Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
28605317 Rationalized Insights on Causes of Rheumatoid Arthritis in the Elderly and Women: Special 2017 Rheumatoid arthritis (RA) is an autoimmune disorder distinguished by synovial inflammation followed by destruction of joint. The pathogenesis of arthritis involves immune imbalance of the endogenous system. Causative factors include immune imbalance, oxidative stress, genetics, and environment. Continued effort has been made to treat RA via chemical, enzymatic, genetic, and hormonal approaches. RA has been reported more in the aged and in women. Arthritis necessitates lifelong administration of drugs to maintain quality of life. The major challenges of treatment are the side effects associated with these drugs. Novel approaches and targets have been explored as alternative measures to relieve pain in RA sufferers. Customary treatment strategies have limited therapeutic capability with episodes of associated side effects. Thus, revolutionary advances in novel RA-targeted drug delivery strategies are needed for efficient therapies and to meet the demand for treatment. The current review summarizes the pathogenesis of RA, its causative factors, and therapeutic approaches. These approaches are discussed with regard to mode of action, pharmacokinetics, marketed products, side effects of individual RA drugs, recent developments, modifications in the delivery of various drugs through targeted ligands, novel drug carriers as vesicular, particulate, self assembled, cellular, ceramic systems, and future prospects.
27146888 Self-efficacy and pain acceptance as mediators of the relationship between pain and perfor 2017 Jun OBJECTIVE: To study whether personal factors (self-efficacy and pain acceptance) mediate the relationship between pain and performance of valued life activities in persons with rheumatoid arthritis. METHODS: Persons with rheumatoid arthritis for at least four years ( n = 737; 73% women) answered a questionnaire measuring self-efficacy, pain acceptance, performance of valued life activities, and self-rated pain. Relationships among these constructs were explored using univariate and multivariate analyses. Structural equation modelling was then used to examine the mediational role of personal factors on the relationship between pain and performance of valued life activities. RESULTS: A direct negative association between pain and performance of valued life activities was identified ( Beta = .34, P < .001). This suggests that people with rheumatoid arthritis who had higher levels of pain has increased difficulties in performing valued life activities. Self-efficacy and activity engagement component of pain acceptance mediated the relationship between pain and performance of valued life activities, however the pain willingness component of pain acceptance did not influence participation in valued life activities. CONCLUSION: These findings highlight the importance of considering personal factors, such as pain acceptance and self-efficacy, in facilitating participation in valued life activities.
28138707 Lnc‑IL7R promotes the growth of fibroblast‑like synoviocytes through interaction with 2017 Mar Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease that affects ~1% of the world's population. Although the precise mechanism of RA has yet to be elucidated, accumulating evidence suggests that fibroblast‑like synoviocytes (FLSs) serve critical roles in the initiation and progression of RA. However, the underlying molecular mechanisms of FLS proliferation have yet to be elucidated. Long noncoding‑interleukin‑7 receptor (lnc‑IL7R) has been recently identified, which is activated by lipopolysaccharide (LPS) stimulation and diminishes the LPS‑induced inflammatory response. In the present study, gain‑ and loss‑of‑function assays were performed in order to investigate the role of lnc‑IL7R in FLS. It is demonstrated, to the best of the authors' knowledge for the first time, that lnc‑IL7R promotes cell proliferation, cell cycle progression and inhibits apoptosis in FLS. Further investigation identified that lnc‑IL7 interacts with enhancer of zeste homolog 2 (EZH2) and is required for polycomb repressive complex 2 (PRC2)‑mediated suppression, including cyclin‑dependent kinase inhibitor 1A and cyclin‑dependent kinase inhibitor 2A. Lnc‑IL7R may be a promising therapeutic target for the treatment of RA.
