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ID PMID Title PublicationDate abstract
31435754 Efficacy and retention rate of adalimumab in rheumatoid arthritis and psoriatic arthritis 2020 Feb Few studies have compared the efficacy of switching from etanercept to adalimumab in the real-life setting in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This study evaluated the 2-year retention rate and 12-month efficacy of adalimumab in RA and PsA patients, previously treated with etanercept. RA and PsA patients from 11 Italian Rheumatology Units received adalimumab after first-line etanercept failure. Two-year adalimumab retention rate was calculated by the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of drug persistence. Univariate and multivariate logistic regression analyses were developed to examine potential predictors of 12-month DAS-28 remission. The study population included 117 RA (disease duration of 10.1 ± 7.7 years and baseline DAS28-ESR of 4.97 ± 1.3) and 102 PsA (disease duration of 7.1 ± 5.1 years and baseline DAPSA of 24.6 ± 11.8). The 2-year retention rate was 48.2% in RA and 56.5% in PsA patients. Concomitant methotrexate treatment was not associated with increased drug survival in both groups. Similarly, cause of etanercept discontinuation or treatment duration was not associated with retention rate. 12-month remission and low disease activity were achieved, respectively, in 27.3% and 23.9% of RA patients and 27.4% and 23.5% PsA of patients. In multivariate models, etanercept discontinuation due to inefficacy (OR 0.27, 95% CI 1.03-0.73; p = 0.009) and baseline DAS-28 (OR 0.45, 95% CI 0.29-0.69; p < 0.001) remained significant negative predictors of remission in RA patients. No variable was associated with remission in PsA patients. Adalimumab after etanercept failure was highly effective and safe in both RA and PsA patients.
31342120 CCL21/CCR7 signaling in macrophages promotes joint inflammation and Th17-mediated osteocla 2020 Apr In rheumatoid arthritis (RA), synovial tissue abundantly expresses CCL21, a chemokine strongly associated with RA susceptibility. In this study, we aimed to characterize the functional significance of CCL21/CCR7 signaling in different phases of RA pathogenesis. We determined that CCR7 is a hallmark of RA M1 synovial fluid (SF) macrophages, and its expression in RA monocytes and in vitro differentiated macrophages is closely associated with disease activity score (DAS28). In early stages of RA, monocytes infiltrate the synovial tissue. However, blockade of SF CCL21 or CCR7 prevents RA SF-mediated monocyte migration. CCR7 expression in the newly migrated macrophages can be accentuated by LPS and IFNγ and suppressed by IL-4 treatment. We also uncovered that CCL21 stimulation increases the number of M1-polarized macrophages (CD14+CD86+), resulting in elevated transcription of IL-6 and IL-23. These CCL21-induced M1 cytokines differentiate naïve T cells to Th17 cells, without affecting Th1 cell polarization. In the erosive stages of disease, CCL21 potentiates RA osteoclastogenesis through M1-driven Th17 polarization. Disruption of this intricate crosstalk, by blocking IL-6, IL-23, or IL-17 function, impairs the osteoclastogenic capacity of CCL21. Consistent with our in vitro findings, we establish that arthritis mediated by CCL21 expands the joint inflammation to bone erosion by connecting the differentiation of M1 macrophages with Th17 cells. Disease progression is further exacerbated by CCL21-induced neovascularization. We conclude that CCL21 is an attractive novel target for RA therapy, as blockade of its function may abrogate erosive arthritis modulated by M1 macrophages and Th17 cell crosstalk.
