brushed their teeth more often, and those with a lower DMFT. CONCLUSION: RA individuals had a more negative perception of their OHRQoL compared with individuals with no RA.
31481105 Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, 2019 Sep 3 BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of morbidity and mortality, when compared with general population, largely due to enhanced atherosclerotic disease. In this work, we aimed at assessing both occurrence and predictive factors of subclinical and clinical atherosclerosis in RA. METHODS: From January 1, 2015, to December 31, 2015, consecutive participants with RA, admitted to Italian Rheumatology Units, were assessed in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort. After that, those participants were followed up in a 3-year, prospective, observational study, assessing the occurrence of subclinical and clinical atherosclerosis and possible predictive factors. McNemar test was employed to assess the changes in subclinical and clinical atherosclerosis, and regression analyses exploited the ORs for the occurrence of those comorbidities. RESULTS: We analysed 841 participants, mostly female (82.2%) and with median age of 60 years (range 21-90). The remission was achieved and maintained by 41.8% of participants during the follow-up. We observed an increased rate of subclinical atherosclerosis at the end of follow-up (139 vs 203 participants, p < 0.0001), particularly in participants with a disease duration less than 5 years at baseline (70 participants vs 133 participants, p < 0.0001). Type 2 diabetes (T2D) (OR 4.50, 95%CI 1.74-11.62, p = 0.002), high blood pressure (OR 2.03, 95%CI 1.04-4.14, p = 0.042), ACPA (OR 2.36, 95%CI 1.19-4.69, p = 0.014) and mean values of CRP during the follow-up (OR 1.07, 95%CI 1.03-1.14, p = 0.040) were significantly associated with higher risk of subclinical atherosclerosis. We observed an increased rate of clinical atherosclerosis at the end of follow-up (48 vs 76 participants, p < 0.0001). T2D (OR 6.21, 95%CI 2.19-17.71, p = 0.001) was associated with a significant risk of clinical atherosclerosis. The achievement and the maintenance of remission reduced the risk of subclinical (OR 0.25, 95%CI 0.11-0.56, p = 0.001) and clinical atherosclerosis (OR 0.20, 95%CI 0.09-0.95, p = 0.041). CONCLUSIONS: We reported an increased prevalence and incidence of both subclinical and clinical atherosclerosis in 3-year prospectively followed participants, mainly in the subset with a duration of disease less than 5 years. The achievement and the maintenance of remission are associated with a reduction of the risk of subclinical and clinical atherosclerosis. Among "traditional" cardiovascular risk factors, participants with T2D showed a higher risk of clinical and subclinical atherosclerosis.
30876479 RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclas 2019 Mar 15 BACKGROUND: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease characterized by upregulation of inflammatory cell death and osteoclastogenesis. Necrostatin (NST)-1s is a chemical inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK)1, which plays a role in necroptosis. METHODS: We investigated whether NST-1s decreases inflammatory cell death and inflammatory responses in a mouse model of collagen-induced arthritis (CIA). RESULTS: NST-1s decreased the progression of CIA and the synovial expression of proinflammatory cytokines. Moreover, NST-1s treatment decreased the expression of necroptosis mediators such as RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL). In addition, NST-1s decreased osteoclastogenesis in vitro and in vivo. NST-1s downregulated T helper (Th)1 and Th17 cell expression, but promoted Th2 and regulatory T (Treg) cell expression in CIA mice. CONCLUSIONS: These results suggest that NST-1s attenuates CIA progression via the inhibition of osteoclastogenesis and might be a potential therapeutic agent for RA therapy.