28419881 The Effects of Clinical Factors and Retro-Odontoid Soft Tissue Thickness on Atlantoaxial I 2017 Jul BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that often occurs in the atlantoaxial segment of the cervical spine and results in instability that can cause severe pain and neurologic symptoms. Thickening of soft tissue posterior to the odontoid process of the atlantoaxial segment is referred to as retro-odontoid soft tissue (ROST) thickness or pseudotumor. The mechanism of ROST thickness is still unknown. METHODS: Among patients diagnosed with RA, those with cervical radiographs and magnetic resonance imaging records were selected for investigation of their clinical symptoms, laboratory findings, radiologic evaluation, and RA medication history. RESULTS: A total of 199 patients were selected and divided into lower and upper median groups according to the ROST thickness value. In patients with RA, the median ROST thickness value was 2.3 mm (interquartile range, 1.4-3.4). The median value of the anterior atlanto-dens interval (ADI) was 2.4 mm, with a significant difference being observed between the lower and upper median ROST thickness groups (P = 0.001). Multivariable linear regression analysis revealed a correlation between Steinbrocker stage and the positivity of rheumatoid factor. For each unit increase in the Steinbrocker stage, the ROST thickness increased by 0.35 mm (β, -0.349; 95% confidence interval -0.643 to -0.055; P = 0.020). For every 1-mm increase in the ADI, ROST thickness decreased by 0.16 mm (β, -0.163; 95% confidence interval -0.264 to -0.062; P = 0.002). CONCLUSIONS: This study showed a statistical correlation between ROST thickness and ADI related to biomechanical changes in the dynamic atlantoaxial segment, thereby suggesting the value of a prospective study.
28901303 Role of collagen triple helix repeat containing-1 in tumor and inflammatory diseases. 2017 Initially, collagen triple helix repeat containing-1 (CTHRC1) is expressed mainly in adventitial fibroblasts and neointimal smooth muscle cells of balloon-injured vessels, and increases cell migration, promotes tissue repair in response to injury. A variety of studies demonstrated that over-expression of CTHRC1 in solid tumors results in enhancement of migration and invasion of tumor cells, and is associated with decreased overall survival and disease-free survival. CTHRC1 expression is elevated in hepatitis B virus-infected patients and highly correlated with hepatocellular carcinoma progression as well. Furthermore, CTHRC1 plays a pivotal role in a great many fields, including increases bone mass, prevents myelination, reverses collagen synthesis in keloid fibroblasts, and increases fibroblast-like synoviocytes migration speed and abundant production of arthritic pannus in rheumatoid arthritis. Therefore, it will provide new insight into the pathogenesis of tumor and autoimmune diseases, and will shed new light on the therapy of related clinical diseases.
29265872 Stress in patients diagnosed with rheumatoid arthritis compared to chronic pain. 2017 Nov PURPOSE/OBJECTIVE: To examine potential differences in cognitions and traitlike factors that relate to stress among individuals diagnosed with rheumatoid arthritis (RA) compared to those with chronic pain (CP). Research Method/Design: A cross-sectional study was conducted with participants recruited from outpatient rheumatology and CP clinics. Participants completed self-report questionnaires of demographics, disease characteristics, cognitions, and traitlike constructs. Correlates of patient stress were considered using hierarchical multiple regression. RESULTS: Analyses included 445 participants: 226 patients diagnosed with RA and 229 patients diagnosed with CP. In participants with RA, excessive worrying and anxiety sensitivity were independently associated with feeling stressed (p < .001), and 29% of the variance in stress scores was explained after adjusting for age, gender, years of education, and average pain intensity. In participants with CP, fear of relaxation, anxiety sensitivity, and pain catastrophizing were independently associated with feeling stressed (p < .001), and 31% of variance in stress scores was explained after adjusting for age, gender, years of education, and average pain intensity. Comparison of the fit of the model in both groups of patients through use of Fisher's z test found that the set of variables did similarly well for both patients with RA and those with CP, with no significant difference between R2 values (z = .88, p = .388). CONCLUSIONS/IMPLICATIONS: This study establishes cognitions and traitlike factors that are related to reports of stress among patients with RA and CP. These factors should be considered when treating and developing interventions for patients who experience increased feelings of stress. (PsycINFO Database Record
28214924 Characteristics and outcomes of rheumatoid arthritis patients who started biosimilar infli 2017 Jun To compare the characteristics of rheumatoid arthritis (RA) patients receiving either biosimilar or originator infliximab and to identify the effectiveness and safety of biosimilar infliximab in RA patients in real-world practice. RA patients who started either biosimilar or originator infliximab were selected using the prospective biologic disease-modifying anti-rheumatic drugs (DMARDs) registry: BIOlogics Pharmacoepidemiologic StudY (BIOPSY). Baseline characteristics of the two groups were compared, and short-term treatment outcomes, including DAS28-ESR and HAQ-DI scores, were compared after initiation of biosimilar or originator infliximab. The drug retention rates of the two groups were also compared. A total of 100 RA patients, 55 biosimilar, and 45 originator infliximab users were included in this analysis. Baseline characteristics of age, disease duration, and previous or current medications were similar in the two groups. Baseline DAS28-ESR was higher in the originator infliximab group (6.3 ± 1.1 vs. 5.8 ± 1.1, p = 0.02). The early DAS28-ESR remission rates observed 7.9 ± 1.8 months after starting biosimilar and originator infliximab were 15.0 and 25.0%, respectively (p = 0.47). The change in HAQ-DI did not differ between the two groups (0.4 ± 0.7 vs. 0.4 ± 0.8, p = 0.94). Patients treated with biosimilar infliximab in clinical practice had lower disease activity at the start of treatment than those receiving originator infliximab. Biosimilar infliximab was well-tolerated, safe, and of similar clinical effectiveness to originator infliximab. Larger number of patient and longer follow-up data will be needed to confirm the effectiveness and safety of biosimilar infliximab in clinical practice.