30856693 [Expression of matrix metalloproteinase-3 in patients with reheumatoid arthritis and its c 2019 Mar 9 Objective: To detect the expression of matrix metalloproteinase-3 (MMP-3) in serum and gingival crevicular fluid in patients with rheumatoid arthritis (RA) and its correlation with chronic periodontitis (CP). Methods: From March 2017 to July 2018, 26 patients with RA and CP [CP+RA group, (54.9±6.5) years old, 4 males and 22 females], 22 patients with RA only [RA group, (49.6±11.7) years old,5 males and 17 females] in the Department of Rheumatology and Immunology, Shengjing Hospital Affiliated to China Medical University, 22 patients with simple CP in the Department of Stomatology, Shengjing Hospital Affiliated to China Medical University [CP group, (51.4±12.5) years old, 8 males and 14 females] and 18 generally healthy controls in Physical Examination Center of Shengjing Hospital Affiliated to China Medical University [group H, (49.4±9.1) years old, 8 males and 10 females] were recruited. There were no significant differences in age and sex ratio amongst 4 groups. Patient's general status, probing depth (PD) , clinical attachment loss (CAL), sulcus bleeding index (SBI), simplified calculus index (CI-S) and simplified debris index (DI-S) were recorded in 4 groups. Samples of serum and gingival crevicular fluid were collected from patients of each group, and the expression levels of MMP-3 in serum and gingival crevicular fluid samples were detected by using enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate, rheumatoid factor, anti-cyclic citrulline peptide antibody and C-reactive protein were detected in the serum of subjects in RA group and CP+RA group. Correlation analysis was conducted between MMP-3 expression level and periodontal indices amongst 4 groups. The results were statistically analyzed using the SPSS 20.0 software package. Results: The indices of CAL [(4.12±1.13) mm], SBI (2.58±0.64) and DI-S (2.65±0.69) in CP+RA group were significantly higher than indices of CAL [(3.00±0.00) mm], SBI (2.59±1.05) and DI-S, (2.36±0.49) in CP group (P<0.05); The expression levels of MMP-3 in serum samples of CP+RA group [(1 1645.6±6 903.4) μg/L] and CP group [(9 337.0±6 719.0) μg/L] were significantly higher than that of RA group [(2 389.9±1 320.3) μg/L] and H group [(1 493.5±292.1) μg/L] (P<0.05). The expression level of MMP-3 in gingival crevicular fluid samples of CP+RA group [(164.4±45.3) μg/L] was significantly higher than that of CP group [(84.6±92.5) μg/L], RA group [(49.0±18.1) μg/L] and H group [(20.4±6.3) μg/L] (P<0.05), respectively. The erythrocyte sedimentation rate, rheumatoid factor and anti-cyclic cirullinated peptide antibodies levels in the CP+RA group were significantly higher than those in the RA group (P<0.05). The expression level of MMP-3 in serum is positively correlated with PD (r=0.45, P=0.04) and the expression level of MMP-3 in gingival crevicular fluid is positively correlated with CAL (r=0.58, P<0.01). Conclusions: The levels of MMP-3 in serum and gingival crevicular fluid of patients with RA and CP were significantly increased. MMP-3 may be associated with the development of CP and RA.
30668267 Expression Profile of Long Noncoding RNAs, lnc-Cox2, and HOTAIR in Rheumatoid Arthritis Pa 2019 Mar Despite the increased proof that long noncoding RNAs (lncRNAs) can control gene expression and broadly affect the normal physiological and disease conditions, the part of lncRNAs in rheumatoid arthritis (RA) is not well known. This study aimed to assess the serum expression levels of lnc-Cox2 and HOTAIR in RA and to investigate their role as novel noninvasive biomarkers in diagnosis of RA. Also, their relations with the levels of interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 and with other clinicolaboratory data in RA patients were analyzed. LncRNAs-Cox2 and HOTAIR expression levels were detected in serum by real-time quantitative polymerase chain reaction. Both IL-6 and MMP-9 levels in serum were measured by enzyme-linked immunosorbent assay. The mRNA expression of lncRNA-Cox2 and HOTAIR was significantly upregulated in RA patients compared with healthy controls. Serum levels of both IL-6 and MMP-9 were significantly higher in RA patients than in healthy subjects (P < 0.001 each). Receiver operating characteristic (ROC) curve demonstrated that lncRNA-Cox2 and HOTAIR could discriminate RA patients from healthy controls. HOTAIR (not lnc-Cox2) was observed to be an independent predictor for RA using multiple logistic regression analysis. We concluded that lnc-Cox2 and HOTAIR serum expression levels can be used as novel noninvasive biomarkers for the diagnosis of RA.
