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ID PMID Title PublicationDate abstract
28850019 Lipopolysaccharide-binding protein is a sensitive disease activity biomarker for rheumatoi 2018 Mar OBJECTIVES: This study was performed to evaluate the performance and clinical significance of lipopolysaccharide-binding protein (LBP) as a disease activity biomarker in rheumatoid arthritis (RA). METHODS: LBP levels were measured by enzyme-linked immunosorbent assay (ELISA). The associations between LBP and the clinical and serological features of RA and its clinical significance as a RA disease activity biomarker were analysed. RESULTS: The serum level of LBP in RA was significantly elevated compared to those in OA, SLE, pSS and HC. The level of LBP in RA synovial fluid (SF) was higher than that in OA SF. LBP was significantly correlated with RA disease activity parameters such as ESR, CRP, tender joint counts, swelling joint counts and DAS28. Furthermore, LBP positive RA patients were more likely to show higher disease activity (DAS28>5.1), positive APF, interstitial lung disease and metabolic disorders. The predictive value of LBP on high disease activity was comparable with those of CRP and ESR. In 52.5% of the patients with active disease but negative in CRP /ESR, LBP was still positive and correlated with swelling joint counts. CONCLUSIONS: LBP is a sensitive serum biomarker to evaluate RA disease activity, and it could be a promising laboratory marker to assist RA disease activity assessment in active RA patients with negative ESR or CRP.
29317506 The interplay between citrullination and HLA-DRB1 polymorphism in shaping peptide binding 2018 Mar 2 The HLA-DRB1 locus is strongly associated with rheumatoid arthritis (RA) susceptibility, whereupon citrullinated self-peptides bind to HLA-DR molecules bearing the shared epitope (SE) amino acid motif. However, the differing propensity for citrullinated/non-citrullinated self-peptides to bind given HLA-DR allomorphs remains unclear. Here, we used a fluorescence polarization assay to determine a hierarchy of binding affinities of 34 self-peptides implicated in RA against three HLA-DRB1 allomorphs (HLA-DRB1*04:01/*04:04/*04:05) each possessing the SE motif. For all three HLA-DRB1 allomorphs, we observed a strong correlation between binding affinity and citrullination at P4 of the bound peptide ligand. A differing hierarchy of peptide-binding affinities across the three HLA-DRB1 allomorphs was attributable to the β-chain polymorphisms that resided outside the SE motif and were consistent with sequences of naturally presented peptide ligands. Structural determination of eight HLA-DR4-self-epitope complexes revealed strict conformational convergence of the P4-Cit and surrounding HLA β-chain residues. Polymorphic residues that form part of the P1 and P9 pockets of the HLA-DR molecules provided a structural basis for the preferential binding of the citrullinated self-peptides to the HLA-DR4 allomorphs. Collectively, we provide a molecular basis for the interplay between citrullination of self-antigens and HLA polymorphisms that shape peptide-HLA-DR4 binding affinities in RA.
29193840 Overweight, Obesity, and the Likelihood of Achieving Sustained Remission in Early Rheumato 2018 Aug OBJECTIVE: Obesity is implicated in rheumatoid arthritis (RA) development, severity, outcomes, and treatment response. We estimated the independent effects of overweight and obesity on ability to achieve sustained remission (sREM) in the 3 years following RA diagnosis. METHODS: Data were from the Canadian Early Arthritis Cohort, a multicenter observational trial of early RA patients treated by rheumatologists using guideline-based care. sREM was defined as Disease Activity Score in 28 joints (DAS28) <2.6 for 2 consecutive visits. Patients were stratified by body mass index (BMI) as healthy (18.5-24.9 kg/m(2) ), overweight (25-29.9 kg/m(2) ), and obese (≥30 kg/m(2) ). Cox regression was used to estimate the effect of the BMI category on the probability of achieving sREM over the first 3 years, controlling for age, sex, race, education, RA duration, smoking status, comorbidities, baseline DAS28, Health Assessment Questionnaire disability index, C-reactive protein level, and initial treatment. RESULTS: Of 982 patients, 315 (32%) had a healthy BMI, 343 (35%) were overweight, and 324 (33%) were obese; 355 (36%) achieved sREM within 3 years. Initial treatment did not differ by BMI category. Compared to healthy BMI, overweight patients (hazard ratio [HR] 0.75 [95% confidence interval (95% CI) 0.58-0.98]) and obese patients (HR 0.53 [95% CI 0.39-0.71]) were significantly less likely to achieve sREM. CONCLUSION: Rates of overweight and obesity were high (69%) in this early RA cohort. Overweight patients were 25% less likely, and obese patients were 47% less likely, to achieve sREM in the first 3 years, despite similar initial disease-modifying antirheumatic drug treatment and subsequent biologic use. This is the largest study demonstrating the negative impact of excess weight on RA disease activity and supports a call to action to better identify and address this risk in RA patients.