28438483 What role does rheumatoid arthritis disease activity have in cardiovascular risk? 2018 Nov Rheumatoid arthritis (RA) is associated with a 1.3 to 3-fold increase in mortality, being the major cause of death from cardiovascular complications (40%-50%). Therefore, the initial approach should include cardiovascular risk (CVR) assessment using algorithms adapted for this population. Although, SCOREM is an important advance, there are data indicating that subclinical atherosclerosis may be underdiagnosed. OBJECTIVE: To estimate the strength of association between carotid ultrasound and SCOREM in this population, as well as the implication of disease activity. METHODOLOGY: Cross-sectional, observational, analytical study performed at the General Hospital of Ciudad Real, Spain, between June 2013 and May 2014. The evaluation of CVR was performed and, according to SCOREM, the population was divided into low and high (medium, high and very high) risk. We studied the presence of subclinical atherosclerosis in low-risk patients. RESULTS: Of the total of 119 RA patients, 73.1% had traditional risk factors. Thirty-eight patients were excluded because of a previous cardiovascular event, diabetes mellitus and/or nephropathy. Atheromatous plaque was observed in 14.63% of the low-risk population. The factor with the strongest association to the presence of subclinical atherosclerosis was a moderate or high activity of RA measured by the simplified disease activity index with an odds ratio of 4.95 (95% CI: 1.53-16.01). CONCLUSIONS: Although there was an acceptable correlation between the presence of subclinical atherosclerosis and SCOREM, there was a considerable proportion of atheromatous plaques in low-risk patients. Disease activity was the risk factor most closely associated with increased CVR.
28569212 The prevalence of ACPA is lower in rheumatoid arthritis patients with an older age of onse 2017 May 31 BACKGROUND: Rheumatoid arthritis (RA) consists of two syndromes, one autoantibody-positive and one autoantibody-negative. Existing data on the relation between age of onset and prevalence of autoantibodies were conflicting. Therefore this multicohort study assessed the age of onset in relation to the presence of autoantibodies. The association with characteristics of the anti-citrullinated protein antibodies (ACPA) response was also explored. METHODS: The 1987 criteria-positive RA patients included in the Leiden EAC, BARFOT, ESPOIR, Umeå and Lund cohorts (n = 3321) were studied at presentation for age of onset and the presence of ACPA, rheumatoid factor (RF) and anti-carbamylated protein (anti-CarP) antibodies. Logistic regression analyses were performed; effect sizes were summarized in inverse-weighted meta-analyses. Within ACPA-positive RA, ACPA level was studied in all cohorts; ACPA isotypes, ACPA fine specificity and ACPA avidity index and clinical characteristics were studied in the Leiden EAC. RESULTS: From the age of 50 onward, the proportion of ACPA-negative RA patients increased with age in the five cohorts. Similar observations were made for RF and anti-CarP. The composition of the ACPA response did not change with increasing age of onset with respect to titer, isotype distribution, fine specificity and avidity index. With increasing age of onset, RA patients smoked less often, had higher acute phase reactants and more often had a sub(acute) symptom onset. CONCLUSIONS: Data of five cohorts revealed that with older age of onset ACPA-negative RA is more frequent than ACPA-positive RA, while characteristics of ACPA-positive RA as judged by the composition of the ACPA response appeared not age dependent. Further biologic studies are needed to characterize the pathogenesis of ACPA-negative polyarthritis at older age and to promote personalized treatment decisions in ACPA-negative patients in daily practice.