31327319 Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in 2019 Jul 22 OBJECTIVES: Since low insulin-like growth factor (IGF) 1 is often linked to inflammation, we analyze whether serum levels of IGF1 are associated with cardiovascular disease (CVD) in rheumatoid arthritis (RA) in a longitudinal observational study. METHODS: A CVD risk was estimated (eCVR) in 184 female RA patients (mean age 52 years) and in 132 female patients after ischemic stroke (mean age 56 years) with no rheumatic disease, using the Framingham algorithm. The median level of IGF1 divided the cohorts in IGF1(high) and IGF1(low) groups. A 5-year prospective follow-up for new CVD events was completed in all RA patients. The Mantel-Cox analysis and event-free survival curves were prepared. Unsupervised clustering of proteins within the IGF1 signaling pathway was employed to identify their association with eCVR. RESULTS: Low IGF1 resulted in a higher eCVR in RA patients (7.2% and 3.3%, p = 0.0063) and in stroke (9.3% and 7.1%, p = 0.033). RA had higher rate for new CVD events at prospective follow-up (OR 4.96, p = 0.028). Hypertension was the major risk factor associated with low IGF1 in RA and stroke. In hypertension, IGF1 was no longer responsible for intracellular activation and lost its correlation to IRS1/2 adaptor proteins. The clustering analysis confirmed that combination of low IGF1 and IRS1/2 with high IL6, insulin, and glucose predisposed to high eCVR and emphasized the functional role of serum IGF1. CONCLUSIONS: Low serum IGF1 precedes and predicts development of early CVD events in female RA patients. Hypertension and aberrant IGF1 receptor signaling are highlighted as the important contributors to IGF1-related CVD events.
31857525 An Institutional Review of Tuberculosis Spine Mimics on MR Imaging: Cases of Mistaken Iden 2019 Nov Although MRI has a spectrum of findings which help in the diagnosis of tuberculosis (TB) spine, a broad spectrum of spine pathologies resemble Pott's spine on MRI and are often missed due to inadequate clinical details. As a result, patients are often subject to unnecessary biopsy. A blinded radiologist may misdiagnose such mimic cases as TB. Our aim is to enable the reader to learn the main criteria that differentiate spine TB from other spine etiologies that mimic TB. A retrospective search was done and authors collected only MRI spine reports that showed a differential diagnosis or diagnosis of TB spine from the computer-based data records of the institution over a four-year period. This revealed 306 cases of TB spine out of which 78 cases with an alternate diagnosis that resembled TB spine were included. We describe a single institute review of 78 such cases that resemble and mimic Pott's spine on MRI. The cases being: (n = 15) pyogenic spondylitis, (n = 1) brucellar spondylodiscitis, (n = 12) rheumatoid arthritis, (n = 12) metastases, (n = 8) lymphoma, (n = 5) post-trauma fractures, (n = 10) degenerative disc disease, (n = 2) Baastrup's disease, (n = 9) osteoporotic fracture, (n = 3) spinal neuropathic arthritis, and (n = 1) case of Rosai-Dorfman disease. The clinical and radiological findings of all these cases were correlated with lab findings and histopathology wherever necessary. Appropriate recognition of these entities that resemble and mimic TB spine on MRI is important for optimal patient care. This paper exposes radiologists to a variety of spine pathologies for which biopsy is not indicated, and highlights key imaging findings of these entities to facilitate greater diagnostic accuracy in clinical practice.
31780859 Tobacco-Derived Lipopolysaccharide, Not Microbial Translocation, as a Potential Contributo 2019 Microbial lipopolysaccharides (LPS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), possibly driving a systemic inflammatory response that may trigger the development and/or exacerbation of the disease. To explore the existence of this mechanism in African RA patients, we have measured systemic levels of LPS and its surrogate, LPS-binding protein (LBP), as well as those of intestinal fatty acid-binding protein (I-FABP), pulmonary surfactant protein D (SP-D), and cotinine in serum to identify possible origins of LPS, as well as associations of these biomarkers with rheumatoid factor (RF) and anticitrullinated peptide (aCCP) autoantibodies and the DAS 28-3 clinical disease severity score. A cohort of 40 disease-modifying antirheumatic drug-naïve, black South African RA patients rated by compound disease scores and 20 healthy subjects and 10 patients with chronic obstructive pulmonary disease (COPD) as controls were included in this study. Levels of the various biomarkers and autoantibodies were measured using a combination of ELISA and immunofluorimetric and immunoturbidometric procedures. LPS levels were lowest in the RA group compared to the healthy controls (p = 0.026) and COPD patients (p = 0.017), while LBP levels were also significantly lower in RA compared to the healthy individuals (p = 0.036). Levels of I-FABP and SP-D were comparable between all three groups. Categorisation of RA patients according to tobacco usage revealed the following significant positive correlations: LBP with C-reactive protein (p = 0.0137); a trend (p = 0.073) towards an association of LBP with the DAS 28-3 disease severity score; RF-IgG antibodies with both LPS and LBP (p = 0.033 and p = 0.041, respectively); aCCP-IgG antibodies with LPS (p = 0.044); and aCCP-IgG with RF-IgM autoantibodies (p = 0.0016). The findings of this study, several of them novel, imply that tobacco products, as opposed to microbial translocation, represent a potential source of LPS in this study cohort of RA patients, again underscoring the risks posed by tobacco usage for the development and severity of RA.
