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ID PMID Title PublicationDate abstract
29787856 The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors 2018 Oct Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22-4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01-2.53]) and severity of fatigue (OR 1.26 95% CI 1.15-1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one's capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.
29623390 The role of genetics and epigenetics in rheumatic diseases: are they really a target to be 2018 Aug To date, numerous genetic and epigenetic studies have been performed and provided a crucial step forward in our understanding of the pathogenesis of rheumatic diseases. However, most of the recent advances in the treatment of rheumatic diseases including biological therapies are not based on or even discrepant from these genetic and epigenetic findings. For example, tumor necrosis factor inhibitors are quite successful in the treatment of rheumatoid arthritis (RA), Behçet's disease (BD), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) but not in that of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV), conversely, RA shares genetic backgrounds more with SLE, SSc, SS and AAV than BD, AS and PsA. In this review, we briefly highlight the findings from recent genetic and epigenetic studies and discuss what needs to be studied to provide a novel, more efficacious management of rheumatic diseases.
29656791 Cardiovascular risk factors predicting cardiac events are different in patients with rheum 2018 Dec OBJECTIVES: Increased cardiovascular risk in rheumatoid arthritis (RA) is well established. Examining traditional cardiovascular risk factors alone underestimates cardiovascular risk in RA. Systematic inflammation, measured by erythrocyte sedimentation rate or C-reactive protein is also a major risk factor. However, the contribution of traditional cardiovascular risk factors (such as obesity and hyperlipidaemia) compared to inflammation is uncertain in psoriatic arthritis (PsA) and RA. We examine the incidence of major adverse cardiac events (MACE) among patients with RA, PsA psoriasis, and controls adjusting for risk factors, inflammation and disease modifying anti-rheumatic drug treatment, to better define cardiovascular risk. METHODS: Using the Secure Anonymised Information Linkage databank, comprising routinely collected Welsh health data from 1999 to 2013, the incidence and first occurrence of a MACE in individuals with RA (n = 8650), PsA (n = 2128) and psoriasis (n = 24,630) compared to controls (n = 11,87,706) was investigated. RESULTS: Traditional cardiovascular risk factors are higher in RA, PsA and psoriasis than controls. After adjusting for these factors, additional cardiovascular risk was only significantly increased in female RA patients (HR = 1.3; 95% CI: 1.0-1.7; p = 0.05) and psoriasis (HR = 1.2; 95% CI: 1.0-1.4; p = 0.02) but not statistically significant for PsA (HR = 1.5; 95% CI: 0.9-2.5; p = 0.13). ESR and CRP were increased in patients with RA but not in patients with psoriasis. CONCLUSION: Additional increased cardiovascular risk was observed in female RA and psoriasis but not PsA. Systematic inflammation is higher in RA but not psoriasis, indicating that there are varying mediators of cardiovascular risk across these conditions.
29294598 Rapid onset of efficacy predicts response to therapy with certolizumab plus methotrexate i 2018 Nov BACKGROUND/AIMS: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSION: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.
29676517 Impact of Changes in Inflammation on Estimated Ten-Year Cardiovascular Risk in Rheumatoid 2018 Sep OBJECTIVE: Current validated cardiovascular (CV) risk estimates were developed in populations with relatively stable levels of inflammation, whereas patients with rheumatoid arthritis (RA) routinely experience significant changes in inflammation. This study was undertaken to test whether changes in inflammation affect estimated CV risk as measured using validated population-based risk calculators. METHODS: Participants in a prospective RA cohort who experienced a decrease or an increase of ≥10 mg/liter in the C-reactive protein (CRP) level at 2 consecutive time points 1 year apart (CRP decrease group and CRP increase group, respectively) were included in this study. We estimated 10-year CV risk using the following calculators: Framingham Risk Score, 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Score, Reynolds Risk Score (RRS), and QRISK2. Of these calculators, only the RRS includes a variable addressing the CRP level. Paired t-tests were performed to compare risk scores at baseline and 1-year follow-up. We calculated the correlations between the changes in risk scores and changes in pro-B-type natriuretic peptide (pro BNP), a surrogate marker of CV risk. RESULTS: One hundred eighty RA patients were included in the study (mean age 57.8 years, 84% female, 80% seropositive). Of the calculators studied, only the RRS was sensitive to changes in inflammation; an increase in inflammation was associated with increased estimated CV risk (P < 0.0001), and only the RRS was correlated with changes in proBNP (r = 0.17, P = 0.03). CONCLUSION: Our data showed no significant change in CV risk estimated using validated general population CV risk calculators except for the RRS. These findings suggest that CV risk may be modulated by changes in inflammation in RA, which is not typically considered when using existing CV risk calculators.