28793911 IgG Fc galactosylation predicts response to methotrexate in early rheumatoid arthritis. 2017 Aug 9 BACKGROUND: Methotrexate (MTX) is the standard first-line therapy in rheumatoid arthritis (RA) with variable clinical efficacy that is difficult to predict. The glycosylation status of immunoglobulin G (IgG) is altered in RA and influenced by MTX treatment. We aimed to further investigate if IgG glycosylation in untreated early RA can predict therapeutic response to MTX. METHODS: We used a shotgun proteomic approach to screen for the Fc glycopeptides in the serum of 12 control subjects and 59 untreated patients with early RA prior to and following MTX initiation. MTX treatment response was defined according to the European League Against Rheumatism at a median of 14 weeks (range 13-15) after treatment initiation. Seropositive patients were defined as those testing positive for anticitrullinated protein antibodies and/or rheumatoid factor at baseline (n = 44). Data analysis was performed using uni- and multivariate statistics. RESULTS: We could confirm a low abundance of galactosylated glycans in untreated patients with early RA compared with control subjects that was partially restored by MTX treatment. This was more evident among future nonresponders than among responders to MTX treatment. Results were further validated and confirmed by multivariate statistical analysis of the baseline Fc glycan, proteomic, and clinical data. We found that the ratio between the main agalactosylated (FA2) and main mono- and di-galactosylated Fc glycans (FA2G1 and FA2G2) of IgG1 ranked as the most prominent factor distinguishing responders from nonresponders. A low baseline ratio of FA2/[FA2G1 + FA2G2]-IgG1 was associated with nonresponse (OR 5.3 [1.6-17.0]) and was able to discriminate future nonresponders from responders to MTX therapy with a sensitivity of 70% (95% CI 46-88%) and a specificity of 69% (95% CI 52-83%). For seropositive patients (n = 44), this trend was improved with a sensitivity of 73% (95% CI 45-92%) for nonresponse and a specificity of 79% (95% CI 60-92%). CONCLUSIONS: We show that the FA2/[FA2G1 + FA2G2] of IgG1 is a biomarker candidate that is significantly associated with nonresponding patients and has potential value for prediction of MTX clinical response.
29282619 Dickkopf 1 protein circulating levels as a possible biomarker of functional disability and 2018 Mar Rheumatoid arthritis (RA) is an inflammatory disease characterized by joint destruction, deformity, lower functionality, and decrease in life expectancy. Wingless signaling pathway (Wnt) has been recently involved in bone homeostasis. Studies suggest that overexpression of the pathway inhibitors, like the Dickkopf 1 protein (DKK1), has been implicated in bone destruction. The objective of this study is to compare circulating levels of DKK1 in different groups of patients with disease activity (remission, low, moderate, high activity,) and functionality status. Three hundred seventy-nine patients with RA were evaluated between March 2015 and November 2016. Disease activity was evaluated by disease activity score 28 with C-reactive protein (DAS28CPR), simplified and clinical disease activity scores (SDAI, CDAI), routine assessment of patient index data 3 (RAPID3), functional status using Multidimensional Health Assessment Questionnaire (MD-HAQ), and the Steinbrocker functional classification. DKK1 levels were measured by ELISA. The mean age was 60.7 ± 13.9 years. Disease duration was 13.2 ± 10.9 years. Higher levels of DKK1 were not associated with disease activity by CDAI (p = 0.70), SDAI (p = 0.84), DAS28CRP (p = 0.80), or RAPID3 (p = 0.70). Interestingly higher levels of DKK1 were significantly associated to lower functional status evaluating by the Steinbrocker classification (p = 0,013), severe disability by MD-HAQ (p = 0,004), and variables associated with joint destruction like osteoporosis, higher titles of rheumatoid factor, smoking, and increased hospital admissions related to RA. Higher levels of DKK1 were found in patients with lower functional status. This association was not found in patients with greater disease activity by CDAI, SDAI, DAS28, and RAPID3. This could be explained by more structural damage; DKK1 could be used as a biomarker of joint destruction in RA.