31612758 Feasibility of patient-oriented ultrasound joint selection: Cross-sectional observational 2020 Nov Objective: Ultrasonography (US) is a useful tool for evaluating the activity of rheumatoid arthritis (RA) patients. As the systemic evaluation of many joints is time-consuming, a method to evaluate this activity with a smaller number of joints is needed. The aim of this study was to clarify whether the number of joints assessed may be reduced using patient-oriented joint selection.Methods: A total of 492 RA patients were recruited at Kyoto University Hospital. Bilateral metacarpophalangeal (MCP), (proximal) interphalangeal (PIP/IP), and wrist joints were evaluated by US. Gray scale and power Doppler imaging findings were scored by a 0-3 semi-quantitative method. Clinical assessments were performed by physicians who were blind to US results, and a questionnaire on subjective symptoms was collected from each patient.Results: The correlation between the US score of all 22 joints (US22) and patient-oriented painful joints (PtUS) or physician-oriented tender and/or swollen joints were moderate (Spearman's ρ = 0.435) and weak (ρ = 0.383), respectively. These correlations were weaker than that between the total US score of 5 preselected joints (unilateral 2MCP, 3MCP, 2PIP, 3PIP, and the wrist) and US22 (ρ = 0.813). However, when focusing on patients whose painful joints were 5 and more, the correlation between PtUS and US22 was markedly stronger (ρ = 0.757).Conclusion: Patient-oriented joint selection reflected actual joint inflammation to some extent. However, excessive reductions in the number of joints assessed need to be avoided even if patients do not have arthralgia because of the potential for underestimations.
30997153 Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179 2019 OBJECTIVE: To investigate the efficacy, safety and immunogenicity of PF-06438179/GP1111 (PF-SZ-IFX) compared with European reference infliximab (Remicade(®); ref-IFX) in patients with moderate-to-severe, active rheumatoid arthritis after continued long-term use of PF-SZ-IFX, and in patients who were switched from ref-IFX to PF-SZ-IFX. METHODS: REFLECTIONS B537-02 was a double-blind, active-controlled, multinational study in which patients (N=650) were initially randomised to PF-SZ-IFX or ref-IFX for 30 weeks (treatment period [TP] 1). During weeks 30-54 (TP2), the PF-SZ-IFX group (n=280) continued treatment with PF-SZ-IFX (PF-SZ-IFX/PF-SZ-IFX) and patients in the ref-IFX group (n=286) were rerandomised (1:1) to continue ref-IFX (ref-IFX/ref-IFX) (n=143) or switch to PF-SZ-IFX (ref-IFX/PF-SZ-IFX) (n=143) for a further 24 weeks. Efficacy, safety, immunogenicity and pharmacokinetics were evaluated. RESULTS: During TP2, patients in all three treatment groups continued to maintain comparable treatment response. At week 54, the American College of Rheumatology (ACR20) response rates were 71.1% (PF-SZ-IFX/PF-SZ-IFX), 64.3% (ref-IFX/ref-IFX) and 70.6% (ref-IFX/PF-SZ-IFX). Observations for other endpoints, including ACR50/70, Disease Activity Score in 28 Joints Based on High-Sensitivity C Reactive Protein(DAS28-CRP) remission, and mean change in DAS28-CRP and Health Assessment Questionnaire-Disability Index, were also comparable. Treatment-emergent adverse events were reported in 36.8% (PF-SZ-IFX/PF-SZ-IFX), 33.6% (ref-IFX/ref-IFX) and 37.8% (ref-IFX/PF-SZ-IFX) of patients; there were no clinically meaningful differences in the safety profiles between groups. The percentage of patients who were antidrug antibody-positive was generally stable through the treatment period and comparable overall between the PF-SZ-IFX/PF-SZ-IFX (52.1%; neutralising: 80.8%), ref-IFX/ref-IFX (60.1%; neutralising: 84.9%) and ref-IFX/PF-SZ-IFX (58.0%; neutralising 78.3%) groups. CONCLUSIONS: The similar efficacy, safety and immunogenicity of PF-SZ-IFX compared with ref-IFX were maintained for up to 54 weeks and were not affected by blinded treatment switch from ref-IFX to PF-SZ-IFX at week 30. TRIAL REGISTRATION NUMBER: NCT02222493.