29533757 Cause-specific mortality in a large population-based cohort of patients with rheumatoid ar 2018 Jul OBJECTIVES: The aim of our study was to investigate cause-specific mortality in rheumatoid arthritis (RA) subjects living in Italy. METHODS: We identified in the electronic archive of the Veneto Region patients aged 20-89 years who were exempt from co-payment for RA in January 2010, and linked them with the archive of causes of deaths of the period 2010-2015. Causes of death were coded according to the International Classification of Diseases, 10th Edition. Standardised mortality ratios (SMRs) with 95% confidence intervals were computed as the ratios between deaths observed in the cohort, and those expected according to age- and gender-specific regional mortality rates. RESULTS: Overall, 16,098 residents diagnosed with RA and aged 20-89 years were enrolled in the cohort. The overall follow-up amounted to 88,599 person-years, with 2,142 registered decedents. The most common causes of death were circulatory diseases (36.6%), neoplasms (24.2%), and respiratory diseases (8.3%). Overall mortality was increased in RA subjects (SMR=1.42, confidence interval 1.36-1.48). Mortality was significantly increased from circulatory (SMR=1.56, 1.45-1.67), respiratory (SMR=1.83, 1.57-2.12), digestive (SMR=1.93, 1.60-2.32), infectious (SMR=2.34, 1.88-2.89), haematological diseases (SMR=3.22, 2.04-4.83), and falls (SMR=1.95, 1.19-3.01). RA was the underlying cause of death in 6.1% of all deaths in the cohort and was mentioned in 25.4% of death certificates. CONCLUSIONS: In our study, a 42% excess risk of death was observed among subjects with RA compared with the general population. Cardiovascular disease is the primary cause of premature death in RA. Adverse effects of therapy and comorbidities should be adequately monitored in RA subjects.
29875338 Analysis of Socioeconomic Status in the Patients with Rheumatoid Arthritis. 2018 Jun 7 Rheumatoid arthritis (RA) is a systemic inflammatory disease with different etiologies in different areas. Our study focused on the prevalence of RA in Taiwan from 2001 to 2011. This study contained longitudinal enrollment files, claims data, catastrophic illness files, and treatment registries from Taiwan Longitudinal Health Insurance Research Database. We identified RA patients by ICD-9-CM code 714.0. The demographical variables including age, sex, income and area of registration were evaluated. The multivariate Poisson regression was applied to calculate relative risk for developing RA. In Taiwan, the ratio of female to male was about 5:1. From 2001 to 2011, significant increasing prevalence of RA, from 0.07% to 0.14%, was found in women. The prevalence of RA was increasing 6% per year in both sex groups. The annual incidence rate (per 10,000 person years) ranged from 1.62 to 2.02 (female: 2.30⁻3.14; male: 0.71⁻1.17) from 2003 to 2011. City area had lowest incidence rate of RA compared with suburban or rural area. Higher incidence of RA was observed among lower socioeconomic status. The prevalence of RA was rising from 0.07% in 2001 to 0.14% in 2011. Incidence was about 2/10,000 person-years and female to male ratio was 5:1. Lower socioeconomic status and living rural region might be a risk factor for developing RA.