30918031 European Qualitative research project on Patient-preferred outcomes in Early Rheumatoid Ar 2019 Mar 27 INTRODUCTION: Including the patient perspective is important to achieve optimal outcomes in the treatment of rheumatoid arthritis (RA). Ample qualitative studies exist on patient outcomes in RA. A Belgian study recently unravelled what matters most to patients throughout the overwhelming and rapidly evolving early stage of RA. The present study, European Qualitative research project on Patient-preferred outcomes in Early Rheumatoid Arthritis (EQPERA) was created to contribute to a more universal understanding of patient-preferred health and treatment outcomes by integrating the perspectives of patients with early RA from three European countries. METHODS AND ANALYSIS: In EQPERA, a qualitative, explorative, longitudinal study will be implemented in The Netherlands and Sweden, parallel to the methods applied in the previously conducted Belgian study. In each country, a purposive sample of patients with early RA will be individually interviewed 3-6 months after start of the initial RA treatment and subsequently, the same participants will be invited to take part in a focus group 12-18 months after RA treatment initiation. Data collection and analysis will be independently conducted by the local research teams in their native language. A meta-analysis of the local findings will be performed to explore and describe similarities, differences and patterns across countries. ETHICS AND DISSEMINATION: Ethics approval was granted by the responsible local ethics committees. EQPERA follows the recommendations of the Declaration of Helsinki. Two main papers are foreseen (apart from the data reporting on the local findings) for peer-reviewed publication.
31375887 Stiffening of aorta is more preferentially associated with rheumatoid arthritis than perip 2019 Oct The objective of this study is to investigate the relative impact of rheumatoid arthritis (RA) and other factors on arterial stiffness of different regions assessed by regional pulse wave velocity (PWV). Seventy-two patients with RA and 55 strictly matched healthy controls were included. Doppler ultrasound was used to measure the PWV of heart-carotid (hcPWV), heart-femoral (hfPWV), brachial-radial (brPWV), femoral-ankle (faPWV) and carotid-femoral segments (cfPWV) in all subjects. The reproducibility of regional PWV measurement was evaluated in 30 random RA patients. In RA patients, the hfPWV and cfPWV were significantly higher than that in controls (P = 0.0006, P = 0.0001, respectively), and the hcPWV, brPWV and faPWV only showed an increase trend without significance. The mean increase magnitude of hfPWV (17.5%) and cfPWV (18.5%) were greater than brPWV (7.2%) and faPWV (1.7%) in RA patients. The association between RA and both hfPWV, cfPWV remained significant after adjustments for other confounders (P < 0.001). However, the association between RA and brPWV (P = 0.199), faPWV (P = 0.599) was not significant. In addition, age and systolic blood pressure were also significant independent factors associated with hfPWV and cfPWV. The reproducibility analysis showed that hfPWV and cfPWV measurements had lower coefficient of variation than others. The stiffness of different arterial regions is not equally affected by RA. The stiffening of aorta is more preferentially associated with RA than that of the peripheral arteries in extremities. The discrepant stiffening between aorta and peripheral arteries may provide a new insight into the pathogenesis of cardiovascular and microvascular dysfunction frequently occurred in RA.
30221485 Low Persistence Rates in Patients With Rheumatoid Arthritis Treated With Triple Therapy an 2019 Oct OBJECTIVE: Combination treatments for patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX) alone include the addition of a tumor necrosis factor inhibitor (TNFi) or the addition of sulfasalazine (SSZ) and hydroxychloroquine to MTX (triple therapy). We compared persistence and adherence rates between these 2 combination therapies in US veterans and report the reasons for discontinuation of combination treatment in these groups. METHODS: Using Veteran's Affairs clinical and administrative data from 2006 to 2012, veterans with RA escalating treatment from MTX to MTX-TNFi or triple therapy were examined for a 12-month period after combination initiation. Persistence was defined as treatment without a ≥90-day gap in therapy. Adherence was calculated using the proportion of days covered ≥80% at 12 months. Matching weights-adjusted models were applied to more closely mimic randomization in this study. The reasons that patients discontinued their combination regimens were identified by chart abstraction. RESULTS: Full persistence at 1 year was 45% in the MTX-TNFi patients (n = 2,125) and 18% in the triple therapy patients (n = 171) (P < 0.001). Adherence was higher for the MTX-TNFi group (26%) than the triple therapy group (11%) (P < 0.0001). The triple therapy group was associated with significantly more treatment discontinuation, which was most often due to adverse drug events from SSZ. CONCLUSION: Differences in persistence and adherence between the MTX-TNFi and triple therapy groups appear to be primarily related to adverse drug events that were most often attributed to SSZ.