31371305 Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activ 2019 Nov OBJECTIVE: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly targets joints. Monocytes and macrophages are critical in RA pathogenesis and contribute to inflammatory lesions. These extremely plastic cells respond to extracellular signals which cause epigenomic changes that define their pathogenic phenotype. Here, we interrogated how DNA methylation alterations in RA monocytes are determined by extracellular signals. METHODS: High-throughput DNA methylation analyses of patients with RA and controls and in vitro cytokine stimulation were used to investigate the underlying mechanisms behind DNA methylation alterations in RA as well as their relationship with clinical parameters, including RA disease activity. RESULTS: The DNA methylomes of peripheral blood monocytes displayed significant changes and increased variability in patients with RA with respect to healthy controls. Changes in the monocyte methylome correlate with DAS28, in which high-activity patients are divergent from healthy controls in contrast to remission patients whose methylome is virtually identical to healthy controls. Indeed, the notion of a changing monocyte methylome is supported after comparing the profiles of same individuals at different stages of activity. We show how these changes are mediated by an increase in disease activity-associated cytokines, such as tumour necrosis factor alpha and interferons, as they recapitulate the DNA methylation changes observed in patients in vitro. CONCLUSION: We demonstrate a direct link between RA disease activity and the monocyte methylome through the action of inflammation-associated cytokines. Finally, we have obtained a DNA methylation-based mathematical formula that predicts inflammation-mediated disease activity for RA and other chronic immune-mediated inflammatory diseases.
31037458 Evaluation of factors affecting the levels of physical activity in patients with rheumatoi 2019 Sep Relatively little is known about what motivates or prevents patients with rheumatoid arthritis (RA) from adopting physically active lifestyles. This study aimed to evaluate the levels of physical activity and to identify the factors affecting a physically active lifestyle among Korean patients with RA. In this cross-sectional study, data were collected from a rheumatology outpatient clinic of a university-affiliated hospital in South Korea. The levels of physical activity were self-reported using the International Physical Activity Questionnaire. Participants who engaged in more than 600 metabolic equivalent task-minutes/week of physical activity and moderate activity or walking at least three times per week were considered physically active in this study. Structured questionnaires were used to assess perceived barriers and self-efficacy for exercise. Of 345 patients with RA included in this study, about 22% of patients were classified as physically active. Factors associated with a physically active lifestyle were good physical function (odds ratio [OR] = 0.56; 95% confidence interval [CI]: 0.36-0.87) and high levels of exercise self-efficacy (OR = 1.36; 95% CI: 1.20-1.54). Common barriers identified were fatigue, interference with other responsibilities, and a lack of time. Participants showed the lowest self-efficacy for exercise when they had pain and were busy with other activities. The level of physical function and exercise self-efficacy were predictors of physical activity. Individualized physical activity programs tailored to personal abilities and barriers and increasing exercise self-efficacy are needed to facilitate engagement of physical activity in Korean patients with RA. KEY POINTS: • Factors associated with a physically active lifestyle were good physical function and high levels of exercise self-efficacy. • The levels of exercise self-efficacy in Korean patients with RA are low compared to those in other populations. • Frequently encountered barriers in the subjects were being too tired, interference with other responsibilities, and lack of time. • Individualized physical activity programs tailored to personal abilities and barriers and increasing exercise self-efficacy are needed to facilitate engagement of physical activity in Korean patients with RA.
30506552 Longitudinal Occurrence and Predictors of Patient-Provider Discordance Between Global Asse 2020 Jan OBJECTIVE: To identify longitudinal predictors of discordance between patients with rheumatoid arthritis (RA) and their health care providers, where patient global assessment of disease activity is substantially higher than provider global assessment. METHODS: This retrospective case-control study included 102 cases with positive discordance (i.e., ≥25 mm between patient and provider global assessments) and 102 controls without discordance who were matched for age, sex, RA duration, and Clinical Disease Activity Index (CDAI) score. Data were collected at the baseline visit (date of diagnosis or earliest available visit), the index visit (participation in a previous cross-sectional study), and at up to 11 additional visits before the index visit. Data included patient characteristics, disease activity measures, Disease Activity Score in 28 joints (3-variable) using the C-reactive protein level (DAS28-CRP), and medications. Data were analyzed by using linear and logistic regression models with smoothing splines for nonlinear trends. RESULTS: Overall, the mean age was 63 years, 75% of patients were female, and the mean RA duration was 10 years. Compared with controls, cases had higher rates of discordant visits during the 4 years before the index visit, and they had a higher CDAI score and DAS28-CRP earlier in the disease course. Cases more frequently had antinuclear antibodies, nonerosive disease, prior depression, or prior use of antidepressants or fibromyalgia medications. Disease-modifying medication use was not different between cases and controls. CONCLUSION: The findings inform new hypotheses about the relationships of disease activity and antinuclear antibodies to the later occurrence of positive discordance among patients with RA.