29764964 Cardiovascular (CV) Risk after Initiation of Abatacept versus TNF Inhibitors in Rheumatoid 2018 Aug OBJECTIVE: To evaluate the cardiovascular safety of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients with and without underlying cardiovascular disease (CVD). METHODS: We identified RA patients with and without baseline CVD who initiated ABA or TNFi by using data from 2 large US insurance claims databases: Medicare (2008-2013) and Truven MarketScan (2006-2015). After stratifying by baseline CVD, ABA initiators were 1:1 propensity score (PS) matched to TNFi initiators to control for > 60 baseline covariates. Cox proportional hazards regression estimated the HR and 95% CI for a composite endpoint of CVD including myocardial infarction, stroke/transient ischemic stroke, or coronary revascularization in the PS-matched cohorts. HR from 2 databases were combined through an inverse variance-weighted fixed-effects model. RESULTS: We included 6102 PS-matched pairs of ABA and TNFi initiators from Medicare and 6934 pairs from MarketScan. Of these, 35.3% in Medicare and 14.0% in MarketScan had baseline CVD. HR (95% CI) for composite CVD in the overall ABA group versus TNFi was 0.67 (0.55-0.81) in Medicare and 1.08 (0.83-1.41) in MarketScan with the combined HR of 0.79 (0.67-0.92). Among patients with baseline CVD, the HR (95% CI) was 0.71 (0.55-0.92) in Medicare and 1.02 (0.68-1.51) in MarketScan, with the combined HR of 0.79 (0.64-0.98). CONCLUSION: In this large cohort of publicly or privately insured patients with RA in the United States, ABA was associated with a 20% reduced risk of CVD versus TNFi. While this observational study is subject to potential residual confounding, our results were consistent in patients with baseline CVD.
29269418 Biomarker-related risk for myocardial infarction and serious infections in patients with r 2018 Mar BACKGROUND: Rheumatoid arthritis (RA) disease activity and associated systemic inflammation has been associated with serious infection (SIEs), myocardial infarction (MI) and coronary heart disease (CHD) events based on a few registry studies or clinical trials. There are few data from large-scale population-based studies given feasibility challenges in conducting such investigations. METHODS: Multibiomarker disease activity (MBDA) test scores (n=77 641) were linked to Medicare for US patients with RA. Outcomes of interest were hospitalised pneumonia/sepsis (SIE), MI and a composite CHD outcome. The MBDA score ranges from 1 to 100 and was analysed as time-varying. Cox proportional hazards models evaluated the association between MBDA score and SIEs, MI and CHD events, controlling for potential confounders. A sensitivity analysis excluded C reactive protein (CRP) from the MBDA score. RESULTS: There were 17 433 and 16 796 patients eligible for the SIE and MI/CHD analyses, respectively. Mean (SD) age was 69 (11) years, 79% were women, 81% were white and 38% were disabled. Over 16 424 person-years of follow-up, there were 452 SIE events, 132 MIs and 181 CHD events. Higher MBDA scores were associated with SIEs (HR=1.32, 95% CI 1.23 to 1.41 per 10 unit MBDA score change). For MI/CHD events, a threshold effect was present; higher disease activity by MBDA score was associated with increased MI (HR=1.52, 95% CI 0.92 to 2.49) and CHD rates (HR=1.54, 95% CI 1.01 to 2.34, comparing scores ≥30 vs <30). Analyses of the MBDA score without CRP yielded similar results. CONCLUSION: Higher MBDA scores were associated with hospitalised infection, MI and CHD events in a large, predominantly older, US RA population.
30141013 Generation of Recombinant Monoclonal Antibodies from Single B Cells Isolated from Synovial 2018 Ectopic lymphoid structure (ELS) can form in the target tissues of patients with chronic inflammatory autoimmune diseases such as rheumatoid arthritis (RA) and Sjögren's syndrome (SS). Although it is still not clear why ELS form only in a subset of patients, it is well known that these structures can acquire features of ectopic germinal centers and contribute actively to the production of autoantibodies. Here, we describe a method to generate recombinant monoclonal antibodies from single ELS(+) synovial tissue B cells obtained from RA patients. This chapter gives a detailed description of the method beginning from the mononuclear cell preparation from RA synovial tissue, single-cell sort of B cells by flow cytometry, amplification of the immunoglobulin (Ig) genes (both heavy- and light-chain genes) by PCR, and subsequent Ig gene expression vector cloning for full recombinant IgG1 monoclonal antibody (rmAb) production in vitro. The recombinant mAbs generated can be then characterized for (1) analysis of the Ig gene repertoires for clonal studies, (2) immunoreactivity profile, and (3) functional studies both in vitro and in vivo.