30789850 Prediction of infection risk in rheumatoid arthritis patients treated with biologics: are 2019 May PURPOSE OF REVIEW: There are currently several available biologics for rheumatoid arthritis (RA) with similar efficacy in most trials. A major consideration therefore in choosing a biologic, continues to be safety concerns such as infection. Considerable advances have been made in the understanding of biologic safety on a population level; however, how close are we to stratifying risk for individual patients? This review discusses evidence published in the last year, with reference to key previous literature. RECENT FINDINGS: Comparative safety of biologics has been studied in observational cohorts, with a possible increased risk of serious infection in tocilizumab-treated patients compared with etanercept. Rheumatoid arthritis patients on biologics are often on concomitant medications such as steroids and opioids, and the advances in relation to infection are summarized. Pharmacological biomarkers and optimizing existing risk prediction scores may allow better future risk stratification. SUMMARY: Improved quantification of personalized benefit:harms would allow better-informed decisions, reduction of infection-associated morbidity as well as direct/indirect costs associated with biologics. Although advances have been made to better understand and predict risk, future studies are likely to require a range of novel data sources and methodologies for the goal of precision medicine to be truly realized.
31484730 Monocyte/Macrophage Abnormalities Specific to Rheumatoid Arthritis Are Linked to miR-155 a 2019 Oct 1 Proinflammatory macrophages and miR-155 are increased in patients with rheumatoid arthritis (RA). We studied membrane TNF (mTNF) expression on blood monocytes, polarization into macrophages, miR-155 expression, and the effect of anti-TNF on these biomarkers in RA patients. Sixty-seven RA patients and 109 controls (55 healthy, 54 with spondyloarthritis and connective tissue diseases) were studied. Monocytes were isolated and differentiated into macrophages with or without anti-TNF. mTNF expression was increased on monocytes from RA patients, but not from other inflammatory diseases, correlated with disease activity. Under human serum AB or M-CSF, only monocytes from RA had a defect of differentiation into M2-like macrophages and had a propensity for preferential maturation toward M1-like macrophages that contributed to synovial inflammation. This defect was correlated to mTNF expression and was partially reversed by monoclonal anti-TNF Abs but not by the TNF soluble receptor. miR-155 was increased in M2-macrophages except in adalimumab-treated patients. Transfection of healthy monocytes with miR-155 induced a decrease in M2-like markers, and transfection of RA monocytes with antagomir-155 allowed restoration of M2-like polarization. Defect in differentiation of monocytes into M2-like-macrophages linked to increased miR-155 and correlated with increased mTNF on monocytes could play a key role in RA pathogenesis. Monoclonal anti-TNF Abs but not the TNF soluble receptor partially restored this defect.