30114630 IL-9 receptor: Regulatory role on FLS and pannus formation. 2018 Nov OBJECTIVE: Functions of the Th9 cells and its signature cytokine IL-9 in human autoimmune diseases is currently under extensive research. Here we are reporting new functions of IL-9-receptor (IL-9R); its regulatory role on (i) FLS (fibroblast like synoviocyte) biology and (ii) pannus formation in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: RA, PsA, and OA synovial tissue biopsies were obtained; FLS were derived and cultured from these tissues. T quantify protein and messenger RNA levels of IL9-receptor (IL-9R) Western blot and real-time PCR techniques were used. For Pro-growth/survival effect of IL-9 (rIL-9) Annexin-V (apoptosis assay) and MTT assays were used. RESULTS: Immunoblot and RT-PCR studies demonstrated IL9-R in FLS of RA, PsA, and OA. IL9-R was functionally active. rIL-9 induced significant proliferation of FLS (p < 0.001) and had an inhibitory effect on TNF-α induced apoptosis. Proliferation of FLS induced by rIL-9 could be significantly inhibited (p < 0.001) with an IL-9R antibody. Further we observed, rIL-9 induced increased secretion of IL-6, IL-8 and also unregulated MMP-3 expression in FLS. CONCLUSIONS: Proliferation of FLS, induction of pro-nflammatory cytokines and upregulation of metaloprotinase (MMP 3) the key pathologic events for pannus formation are regulated by IL-9 and its recptor. Thus the IL-9/IL-9R system is a new contributing factor in the cytokine network of PsA and RA.
29606664 Rheumatoid Arthritis Magnetic Resonance Imaging Score Predicts Therapy Response: Results o 2018 Jun OBJECTIVE: Markers for treatment response in rheumatoid arthritis (RA) are lacking. The aim of the study was to assess the performance of the RA magnetic resonance imaging (MRI) scoring system (RAMRIS) in combination with serum biomarkers to predict response to methotrexate (MTX) treatment in therapy-naive patients with early RA by using high-field MRI. METHODS: Twenty-eight patients with RA were prospectively assessed with baseline 3-T MRI of the clinical dominant hand, 3 and 6 months after MTX. The patients met the 2010 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria [average age 56.8 yrs (range 39-74); positive for rheumatoid factor and/or anticyclic citrullinated peptide antibodies; disease duration < 6 mos (range 2-23 weeks)]. RAMRIS and serum biomarkers consisting of various experimental proteins including receptor activator of nuclear factor-κB ligand (RANKL) were obtained. Remission or treatment response was defined according to EULAR. To adjust for intrapersonal correlation, generalized linear mixed models were used. RESULTS: Treatment response at 3 months was associated to low RAMRIS erosion subscores and low total RAMRIS scores (p = 0.019 and 0.03, respectively). Remission at 6 months was associated to low RANKL levels (p = 0.033). In multivariate analyses, response at 3 and 6 months was predicted more accurately with the inclusion of total RAMRIS score, RAMRIS synovitis subscore at the second metacarpophalangeal (MCP) joint, or a combination of the two (p value likelihood ratio test = 0.035, 0.035, and 0.041, respectively). Remission was more accurately predicted with inclusion of RANKL, with no significant predictive effect of MRI. CONCLUSION: Baseline total RAMRIS can predict EULAR response. RAMRIS synovitis subscore at the second MCP joint and RANKL are associated with response and remission, respectively.