30233578 Inhibition of Glycolysis Reduces Disease Severity in an Autoimmune Model of Rheumatoid Art 2018 The K/BxN mouse is a spontaneous model of arthritis driven by T cell receptor transgenic CD4(+) T cells from the KRN strain that are activated by glucose-6-phosphate isomerase (GPI) peptides presented by the H-2(g7) allele from the NOD strain. It is a model of autoimmune seropositive arthritis because the production of anti-GPI IgG is necessary and sufficient for joint pathology. The production of high levels of anti-GPI IgG requires on the expansion of CD4(+) follicular helper T (Tfh) cells. The metabolic requirements of this expansion have never been characterized. Based on the therapeutic effects of the combination of metformin and 2-deoxyglucose (2DG) in lupus models that normalized the expansion of effector CD4(+) T cells. We showed that the CD4(+) T cells and to a lesser extent, the B cells from K/BxN mice are more metabolically active than the KRN controls. Accordingly, preventive inhibition of glycolysis with 2DG significantly reduced joint inflammation and the activation of both adaptive and innate immune cells, as well as the production of pathogenic autoantibodies. However, contrary to the lupus-prone mice, the addition of metformin had little beneficial effect, suggesting that glycolysis is the major driver of immune activation in this model. We propose that K/BxN mice are another model in which autoreactive Tfh cells are highly glycolytic and that their function can be limited by inhibiting glucose metabolism.
31203926 Rheumatoid arthritis and thyroid dysfunction: A cross-sectional study and a review of the 2018 Oct Thyroid dysfunction appears to show increased prevalence in many autoimmune diseases; however, this comorbidity has not been properly investigated in patients with RA. This issue was addressed in this cross-sectional study. Using the database of the Clalit Health Services (CHS) in Israel, RA patients were paired with age- and sex-matched controls to compare the prevalence of hypothyroidism and hyperthyroidism. Chi-squared and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study included 11,782 patients with RA and 57,973 controls. The rate of thyroid dysfunction diseases in RA patients was increased compared with the prevalence in controls (16.0% and 11.7%, p < 0.001, for hypothyroidism; and 2.33% and 1.81%, p < 0.001 in hyperthyroidism, respectively). In a multivariate analysis, RA was associated with hypothyroidism (OR = 1.42, 95% CI 1.34-1.50) and hyperthyroidism (OR = 1.26, 95% CI 1.10-1.45). RA is associated with thyroid dysfunction. Therefore, physicians treating patients with RA should be aware of the possibility of comorbid thyroid dysfunction and treat accordingly.
28079986 Establishment of an in vitro three-dimensional model for cartilage damage in rheumatoid ar 2018 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to progressive joint destruction. To further understand the process of rheumatoid cartilage damage, an in vitro model consisting of an interactive tri-culture of synovial fibroblasts (SFs), LPS-stimulated macrophages and a primary chondrocyte-based tissue-engineered construct was established. The tissue-engineered construct has a composition similar to that of human cartilage, which is rich in collagen type II and proteoglycans. Data generated from this model revealed that healthy chondrocytes were activated in the presence of SFs and macrophages. The activated chondrocytes subsequently displayed aberrant behaviours as seen in a disease state such as increased apoptosis, decreased gene expression for matrix components such as type II collagen and aggrecan, increased gene expression for tissue-degrading enzymes (MMP-1, -3, -13 and ADAMTS-4, -5), and upregulation of inflammatory mediator gene expression (TNF-α, IL-1β, IL-6 and IKBKB). Additionally, the inclusion of SFs and macrophages in the model enabled both cell types to more closely replicate an in vivo role in mediating cartilage destruction. This is evidenced by extensive matrix loss, detected in the model through immunostaining and biochemical analysis. Subsequent drug treatment with celecoxib has shown that the model was able to respond to the therapeutic effects of this drug by reversing cartilage damage. This study showed that the model was able to recapitulate certain pathological features of an RA cartilage. If properly validated, this model potentially can be used for screening new therapeutic drugs and strategies, thereby contributing to the improvement of anti-rheumatic treatment. Copyright © 2017 John Wiley & Sons, Ltd.