31358043 A validated single-cell-based strategy to identify diagnostic and therapeutic targets in c 2019 Jul 30 BACKGROUND: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. METHODS: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. RESULTS: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. CONCLUSIONS: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
31413004 Does immunological remission, defined as disappearance of autoantibodies, occur with curre 2019 Nov OBJECTIVES: Sustained disease-modifying antirheumatic drug (DMARD)-free status, the sustained absence of synovitis after cessation of DMARD therapy, is infrequent in autoantibody-positive rheumatoid arthritis (RA), but approximates cure (ie, disappearance of signs and symptoms). It was recently suggested that immunological remission, defined as disappearance of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), underlies this outcome. Therefore, this long-term observational study determined if autoantibodies disappear in RA patients who achieved sustained DMARD-free remission. METHODS: We studied 95 ACPA-positive and/or RF-positive RA patients who achieved DMARD-free remission after median 4.8 years and kept this status for the remaining follow-up (median 4.2 years). Additionally, 21 autoantibody-positive RA patients with a late flare, defined as recurrence of clinical synovitis after a DMARD-free status of ≥1 year, and 45 autoantibody-positive RA patients who were unable to stop DMARD therapy (during median 10 years) were studied. Anti-cyclic citrullinated peptide 2 (anti-CCP2) IgG, IgM and RF IgM levels were measured in 587 samples obtained at diagnosis, before and after achieving DMARD-free remission. RESULTS: 13% of anti-CCP2 IgG-positive RA patients had seroreverted when achieving remission. In RA patients with a flare and persistent disease this was 8% and 6%, respectively (p=0.63). For anti-CCP2 IgM and RF IgM, similar results were observed. Evaluating the estimated slope of serially measured levels revealed that RF levels decreased more in patients with than without remission (p<0.001); the course of anti-CCP2 levels was not different (p=0.66). CONCLUSIONS: Sustained DMARD-free status in autoantibody-positive RA was not paralleled by an increased frequency of reversion to autoantibody negativity. This form of immunological remission may therefore not be a treatment target in patients with classified RA.
30578852 Pristane-induced arthritis in dark Agouti rat is a relevant model for mimicking vascular d 2019 Jul OBJECTIVES: To understand the pathophysiology of cardiovascular (CV) dysfunction in rheumatoid arthritis (RA) is crucial, but limited by the paucity of animal models able to mimic CV impairments. We wanted to determine if the rat model of Pristane-Induced Arthritis (PIA) reproduced cardiometabolic impairments of RA. METHODS: Dark Agouti rats received an injection of pristane or saline (controls) at day 0. Reactivity to vasoconstrictors and vasodilators was studied in aortic rings and mesenteric arteries at day 28 (acute) and day 120 post-induction (chronic phase). Circulating markers of inflammation, lipid and glucose levels, arthritis and radiographic scores were assessed. RESULTS: In aortic rings, PIA induced a reduced vasoconstriction to phenylephrine and serotonin in both phases of the model. The relaxant effect of acetylcholine was decreased in PIA in acute (P < 0.05) but not in chronic phase. In mesenteric arteries, only the acetylcholine-induced vasorelaxation was impaired in PIA rats in the chronic phase (P < 0.001). Serum interleukin-6 levels were higher, total cholesterol and triglycerides levels were lower in PIA in both phases (P < 0.001) whereas myeloperoxidase activity and blood glucose were unchanged. Adiponectine levels were lower in PIA in acute (P < 0.001) but not in chronic phase. Endothelial function correlated with interleukin-6, total cholesterol levels and arthritis score in aorta but not in mesenteric arteries. CONCLUSIONS: As new information, PIA induces endothelial dysfunction in micro-/macro-vascular beds and low lipid levels, like in RA. This model of chronic arthritis might be useful to study CV pathophysiology and to screen new therapeutic options for reducing CV risk in RA.
30684031 [Etanercept in routine German clinical practice to treat rheumatoid arthritis patients : A 2019 Aug BACKGROUND: The efficacy and safety of the TNF‑α inhibitor etanercept (ETA) as a treatment for rheumatoid arthritis (RA) is well established by randomized controlled trials. The purpose of this study was to evaluate the benefit yielded by ETA within the regular outpatient care. PATIENTS AND METHODS: This prospective non-interventional trial included patients being treated with ETA. Data concerning efficacy, safety and life quality were collected over a period of 52 weeks. Statistical evaluation was done on a solely descriptive level. RESULTS: From 329 specialized medical centres, 4945 patients were enrolled. Of all patients, 94.4% received a co-medication for RA, additionally to their treatment with ETA. At baseline, 22.1% of all patients fulfilled the criteria for functional remission according to the Funktionsfragebogen Hannover (FFbH) questionnaire (95% CI: 21.0-23.3%); at 52 weeks, functional remission rate accounted for 41.1% (last observation carried forward [LOCF], 95% CI: 39.4-42.9%). The disease activity score (DAS) DAS28 declined from 5.4 ± 1.3 (N = 4304) to 3.3 ± 1.4 (as observed; N = 2608). EuroQol EQ-5D, a measurement of health-related life quality issues, indicated an improvement on the visual analogue scale (VAS) from 53.1 ± 21.3 mm (N = 4718) at baseline to 70.0 ± 20.5 mm (as observed; N = 3036). Generally, ETA has been tolerated well. With regard to the safety profile specified by previous studies, no meaningful deviations concerning the nature, frequency or severity of adverse events were detected. CONCLUSION: Based on a large number of patients and in a treatment context that is representative of routine outpatient care in Germany, it was confirmed that patients with RA may benefit from a treatment with ETA.