29303702 Comparison of the risks of hospitalisation for cardiovascular events in patients with rheu 2018 Mar OBJECTIVES: To verify if tocilizumab (TCZ) is associated with an increased risk of cardiovascular (CV) events compared with etanercept (ETN) in rheumatoid arthritis (RA). METHODS: This is a retrospective cohort study on administrative healthcare databases (AHD) in Italy. Patients were identified using a validated algorithm based on AHD. Exposure to specific drugs was estimated by the drug prescription recorded in the AHD. The occurrence of acute CV events (myocardial infarction, stroke, other CV events) was derived from the hospital discharge forms. The association between TCZ or ETN and CV events was estimated using competing risk models, adjusting for pre-specified confounders. RESULTS: We identified 1,752 subjects with RA, 1,086 treated with ETN and 666 with TCZ. TCZ did not increase the overall risk of acute CV events, even when adjusted for pre-specified confounders (hazard ratio HR 0.95, 95% confidence interval 95%CI 0.54-1.66), specifically of acute myocardial infarction (HR 0.39, 95%CI 0.15-1.06), stroke (HR 1.44, 95%CI 0.24-8.68) or other CV event (1.07, 95%CI 0.59-1.92). CONCLUSIONS: RA patients with TCZ do not have a medium-term excess of CV risk in patients compared with ETN.
29464523 Methotrexate preferentially affects Tc1 and Tc17 subset of CD8 T lymphocytes. 2019 Jan Rheumatoid arthritis is considered a T-lymphocyte-mediated disease. However, studies have focussed on CD4 T-lymphocytes, ignoring CD8 T-lymphocytes despite the latter being found abundantly in the synovium. Specifically, there is little data of the effect of methotrexate, the gold-standard DMARD, on various CD8 cytokine T-lymphocyte subsets and conflicting data on CD4 subsets. In this prospective study, patients with active rheumatoid arthritis, who were 18 to 65 years of age, were treated with methotrexate (up to 25 mg per week) for 24 weeks. At baseline and 24 weeks, frequencies of CD8(+)IFNγ(+), CD8(+)IL17(+), CD8(+)IL4(+), corresponding CD4 subsets and plasma levels of IFNγ, IL-12, IL-10, IL-4 and IL-17 were determined by flow cytometry. These are summarised as median (IQR = interquartile range, 25th-75th percentile) and paired data compared using Wilcoxon signed rank test. This study included 67 patients (F/M = 4:1) with rheumatoid arthritis, 57 (85%) being RF positive and 20 receiving prednisolone at baseline. Mean (± SD) dose of methotrexate at 24 weeks was 22.9 ± 3.0 mg per week. On treatment with methotrexate, there was a significant (p = 0.04) decline in CD8(+)IFNγ(+) cells from 37.2 (IQR 19.4-60.2) to 22.7% (IQR 8.5-49.7) and a marginal increase in CD8(+)IL17(+) cells from 0.3 (IQR 0.1-0.6) to 0.4 (IQR 0.2-1.2), p = 0.006. There was no significant change in the other subsets. There was also a significant decline in circulating levels of IL-12, IL-10 and IL-17 and marginal increase in IL-4. On evaluating by response, non-responders but not responders had a significant increase in CD8(+)IL17(+) (p = 0.01). There is a significant decline of CD8(+)IFNγ(+) T cells and marginal increase in CD8(+)IL17(+) T cells after methotrexate. Change in Tc1 subset may be mediated through reduction in IL-12 levels.
30504507 Smoking Is Associated with Higher Disease Activity in Rheumatoid Arthritis: A Longitudinal 2019 Apr OBJECTIVE: Prior studies around the relationship between smoking and rheumatoid arthritis (RA) disease activity have reported inconsistent findings, which may be ascribed to heterogeneous study designs or biases in statistical analyses. We examined the association between smoking and RA outcomes using statistical methods that account for time-varying confounding and loss to followup. METHODS: We included 282 individuals with an RA diagnosis using electronic health record data collected at a public hospital between 2013 and 2017. Current smoking status and disease activity were assessed at each visit; covariates included sex, race/ethnicity, age, obesity, and medication use. We used longitudinal targeted maximum likelihood estimation to estimate the causal effect of smoking on disease activity measures at 27 months, and compared results to conventional longitudinal methods. RESULTS: Smoking was associated with an increase of 0.64 units in the patient global score compared to nonsmoking (p = 0.01), and with 2.58 more swollen joints (p < 0.001). While smoking was associated with a higher clinical disease activity score (2.11), the difference was not statistically significant (p = 0.22). We found no association between smoking and physician global score, or C-reactive protein levels, and an inverse association between smoking and tender joint count (p = 0.05). Analyses using conventional methods showed a null relationship for all outcomes. CONCLUSION: Smoking is associated with higher levels of disease activity in RA. Causal methods may be useful for investigations of additional exposures on longitudinal outcome measures in rheumatologic disease.