30345719 Back to the basics: Understanding joint swelling and tenderness at the wrist in rheumatoid 2019 Jan AIM: To compare ultrasound-detected inflammation with clinical manifestations at the wrist in rheumatoid arthritis (RA). METHOD: Wrists assessed serially by assessors blinded to ultrasound findings were categorized into 4 groups: 1 = S0T0 (not swollen; not tender); 2 = S0T1 (not swollen; tender); 3 = S1T0 (swollen; not tender); 4 = S1T1 (swollen; tender). Ultrasound synovitis and tenosynovitis were graded semi-quantitatively (0-3) and dichotomously (0 or 1), respectively. The (a) power Doppler (PD), gray-scale (GS) and combined (PD + GS) ultrasound (CUS) scores and (b) their positivity (score > 0) were analyzed using a general linear repeated measures mixed model (a) assuming Gaussian errors and (b) with binary distribution and logit link, respectively. Pairwise comparisons among wrist groups were performed within context of the models. RESULTS: In 122 wrist assessments (baseline = 64; 3 months = 58) from 32 treated RA patients (87.5% female; mean disease duration 42.8 months), significant differences among groups for (a) scores were: 4 vs 1 (PD, P = 0.0031; GS, P = 0.0159; CUS, P = 0.0045), 4 vs 2 (PD, P = 0.0176; GS, P = 0.0160; CUS, P = 0.0074), and 4 vs 3 (CUS, P = 0.0374); and (b) positivity were: 4 vs 1 (PD, P = 0.0007), 4 vs 2 (PD, P = 0.0234), and 3 vs 1 (PD, P = 0.0202). No significant differences in results were found for groups 2 vs 1. No significant effects were attributable to differences in wrist side or follow-up visit. CONCLUSION: Ultrasound detected substantial inflammation when wrist joint swelling and tenderness are both present. Joint swelling without tenderness is associated with significantly more frequent PD detection. Without swelling, joint tenderness is not associated with a significantly greater degree of ultrasound-detected inflammation.
31145347 Ultrasound-guided lumbar selective nerve root block plus T12 paravertebral and sacral plex 2019 May RATIONALE: For hip or knee arthroplasty, it is essential to develop a satisfied peripheral nerve block method that will benefit elderly patients or patients who are contraindicated to neuraxial anesthesia. PATIENTS CONCERNS: Patient in Case 1 suffered from the right intertrochanteric fracture, combined with chronic obstructive pulmonary disease; Patient in Case 2 suffered from hip osteoarthritis; combined with ankylosing spondylitis; Patient in Case 3 suffered from rheumatoid arthritis, combined with ischemic encephalopathy. DIAGNOSIS: Case 1: Right intertrochanteric fracture, chronic obstructive pulmonary disease. Case 2: hip osteoarthritis. Case 3: rheumatoid arthritis. INTERVENTIONS: Ultrasound-guided lumbar selective nerve root block (SNRB) plus T12 paravertebral and sacral plexus block were performed in 2 patients who received hip arthroplasty and 1 patient who received knee arthroplasty. OUTCOMES: All patients successfully received surgeries with this peripheral nerve block method and no postoperative complication was reported. LESSONS: Ultrasound-guided lumbar SNRB plus T12 paravertebral and sacral plexus block not only satisfied the analgesia requirement of surgery, but also reduced the consumption of local anesthetic.