29126434 Whole blood microRNA expression pattern differentiates patients with rheumatoid arthritis, 2017 Nov 10 BACKGROUND: Epigenetic mechanisms can integrate gene-environment interactions that mediate disease transition from preclinical to clinically overt rheumatoid arthritis (RA). To better understand their role, we evaluated microRNA (miRNA, miR) expression profile in indigenous North American patients with RA who were positive for anticitrullinated protein antibodies; their autoantibody-positive, asymptomatic first-degree relatives (FDRs); and disease-free healthy control subjects (HCs). METHODS: Total RNA was isolated from whole blood samples obtained from HC (n = 12), patients with RA (n = 18), and FDRs (n = 12). Expression of 35 selected relevant miRNAs, as well as associated downstream messenger RNA (mRNA) targets of miR-103a-3p, was determined by qRT-PCR. RESULTS: Whole blood expression profiling identified significantly differential miRNA expression in patients with RA (13 miRNAs) and FDRs (10 miRNAs) compared with HCs. Among these, expression of miR-103a-3p, miR-155, miR-146a-5p, and miR-26b-3p was significantly upregulated, whereas miR-346 was significantly downregulated, in both study groups. Expression of miR-103a-3p was consistently elevated in FDRs at two time points 1 year apart. We also confirmed increased miR-103a-3p expression in peripheral blood mononuclear cells from patients with RA compared with HCs. Predicted target analyses of differentially expressed miRNAs in patients with RA and FDRs showed overlapping biological networks. Consistent with these curated networks, mRNA expression of DICER1, AGO1, CREB1, DAPK1, and TP53 was downregulated significantly with miR-103a-3p expression in FDRs. CONCLUSIONS: We highlight systematically altered circulating miRNA expression in at-risk FDRs prior to RA onset, a profile they shared with patients with RA. Prominently consistent miR-103a-3p expression indicates its utility as a prognostic biomarker for preclinical RA while highlighting biological pathways important for transition to clinically detectable disease.
27726046 Comparative effectiveness of biologics for the management of rheumatoid arthritis: systema 2017 Jan Our aim was to establish the comparative effectiveness of rheumatoid arthritis (RA) biologics, using a systematic review and network meta-analysis. The systematic review used randomized controlled trials (RCTs) in adults with RA who failed treatment with conventional disease-modifying agents for rheumatoid disease (cDMARDs). We compared the effectiveness of abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, and rituximab to tocilizumab, a recent biologic with a different mechanism of action (anti-IL-6 receptor). A network meta-analysis (NMA) included the indirect and direct evidence previously selected. In total, 207 articles were included describing 68 RCTs. The NMA showed that tocilizumab monotherapy was superior to standard care (ACR20, OR 13.27, 95 % CrI [3.958, 43.98]; ACR50, 17.45 [10.18, 31.24]; ACR70, 37.77 [7.226, 216.3]; EULAR, 10.42 [1.963, 54.8]); and methotrexate (MTX; ACR50, OR 5.44 [4.142, 7.238]; ACR70, 7.364 [1.4, 30.83]; EULAR, 4.226 [1.184, 15.58]) at 26 weeks. Similarly, the combination of tocilizumab + MTX was significantly better than standard care/placebo and MTX alone for ACR20, ACR50, ACR70, and EULAR at 26 weeks (OR 18.63 [5.32, 66.81]; 24.27 [14.5, 41.91]; 46.13 [10.08, 277]; 14.23 [2.493, 84.02]; 4.169 [2.267, 7.871]; 5.44 [4.142, 7.238]; 8.731 [4.203, 19.29]; 7.306 [4.393, 13.04], respectively). At 52 weeks, compared to MTX alone, tocilizumab + MTX was significantly better for ACR20 and ACR50 response. Few significant differences were found between tocilizumab (alone or in combination) and any other biologics. Results must be considered in context with the limitations of the available evidence. This NMA suggests that tocilizumab was superior to cDMARDs and as effective as other biologics for RA.
28860666 Features of cardiac remodeling in Patients with Acute Coronary Syndrome Complicated with R 2017 Aug 31 Cardiovascular diseases are important factors to increased morbidity and mortality in patients with rheumatoid arthritis (RA). The aim of this study is to investigate the effects of RA on cardiac remodeling in patients with acute coronary syndrome (ACS). Sixty-one patients with ACS complicated with RA (RA group) and 55 age- and sex-matched patients with ACS without RA (control group) were enrolled. We compared the parameters of laboratory and echocardiogram across the 2 groups. Levels of serum brain natriuretic peptide in patients with RA were significantly higher than control group. Prevalence of left ventricular hypertrophy (LVH), and LV diastolic dysfunction (E/A < 1) were significantly higher in the RA patients, while the LV ejection fraction (EF%) was significantly lower in RA patients. Incidence of tricuspid regurgitation and pulmonary regurgitation were significantly higher in ACS patients with RA than in the ACS patients without RA. In RA group, levels of serum high density lipoprotein cholesterol were negatively correlated with C reactive protein (CRP), EF% was also negatively correlated with CRP. The prevalence of LVH and mitral regurgitation showed positive correlations with ESR. Early intervention for controlling the inflammation associated with RA can play a significant role in preventing cardiac remodeling in ACS patients.