29773705 Vapour, gas, dust and fume occupational exposures in male patients with rheumatoid arthrit 2018 May 17 OBJECTIVES: To quantify exposure to vapour, gas, dust and fumes (VGDF) and smoking in male rheumatoid arthritis (RA) and investigate impact on rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels. DESIGN: A retrospective observational study. SETTING: The Royal Cornwall Hospital Trust, UK. A single university hospital setting. PARTICIPANTS: 726 men followed up between February 2015 and August 2016, fulfilling RA diagnostic criteria. MAIN OUTCOME MEASURES: Prevalence of VGDF exposure and smoking prior to RA diagnosis. Determination of association between VGDF, smoking and autoantibody levels. RESULTS: 546/726 (75%) had been exposed to VGDF for >1 year. 561/726 (77%) had been smokers. Only 58/726 (8%) had no exposure to VGDF and had never smoked. A significant difference in RF levels was observed between unexposed and VGDF exposed never smokers (median RF 24 vs 36, p=0.03), more marked when comparing unexposed with ≥2 VGDF exposures (median RF 24 vs 57, p=0.02). A significant difference in RF levels was also observed between unexposed and VGDF exposed smokers (median RF 71 vs RF 95, p=0.04), more marked when comparing unexposed with ≥2 VGDF exposures (median RF 71 vs RF 113, p=0.01). A significant difference in RF titre was observed between never smokers >2 VGDF exposures and smokers with >2 VGDF exposures (RF 57 vs RF 113, p=0.02). No association of ACPA seropositivity rates or titres with VGDF exposure was observed. Smokers with >2 VGDF exposures had a significantly lower age of RA diagnosis than smokers with no VGDF exposure (53 years vs 57 years, p=0.03). All results remained similar when corrected for social class. CONCLUSIONS: VGDF exposure increases RF levels. Combination exposure to smoking and VDGF results in higher RF levels, particularly with multiple exposures. These compelling findings demonstrate the importance of combined inhaled exposures in RF generation.
30160157 Evaluation of pancreatic exocrine functions in rheumatoid arthritis. 2018 BACKGROUND: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory diseases. It mainly involves the joints and also affects directly or indirectly nearly all organ systems. The question whether RA causes exocrine pancreatic disfunction remains unclear. The purpose of this study is to evaluate whether or not RA contributes to pancreatic exocrine insufficiency. This was done by ruling out seconder Sjögren's syndrome (SjS) by using Schirmer's test. METHODS: A total of 60 patients (20 RA, 20 RA + SjS and 20 SjS) and 20 healthy volunteers were included in the study. Patients with RA who had not undergonethe Schirmer's test in the last 6 months and all healthy volunteers included in the study underwent the Schirmer's test at an outpatient clinic. Random fecal samples were taken from all participants and fecal pancreatic elastase was measured to evaluate pancreatic exocrine functions. RESULTS: In the study, a statistically significant difference was found between the control group,SjS and RA+SjS groups. But there was no significant difference between the control group and RA group. In RA group, fecal elastase levels were statistically significantly higher compared to the SjS group. But there was no significant difference between RA+SjS and SjS groups. CONCLUSION: Fecal elastase significantly decreased in SjS compared to the normal population while pancreatic exocrine functions are considered to be impaired in SjS. There are also impaired pancreatic exocrine functions in the secondary SjS associated with RA. Consequently, pancreatic exocrine dysfunction, which can be seen in patients with RA, may be thought to be caused by secondary SjS associated with RA (Tab. 6, Fig. 1, Ref. 19).