29996869 Planning a future randomized clinical trial based on a network of relevant past trials. 2018 Jul 11 BACKGROUND: The important role of network meta-analysis of randomized clinical trials in health technology assessment and guideline development is increasingly recognized. This approach has the potential to obtain conclusive results earlier than with new standalone trials or conventional, pairwise meta-analyses. METHODS: Network meta-analyses can also be used to plan future trials. We introduce a four-step framework that aims to identify the optimal design for a new trial that will update the existing evidence while minimizing the required sample size. The new trial designed within this framework does not need to include all competing interventions and comparisons of interest and can contribute direct and indirect evidence to the updated network meta-analysis. We present the method by virtually planning a new trial to compare biologics in rheumatoid arthritis and a new trial to compare two drugs for relapsing-remitting multiple sclerosis. RESULTS: A trial design based on updating the evidence from a network meta-analysis of relevant previous trials may require a considerably smaller sample size to reach the same conclusion compared with a trial designed and analyzed in isolation. Challenges of the approach include the complexity of the methodology and the need for a coherent network meta-analysis of previous trials with little heterogeneity. CONCLUSIONS: When used judiciously, conditional trial design could significantly reduce the required resources for a new study and prevent experimentation with an unnecessarily large number of participants.
29947235 miRNA-31 over-expression improve synovial cells apoptosis induced by RA. 2018 OBJECTIVE: The aim of this study was to evaluate the effects and mechanism of miRNA-31 in synovial cells apoptosis induced by RA. METHODS: The miRNA-31 gene expressions were extracted from synovial tissues of normal and RA patients by RT-PCR and H et E staining. The synovial cells of RA patients were isolated and randomly divided into Control, Blank and miRNA groups. The cell apoptosis of difference groups were measured by flow cytometry; the TNF-α and IL-1β concentrations of difference groups were measured by Elisa assay; TLR4 and NF-κB proteins expressions were measured by WB assay and the correlation between TLR4 and miRNA-31 were evaluated by double luciferase target experiment. RESULTS: The miRNA-31 gene expression was significantly suppressed in RA tissues (p<0.001); Compared with control group, the cell apoptosis rate of miRNA group was significantly suppressed (p<0.001); TNF-α and IL-1β concentrations were significantly down-regulation in culture fluid (p<0.001, respectively) and TLR4 and NF-κB proteins expressions were significantly depressed (p<0.001, respectively) in miRNA group. By double luciferase target experiment, the TLR4 was a target gene of miRNA-31. CONCLUSION: miRNA-31 is a key role in synovial cells apoptosis induced by RA (Fig. 7, Ref. 23).
29209792 The impact of smoking on disease measures in rheumatoid arthritis: the need for appropriat 2018 Feb In a recent publication, Quintana-Dunque et al. studied patients with early onset rheumatoid arthritis (RA) and showed that baseline smoking status was inversely associated with disease activity and disability at 36 months. The authors conclude that smoking may not be as deleterious as previously considered in RA disease course. However, the authors fail to highlight several limitations of study design and analysis, including time-varying confounding, which may have a direct impact on results and corresponding conclusions.
27178205 Arthritis, Depression, and Falls Among Community-Dwelling Older Adults: Evidence From the 2018 Sep The aims of this study were to examine the association between different types of arthritis and falls and to investigate whether clinically significant depression symptoms (CSDS) moderate these relationships. The study used nationally representative data from the 2008 Health and Retirement Study ( n = 7,715, M age = 75, 62% female, and 90% White). Among the respondents, 42% experienced at least one fall during the previous 2 years. About one third had some form of arthritis: 22% osteoarthritis (OA), 4.8% rheumatoid arthritis (RA), 2.3% both OA and RA, and 7.9% with other arthritis types. About one fifth of respondents had CSDS. OA and CSDS are associated with the odds of falling (17% and 29%, respectively), adjusting for socio-demographic characteristics, lifestyle, health conditions, and psychiatric medications. There was no statistically significant interaction between types of arthritis and CSDS. Health care providers should pay attention to managing arthritis, especially OA, and CSDS to prevent falls among older adults.