28393498 Impact of Obesity and Adiposity on Inflammatory Markers in Patients With Rheumatoid Arthri 2017 Dec OBJECTIVE: The C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are important disease activity biomarkers in rheumatoid arthritis (RA). This study aimed to determine to what extent obesity biases these biomarkers. METHODS: Body mass index (BMI) associations with CRP level and ESR were assessed in 2 RA cohorts: the cross-sectional Body Composition (BC) cohort (n = 451), including whole-body dual x-ray absorptiometry measures of fat mass index; and the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA) registry (n = 1,652), using multivariable models stratified by sex. For comparison, associations were evaluated in the general population using the National Health and Nutrition Examination Survey. RESULTS: Among women with RA and in the general population, greater BMI was associated with greater CRP levels, especially among women with severe obesity (P < 0.001 for BMI ≥35 kg/m(2) versus 20-25 kg/m(2) ). This association remained after adjustment for joint counts and patient global health scores (P < 0.001 in BC and P < 0.01 in VARA), but was attenuated after adjustment for fat mass index (P = 0.17). Positive associations between BMI and ESR in women were more modest. In men with RA, lower BMI was associated with higher CRP levels and ESR, contrasting with positive associations among men in the general population. CONCLUSION: Obesity is associated with higher CRP levels and ESR in women with RA. This association is related to fat mass and not RA disease activity. Low BMI is associated with higher CRP levels in men with RA; this unexpected finding remains incompletely explained but likely is not a direct effect of adiposity.
28102443 [New options for the practice : Update S1/S2 guidelines on rheumatoid arthritis?]. 2017 Mar Guidelines are important tools for evidence-based pharmacological treatment of patients suffering from rheumatoid arthritis. Recommendations assist physicians in identifying the best form of treatment but ultimately, the final decision is based on joint participation by the patient and physician. Nowadays, general concepts, such as treat to target seem to be more important in rheumatoid arthritis than differencies between various drugs or drug classes. The universal recommendation to use methotrexate as the initial disease-modifying antirheumatic drug (DMARD) is driven more by economic reasons than by scientific data, which is not completely wrong but should be disclosed. For the future, more differentiated recommendations need better individual risk stratification and more distinct profiling of the different substances.
28658301 The effect of anti-rheumatic medications for coronary artery diseases risk in patients wit 2017 OBJECTIVES: To determine whether anti-rheumatic drug usage is associated with risk of coronary artery diseases (CAD) in incident Rheumatoid Arthritis (RA) patients. METHODS: Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 6260 patients who were newly diagnosed with RA between 2001-2010. The study endpoint was occurrence of CAD according to the ICD-9-CM codes. We used the WHO Defined Daily Dose (DDD) as a tool to assess the drugs exposure. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease after controlling for demographic and other co-morbidities. When the proportionality assumption is violated, a spline curve of the Scaled Schoenfeld residuals is fitted to demonstrate the estimated effect on CAD over time for drug usage. RESULTS: Among RA patients, use of celecoxib, and etoricoxib was associated with significantly decreased incidence of CAD. The adjusted HR(95% CI) of CAD for low-dose celecoxib (DDD≦1) and high-dose user were 0.47(0.34, 0.65) and 0.37(0.24, 0.58) during the 4 year follow-up time; however, it became 0.98(0.70, 1.37) and1.29(0.85, 1.95). Adjusted HR(95% CI) of CAD for etoricoxib users remained 0.47(0.26, 0.84). CONCLUSIONS: This study revealed association of decreased CAD risk in RA patients taking 2 different kinds of COX-2i in comparison with nonusers. The effect might be changed over time, after about 4 years.