30289537 The influence of comorbidities on the efficacy of tumour necrosis factor inhibitors, and t 2018 Oct 1 OBJECTIVE: To define the safety and efficacy of TNF inhibitors (TNFi) in RA patients with comorbidities. METHODS: A National Consensus Conference adopted a five-step process to better address the place of TNFi in the treatment of RA. Here we report the work focused on the influence of comorbidities on TNFi efficacy and the effect of TNFi on comorbidities using a Population Intervention Comparison Outcome-based strategy from 8 April 2013 to 15 January 2016. RESULTS: A total of 4453 hits were analysed, of which 10 were eligible for full review. Data show that the presence of comorbidities influences the treatment strategy and several clinical outcomes. The risk of solid cancer is similar in RA patients treated with TNFi or with conventional synthetic DMARDs, and the risk of recurrent breast cancer is not higher in RA patients treated with TNFi. The risk of developing serious infections is higher in RA patients receiving TNFi than conventional synthetic DMARDs. Patients with previous serious infections before starting TNFi are not at increased risk of subsequent serious infection. The hazard rate of hospitalization due to infections is not different among patients remaining on the same TNFi, or switching to a different TNFi or to an agent with another mechanism of action. Longer exposure to TNFi is associated with a reduction in the risk of cardiovascular events. CONCLUSION: Comorbidities affect RA treatment strategies and the efficacy of TNFi. TNFi treatment may decrease the risk of cardiovascular diseases and their use in patients with previous infection is not associated with a higher risk of recurrences.
29898765 Ten weeks of high-intensity interval walk training is associated with reduced disease acti 2018 Jun 14 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which adults have significant joint issues leading to poor health. Poor health is compounded by many factors, including exercise avoidance and increased risk of opportunistic infection. Exercise training can improve the health of patients with RA and potentially improve immune function; however, information on the effects of high-intensity interval training (HIIT) in RA is limited. We sought to determine whether 10 weeks of a walking-based HIIT program would be associated with health improvements as measured by disease activity and aerobic fitness. Further, we assessed whether HIIT was associated with improved immune function, specifically antimicrobial/bacterial functions of neutrophils and monocytes. METHODS: Twelve physically inactive adults aged 64 ± 7 years with either seropositive or radiographically proven (bone erosions) RA completed 10 weeks of high-intensity interval walking. Training consisted of 3 × 30-minute sessions/week of ten ≥ 60-second intervals of high intensity (80-90% VO(2reserve)) separated by similar bouts of lower-intensity intervals (50-60% VO(2reserve)). Pre- and postintervention assessments included aerobic and physical function; disease activity as measured by Disease Activity score in 28 joints (DAS28), self-perceived health, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR); plasma interleukin (IL)-1β, IL-6, chemokine (C-X-C motif) ligand (CXCL)-8, IL-10, and tumor necrosis factor (TNF)-α concentrations; and neutrophil and monocyte phenotypes and functions. RESULTS: Despite minimal body composition change, cardiorespiratory fitness increased by 9% (change in both relative and absolute aerobic capacity; p < 0.001), and resting blood pressure and heart rate were both reduced (both p < 0.05). Postintervention disease activity was reduced by 38% (DAS28; p = 0.001) with significant reductions in ESR and swollen joints as well as improved self-perceived health. Neutrophil migration toward CXCL-8 (p = 0.003), phagocytosis of Escherichia coli (p = 0.03), and ROS production (p < 0.001) all increased following training. The frequency of cluster of differentiation 14-positive (CD14(+))/CD16(+) monocytes was reduced (p = 0.002), with both nonclassical (CD14(dim)/CD16(bright)) and intermediate (CD14(bright)/CD16(positive)) monocytes being reduced (both p < 0.05). Following training, the cell surface expression of intermediate monocyte Toll-like receptor 2 (TLR2), TLR4, and HLA-DR was reduced (all p < 0.05), and monocyte phagocytosis of E. coli increased (p = 0.02). No changes were observed for inflammatory markers IL-1β, IL-6, CXCL-8, IL-10, CRP, or TNF-α. CONCLUSIONS: We report for the first time, to our knowledge, that a high-intensity interval walking protocol in older adults with stable RA is associated with reduced disease activity, improved cardiovascular fitness, and improved innate immune functions, indicative of reduced infection risk and inflammatory potential. Importantly, the exercise program was well tolerated by these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02528344 . Registered on 19 August 2015.