29651639 Abatacept for Treatment of Rheumatoid Arthritis: Special Focus on the Elderly. 2018 May Targeted therapies have been developed for patients with rheumatoid arthritis (RA) for whom prior treatment with traditional disease-modifying anti-rheumatic drugs has failed. The numerous different signaling pathways now targeted by various classes of monoclonal antibodies and small molecule inhibitors may complicate treatment decisions. Abatacept selectively modulates a co-stimulatory signal necessary for T-cell activation. Thus, abatacept is effective in biologic-naive patients and in those for whom biologic therapy has failed. Emerging evidence indicates different benefits depending on patient and disease characteristics. In RA, the clinical goal should be clinical and radiographic remission to prevent structural damage and functional impairment. Nevertheless, the management of elderly patients with RA is often less aggressive, and the treat-to-target strategy is less respected in this age category than in the treatment of RA in younger patients. However, abatacept treatment in elderly patients is as effective and well-tolerated as in younger patients. This review summarizes recently published data on pharmacological properties; clinical and biological data on efficacy, drug retention, and safety, focusing on age; and evidence-based criteria for choosing abatacept or an alternative targeted therapy.
30097896 Recommendations for the management of rheumatoid arthritis in the Eastern Mediterranean re 2018 Nov Clinical practice guidelines can assist rheumatologists in the proper prescription of newer treatment for rheumatoid arthritis (RA). The objective of this paper is to report on the recommendations for the management of patients with RA in the Eastern Mediterranean region. We adapted the 2015 American College of Rheumatology guidelines in two separate waves. We used the adolopment methodology, and followed the 18 steps of the "Guidelines 2.0" comprehensive checklist for guideline development. For each question, we updated the original guidelines' evidence synthesis, and we developed an Evidence Profile (EP) and an Evidence to Decision (EtD) table. In the first wave, we adoloped eight out of the 15 original questions on early RA. The strength changed for five of these recommendations from strong to conditional, due to one or more of the following factors: cost, impact on health equities, the balance of benefits, and harms and acceptability. In the second wave, we adoloped eight out of the original 44 questions on established RA. The strength changed for two of these recommendations from strong to conditional, in both cases due to cost, impact on health equities, balance of benefits and harms, and acceptability. The panel also developed a good practice recommendation. We successfully adoloped 16 recommendations for the management of early and established RA in the Eastern Mediterranean region. The process proved feasible and sensitive to contextual factors.
28657833 Serum interleukin-6 and survivin levels predict clinical response to etanercept treatment 2018 Jan OBJECTIVES: To investigate the correlation of nine potential biomarkers with clinical response to etanercept (ETN) therapy in establish rheumatoid arthritis (RA) patients. METHODS: Seventy-three patients with established RA were enrolled in the prospective cohort study. Sixty-nine of 73 cases were included into final analysis for response after 24-week ETN therapy. Serum expression of nine studied proteins was measured by enzyme-linked immunosorbent assay (ELISA). Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-17A, IL-21, IL-34, RANKL, survivin, and COMP were selected as candidate biomarkers. RESULTS: Serum IL-6 level was increased in responders than in nonresponders at baseline, p = .034; to the contrary, serum survivin level was decreased in responders, p = .009. Receiver operating characteristic (ROC) curve illuminated the combination of IL-6 and survivin expressions could predict clinical response with a high AUC 0.875, 95% CI: 0.771-0.976. Furthermore, we found the combination of IL-6 high expression and survivin low expression increased the responding possibility to nearly 20-fold (OR 19.687, 95% CI: 4.087-94.839, p < .001) compared to IL-6 low or survivin high expression by univariate analysis. However, only survivin low expression (p = .002) and CRP (p = .014) high expression were independent predictive factors for achieving clinical response, while IL-6 lack independent predictive value (p = .267). CONCLUSIONS: Comprehensive measurement of IL-6 and survivin in serum could be served as a convincing biomarker for clinical response in ETN-treated patients with established RA.