31137060 Pulmonary Complications of Rheumatoid Arthritis. 2019 Apr Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that characteristically causes joint inflammation and damage. In addition, many patients develop extraarticular manifestations which may cause significant comorbidity and premature mortality.Some respiratory tract involvement of the upper and lower airways and parenchymal disease features are unique to RA, including cricoarytenoid arthritis and RA pulmonary nodulosis, and others, especially the interstitial parenchymal involvement, occur in many other idiopathic and autoimmune diseases. The pathophysiology of lung disease is not well understood. Rheumatoid lung disease may even predate the onset of joint disease, and could be triggered by chronic airway and alveolar epithelial injury. Chronic systemic inflammation and risk factors such as cigarette smoking, infection, host genetics, and immune dysregulation are contributors. Treatment of the respiratory disease is directed at reducing the systemic inflammation of RA. Less well understood is the management of the interstitial lung disease of RA, for which antifibrotic and immune suppressive agents may be helpful. The management of RA-related lung disease is perhaps the major remaining hurdle in reduction of the disease burden related to extraarticular manifestations of this disease.
31037495 Membranous nephropathy caused by rheumatoid arthritis. 2019 Nov Membranous nephropathy (MN) caused by disease-modifying antirheumatic drugs is relatively common in patients with rheumatoid arthritis (RA). However, MN rarely occurs due to RA itself. We describe a 61-year-old woman with RA who showed nephrotic syndrome. She was admitted because of systemic edema and severe arthritis. She had a long history of RA successfully treated with methotrexate (MTX), but discontinued all treatments 4 years before hospitalization. She had never been treated with bucillamine or gold. Laboratory test results were positive for anti-cyclic citrullinated peptide antibody and negative for anti-nuclear antibody. Renal pathologic findings were compatible with MN. Immunofluorescence microscopy showed IgG, IgA, κ, λ, and C3 along the glomerular capillary wall, whereas deposition of IgM or C1q was not detected. In terms of the IgG subclasses, only IgG2 findings were positive. Results for glomerular antigen and serum antibody for M-type phospholipase A2 receptor and thrombospondin type 1 domain-containing 7A were negative. HLA type did not include the HLA-DQA1 gene that is a concern in primary MN (PMN). She responded to intensive immunosuppressive therapy consisting of prednisolone, tacrolimus, and MTX with a parallel reduction of proteinuria. Based on assessments for differentiating PMN from secondary MN (SMN), the diagnosis of the present case was incompatible with PMN. Taken together, we consider that SMN in the present case was due to RA itself rather than drug-induced MN.
30924461 Getting a Grip on Arthritis Online: Responses of rural/remote primary care providers to a 2019 Apr INTRODUCTION: Physicians are often challenged with accessing relevant up-to-date arthritis information to enable the delivery of optimal care. An online continuing medical education programme to disseminate arthritis clinical practice guidelines (CPGs) was developed to address this issue. METHODS: Online learning modules were developed for osteoarthritis (OA) and rheumatoid arthritis (RA) using published CPGs adapted for primary care (best practices), input from subject matter experts and a needs assessment. The programme was piloted in two rural/remote areas of Canada. Knowledge of best practice guidelines was measured before, immediately after completion of the modules and at 3-month follow-up by assigning one point for each appropriate best practice applied to a hypothetical case scenario. Points were then summed into a total best practice score. RESULTS: Participants represented various professions in primary care, including family physicians, physiotherapists, occupational therapists and nurses (n = 89) and demonstrated significant improvements in total best practice scores immediately following completion of the modules (OA pre = 2.8/10, post = 3.8/10, P < 0.01; RA pre = 3.9/12, post = 4.6/12, P < 0.01). The response rate at 3 months was too small for analysis. CONCLUSIONS: With knowledge gained from the online modules, participants were able to apply a greater number of best practices to OA and RA hypothetical case scenarios. The online programme has demonstrated that it can provide some of the information rural/remote primary care providers need to deliver optimal care; however, further research is needed to determine whether these results translate into changes in practice.
31016578 Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Dat 2019 Aug OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.