29575671 Rituximab May Cause Increased Hepatitis C Virus Viremia in Rheumatoid Arthritis Patients T 2018 Aug OBJECTIVE: Several studies have shown that rituximab may enhance hepatitis C virus (HCV) activity. MicroRNAs (miRNAs) have been implicated in modulating the host immune response in HCV infection; miRNAs can be packaged into the exosomes and then shuttled by the exosomes to aid biologic functions. However, the role of exosomal miRNAs (exo-miRNAs) in rituximab-related HCV activity enhancement remains unclear. METHODS: The association between rituximab and increased HCV activity was examined using an in vitro cell-based assay. Purified exosomes were confirmed using immunoblotting and flow cytometry and quantified using enzyme-linked immunosorbent assay. Exosomal miRNA-155 (exo-miR-155) levels were measured using quantitative reverse transcription-polymerase chain reaction. RESULTS: In vitro data showed that B cell-derived miR-155 could inhibit HCV replication in hepatocytes through exosome transmission. Rituximab could both induce B cell depletion and affect intracellular miR-155 production as well as exo-miR-155 transmission and then enhance HCV activity in hepatocytes (P < 0.005). Serum exosome levels were increased in rheumatoid arthritis (RA) patients with HCV infection compared with the levels in RA patients without HCV infection (P < 0.01). The exo-miR-155 levels were significantly increased in RA patients with HCV infection compared with those without infection (P < 0.01). A significantly greater decrement of exo-miR-155 expression was observed after rituximab therapy compared with those observed before therapy (P < 0.01), and hepatitis C viral loads increased simultaneously (P < 0.05). CONCLUSION: Circulating exo-miR-155 levels were negatively correlated with hepatitis C viral loads and subsequently associated with rituximab-related HCV activity enhancement in RA patients. Exo-miR-155 may become a potential diagnostic biomarker or therapeutic target.
30275258 Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis 2019 Feb OBJECTIVE: Cardiovascular (CV) risk estimation calculators for the general population do not perform well in patients with rheumatoid arthritis (RA). An RA-specific risk calculator has been developed, but did not perform better than a risk calculator for the general population when validated in a heterogeneous multinational cohort. METHODS: In a cohort of patients with new-onset RA from northern Sweden (n = 665), the risk of CV disease was estimated by the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA) and the American College of Cardiology/American Heart Association algorithm (ACC/AHA). The ACC/AHA estimation was analyzed, both as crude data and when adjusted according to the recommendations by the European League Against Rheumatism (ACC/AHA × 1.5). ERS-RA was calculated using 2 variants: 1 from patient and physician reports of hypertension (HTN) and hyperlipidemia [ERS-RA (reported)] and 1 from assessments of blood pressure (BP) and blood lipids [ERS-RA (measured)]. The estimations were compared with observed CV events. RESULTS: All variants of risk calculators underestimated the CV risk. Discrimination was good for all risk calculators studied. Performance of all risk calculators was poorer in patients with a high grade of inflammation, whereas ACC/AHA × 1.5 performed best in the high-inflammatory patients. In those patients with an estimated risk of 5-15%, no risk calculator performed well. CONCLUSION: ERS-RA underestimated the risk of a CV event in our cohort of patients, especially when risk estimations were based on patient or physician reports of HTN and hyperlipidemia instead of assessment of BP and blood lipids. The performance of ERS-RA was no better than that of ACC/AHA × 1.5, and neither performed well in high-inflammatory patients.
30075990 Unmet needs in the treatment of rheumatoid arthritis. An observational study and a real-li 2019 Feb OBJECTIVES: To estimate the size of unmet needs in the treatment of early Rheumatoid Arthritis (eRA), using all the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biological DMARDs (bDMARDs) in a long-term observational study. MATERIALS AND METHODS: 538 patients with eRA were evaluated. The 2010 ACR/EULAR classification criteria were used. All patients were csDMARDs and bDMARDs-naive with disease duration less than one year. They were treated according to EULAR and ACR recommendations for RA. All the csDMARDs and bDMARDs were used. Clinical, laboratory findings with the disease activity score-28 and treatment decisions were all recorded as well as adverse drug reactions, reason of therapy termination, disease complications and comorbidities. RESULTS: Methotrexate (58%) and Infliximab (37%) where the first csDMARD and bDMARD choice respectively. During follow-up, 14 patients were lost and 7 developed comorbidities. The final results are referred to 517 patients. Among those, 66% were treated with csDMARDs as monotherapy or in combination therapy with sustained low disease activity (LDA). However, 3.2% from this group neither achieved LDA, nor received bDMARDs, due to comorbidities. On the other hand, 34% were treated with bDMARDs with or without csDMARDs. The majority of them demonstrated sustained LDA. From this group, 17.7% never achieved LDA, despite that they switched and received all bDMARDs. Thus, 20.9% of our patients never achieved LDA. CONCLUSIONS: Using the current recommendations for RA therapy we successfully treated the majority of our patients. However, we found that the size of gap and the unmet needs for treatment is about 20%.