28931886 Value of Measuring Anti-Carbamylated Protein Antibodies for Classification on Early Arthri 2017 Sep 20 Classification of patients with rheumatoid arthritis (RA) as quickly as possible improves their prognosis. This reason motivates specially dedicated early arthritis (EA) clinics. Here, we have used 1062 EA patients with two years of follow-up to explore the value of anti-carbamylated protein (anti-CarP) antibodies, a new type of RA specific autoantibodies, for classification. Specifically, we aimed to determine whether the addition of anti-CarP antibodies to IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are helpful in RA classification, improves it or not. Our analysis showed that incorporation of the anti-CarP antibodies to combinations of the other two antibodies (all joint by the OR Boolean operator) produces a modest increase in sensitivity (2.2% higher), at the cost of decreased specificity (8.1% lower). The cost-benefit ratio was more favorable in the patients lacking the other autoantibodies. However, it did not improve by considering different titer levels of the anti-CarP antibodies, or after exhaustively exploring other antibody combinations. Therefore, the place in RA classification of these antibodies is questionable in the context of current treatments and biomarkers. This conclusion does not exclude their potential value for stratifying patients in joint damage, disease activity, disability, or mortality categories.
27988396 Total sesquiterpene lactones prepared from Inula helenium L. has potentials in prevention 2017 Jan 20 BACKGROUNDS: Inula helenium L. is an herb with anti-inflammatory properties. Sesquiterpene lactones (SLs), mainly alantolactone (AL) and isoalantolactone (IAL), are considered as its active ingredients. However, the anti-inflammatory effects of SL-containing extracts of I. helenium have not been explored. Here we prepared total SLs from I. helenium (TSL-IHL), analyzed its chemical constituents, and performed cellular and animal studies to evaluate its anti-inflammatory activities. MATERIALS AND METHODS: The chemical profile of TSL-IHL was analyzed by HPLC-UV. Its in vitro effects on the activation of signaling pathways and expression of inflammatory genes were examined by western blotting and quantitative real-time PCR, respectively, and compared with those of AL and IAL. Its in vivo anti-inflammatory effects were evaluated in adjuvant- and collagen-induced arthritis rat models. RESULTS: Chemical analysis showed that AL and IAL represent major constituents of TSL-IHL. TSL-IHL, as well as AL and IAL, could inhibit TNF-α-induced activation of NF-κB and MAPK pathways in b. End3 cells, suppress the expressions of MMP-3, MCP-1, and IL-1 in TNF-α-stimulated synovial fibroblasts, and IL-1, IL-6, and iNOS in LPS-activated RAW 264.7 cells in a dose-dependent manner in the range of 0.6-2.4μg/mL. Oral administration of TSL-IHL at 12.5-50mg/kg could dose-dependently alleviate the arthritic severity and paw swelling in either developing or developed phases of arthritis of rats induced by adjuvant or collagen CONCLUSIONS: These results indicated potentials of TSL-IHL in prevention and therapy of rheumatoid arthritis.
28926162 Retinal vessel morphology in rheumatoid arthritis: Association with systemic inflammation, 2017 Nov OBJECTIVE: Quantification of retinal vessel morphology has emerged as a marker of cardiovascular health. We examined retinal microvascular diameters in RA, particularly in regard to systemic inflammation, subclinical atherosclerosis, and cardiovascular risk. METHODS: Retinal images from RA patients and controls were processed using computerized software, to obtain CRAE and CRVE and AVR. Subclinical atherosclerosis was assessed with cIMT, and 10-year risk of general cardiovascular disease was calculated. RESULTS: Both CRAE (78.8 ± 8.9 vs 90.2 ± 9.9 μm, P < .001) and AVR (0.69 ± 0.09 vs 0.81 ± 0.09, P < .001) were decreased in RA patients (n = 87) compared to controls (n = 46), whereas CRVE did not differ. Among RA patients, CRAE and AVR were inversely associated with both cIMT and CRP, whereas CRVE positively correlated with CRP (P < .05 for all). CRAE additionally correlated with cardiovascular risk score (r = -.396, P = .001). In the multivariate analysis, cardiovascular risk was associated with CRAE; age with CRVE, while CRP independently predicted AVR. CONCLUSIONS: Our study shows altered retinal microvascular morphology in RA patients. Inflammation appears as the biological link for the observed association between retinal microvascular abnormalities and subclinical atherosclerosis. Retinal arteriolar narrowing might play its own role in cardiovascular risk prediction in RA.