30092814 Mediterranean diet and risk of rheumatoid arthritis: a population-based case-control study 2018 Aug 9 BACKGROUND: The Mediterranean diet has been associated with lower mortality and lower risk of cardiovascular diseases and cancer. Although its components have been analysed in several studies, only one study has specifically investigated the association between Mediterranean diet and risk of rheumatoid arthritis (RA), and reported no association. METHODS: Data on 1721 patients with incident RA (cases) and 3667 controls, matched on age, gender and residential area, from the Swedish epidemiological investigation of RA (EIRA), a population-based case-control study, were analysed using conditional logistic regression. The Mediterranean diet score, ranging from 0 to 9, was calculated from a 124-item food frequency questionnaire. RESULTS: In the EIRA study (median age of participants 53 years), 24.1% of the patients and 28.2% of the controls had high adherence to the Mediterranean diet (a score between 6 and 9). After adjustments for body mass index, educational level, physical activity, use of dietary supplements, energy intake, and smoking, high adherence reduced the odds of developing RA by 21% (OR 0.79; 95% CI 0.65-0.96) as compared to low adherence (a score between 0 and 2). The OR was even lower among men (OR 0.49; 95% CI 0.33-0.73), but no significant association was found among women (OR 0.94; 95% CI 0.74-1.18). An association between high diet score and low risk of RA was observed in rheumatoid factor (RF)-positive (OR 0.69; 95% CI 0.54-0.88), but not RF-negative RA (OR 0.96; 95% CI 0.68-1.34), and in RA characterised by presence of antibodies to citrullinated peptides (ACPA), but not in ACPA-negative RA. CONCLUSIONS: In this large population-based case-control study, the Mediterranean diet score was inversely associated with risk of RA. However, an association was only found among men and only in seropositive RA.
29589156 Effects of non-surgical periodontal therapy on periodontal laboratory and clinical data as 2019 Jan OBJECTIVES: To compare the effect of non-surgical periodontal therapy on clinical and inflammatory parameters in patients with moderate to severe chronic periodontitis (CP) and rheumatoid arthritis (RA) (RA-CP) with that in CP patients without RA. MATERIAL AND METHODS: Eighteen patients with RA-CP and 18 systemically healthy patients with CP were treated with scaling and root planing (SRP) within 24 h. At baseline, and at 3 and 6 months after SRP, clinical periodontal parameters, inflammatory markers, and microorganisms in subgingival biofilm were assessed. In addition, disease activity markers of RA (DAS28, CRP, ESR) and specific antibodies (RF) were monitored in the RA-CP group. RESULTS: In both groups, non-surgical therapy yielded to statistically significant improvements in all investigated clinical periodontal variables; in RA patients, a statistically significant decrease in serum-CRP was seen at 3 months. At all time-points, levels of inflammatory markers in GCF were higher in RA-CP than in CP patients. Counts of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola decreased statistically significantly in CP but not in the RA-CP group. Changes of DAS28 correlated positively with those of P. gingivalis and negatively with the plaque index. CONCLUSIONS: Within their limits, the present data suggest that (a) non-surgical periodontal therapy improves periodontal conditions in CP patients with and without RA and (b) in patients with RA, eradication of P. gingivalis in conjunction with a high level oral hygiene may transiently decrease disease activity of RA. CLINICAL RELEVANCE: In patients with RA and CP, non-surgical periodontal therapy is a relevant modality not only to improve the periodontal condition but also to decrease RA activity.
29848990 Knowledge-Based Neuroendocrine Immunomodulation (NIM) Molecular Network Construction and I 2018 May 30 Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, we first collected a core dataset of NIM signaling molecules based on our knowledge and obtained 611 NIM signaling molecules. Then, we built a NIM molecular network based on the MetaCore database and analyzed the signaling transduction characteristics of the core network. We found that the endocrine system played a pivotal role in the bridge between the nervous and immune systems and the signaling transduction between the three systems was not homogeneous. Finally, employing the forest algorithm, we identified the molecular hub playing an important role in the pathogenesis of rheumatoid arthritis (RA) and Alzheimer's disease (AD), based on the NIM molecular network constructed by us. The results showed that GSK3B, SMARCA4, PSMD7, HNF4A, PGR, RXRA, and ESRRA might be the key molecules for RA, while RARA, STAT3, STAT1, and PSMD14 might be the key molecules for AD. The molecular hub may be a potentially druggable target for these two complex diseases based on the literature. This study suggests that the NIM molecular network in this paper combined with the forest algorithm might provide a useful tool for predicting drug targets and understanding the pathogenesis of diseases. Therefore, the NIM molecular network and the corresponding online tool will not only enhance research on complex diseases and system biology, but also promote the communication of valuable clinical experience between modern medicine and Traditional Chinese Medicine (TCM).
29796624 Effect of cumulative exposure to corticosteroid and DMARD on radiographic progression in r 2018 Sep 1 OBJECTIVES: Several authors have tried to predict the risk of radiographic progression in RA according to baseline characteristics, considering exposure to treatment only as a binary variable (Treated: Yes/No). This study aims to model the risk of 5-year radiographic progression taking into account both baseline characteristics and the cumulative time-varying exposure to corticosteroids or DMARDs. METHODS: The study population consisted of 403 patients of the Etude et Suivi des Polyarthrites Indifférenciées Récentes cohort meeting the 1987 ACR or 2010 ACR/EULAR criteria for RA at inclusion and having complete radiographic data at baseline and 5 years. Radiographic progression was defined at 5 years as a significant increase of the Sharp/van der Heidje score (smallest detectable difference ⩾5). The best logistic regression model was selected from the following: model including only clinico-biological baseline characteristics; model considering baseline characteristics and treatments as binary variables; and model considering baseline characteristics and treatments as weighted cumulative exposure variables. RESULTS: Radiographic progression occurred in 143 (35.5%) patients. The best model combined anti-citrullinated peptide antibody positivity, ESR, swollen joint count >14 and erosion score at baseline, as well as corticosteroids, MTX/LEF (MTX or LEF) and biologic DMARDs (bDMARDs) as weighted cumulative exposure variables. Recent cumulative exposure to high doses of corticosteroids (⩽ 3months) was significantly associated with the risk of 5-year radiographic progression and a significant protective association was highlighted for a 36-month exposure to bDMARDs. CONCLUSION: Corticosteroids and bDMARDs play an important role in radiographic progression. Accounting for treatment class and intensity of exposure is a major concern in predictive models of radiographic progression in RA patients.
29713730 Prostaglandin E2 and IL-23 interconnects STAT3 and RoRγ pathways to initiate Th17 CD4(+) 2018 Jul BACKGROUND: The chronic inflammation associated with rheumatoid arthritis (RA) leads to focal and systemic bone erosion of the joints resulting in a crippling disability. Recent reports indicate an increase in the incidence of RA in the coming years, placing a significant burden on healthcare resources. The incidence of RA is observed to be increasing with age and a significant proportion of those new cases will be aggressively erosive. FINDINGS: The altered physiology, due to immune disturbances, contributes towards RA pathogenesis. The imbalance of inflammatory cytokines and non-cytokine immune modulators such as prostaglandin E2 (PGE2) and IL-23-induced pathogenic IL-17, plays a crucial role in persistent inflammation and bone degradation during RA. However, the molecular mechanism of IL-23, a key cytokine, and PGE2 in the development and perpetuation of IL-17 producing effector Th17 cells is poorly understood. CONCLUSION: This review focuses on research findings that provide insight into the contribution of PGE2 and IL-23 during the development of pathogenic Th17 cells. We also highlight the key transcriptional factors required for Th17 development and therapeutic strategies to disrupt the interaction between IL-23 and IL-17 to prevent the end-organ damage in RA.