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ID PMID Title PublicationDate abstract
30168274 Influence of methotrexate on gastrointestinal symptoms in patients with rheumatoid arthrit 2019 Feb AIM: This study aimed to determine the influence of methotrexate (MTX) on gastrointestinal (GI) symptoms in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study examined 529 consecutive patients with RA receiving oral MTX in our department between April 1 and September 30, 2017. GI symptoms were evaluated by the Gastrointestinal Symptom Rating Scale (GSRS); a score of ≥2 was considered "symptomatic." Prevalence of GI symptoms was compared between patients receiving ≤8 mg/wk (low-dose) vs >8 mg/wk (high-dose) of MTX. RESULTS: Of our study population, 313 (59%) received low-dose MTX at a median (interquartile range) dose of 6 (6-8) mg/wk, whereas 216 (41%) received high-dose MTX at a median dose of 12 (10-12) mg/wk. Relative to the low-dose MTX group, the high-dose MTX group exhibited a higher prevalence of reflux (32% vs 24%, P = 0.043) and abdominal pain (28% vs 18%, P = 0.007). There was no significant group-dependent difference in the prevalence of indigestion, diarrhea or constipation. Multivariate logistic regression analysis revealed that high-dose MTX (>8 mg/wk) was independently associated with reflux (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.07-2.43) and abdominal pain (OR: 1.60, 95% CI: 1.04-2.43), and that the ORs for reflux and abdominal pain among those receiving high-dose MTX (>8 mg/wk) were similar to those using nonsteroidal anti-inflammatory drugs. CONCLUSION: High-dose MTX is independently associated with the prevalence of upper GI symptoms in Japanese patients with RA.
31165251 [ADAPTHERA-Statewide cross-sectoral care network for patients with early rheumatoid arthri 2019 Sep BACKGROUND/OBJECTIVE: The majority of patients in Germany miss out on the necessity of early diagnosis and initiation of therapy for rheumatoid arthritis (RA) caused by considerable structural deficits in the health care system. The challenge is to reconcile the individual demand for the best possible therapy result with a sustainable expenditure of resources. METHODS: The cross-sectoral regional care network ADAPTHERA aims to improve early RA diagnosis and treatment in Rhineland-Palatinate. The retrospective triage analyses of suspected early onset RA patients was performed by tracing the selection process of all available enquiries (n = 1045). For analysis of the clinical course of the disease, a subset comprising 143 patients with a minimum observation time of 12 months (5 consecutive visits) was available. Clinical and laboratory parameters were collected quarter yearly, self-administered questionnaires were filled out and the treatment was adapted if necessary. RESULTS: A total of 454 patients were included. The mean waiting time was 23.9 (SD = 18) days. The mean observation period in the subcohort was 29.2 (SD = 12.7) months, with about 50% of the patients presenting within 3 months. Almost 75% of the patients were in remission after 2 years. A sustained remission could be described for 74.8% (6 months) and 53.5% (12 months), respectively. Especially patients with rapid remission induction benefited in terms of longer remissions (p = 0.03). A very early stage of the disease (VERA) was associated with a rarely necessary biologic therapy (p = 0.022). DISCUSSION: The approach of a supply network is not a panacea, but it might improve healthcare for patients with early onset RA. In order to minimize resource utilization, a pinpoint referral and accurate triage of potential cases are crucial.
31141478 Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next bi 2019 Oct 25 Background Previous reviews of the diagnosis for rheumatoid arthritis (RA) have not compared anti-mutated citrullinated vimentin (MCV) with anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) in respect of sensitivity, specificity and the area under the curve (AUC) against disease controls for differential diagnosis. This meta-analysis aims to evaluate the value of anti-MCV in the diagnosis for RA, the combined sensitivity of anti-MCV and anti-CCP, and certain clinical characteristics related to the performance of anti-MCV. Methods Medline, Embase, Cochrane Library and Web of Science were searched for articles published up to 25 August 2018. A total of 33 studies including 6044 RA patients and 5094 healthy or disease controls achieved inclusive criteria. QUADAS-2 was applied to evaluate the quality of the included studies. The bivariate random effects model was employed in primary data synthesis to evaluate the diagnostic performance. Results The sensitivity of anti-MCV, anti-CCP and RF in RA diagnosis against a disease control group was 0.71, 0.71, 0.77, with the specificity of 0.89, 0.95, 0.73, and the AUC of the SROC of 0.89, 0.95, 0.82, respectively. The predesign of the primary study and diagnostic criteria were statistically significant as sources of heterogeneity. Anti-MCV and anti-CCP tests demonstrated a sensitivity of 0.77 when performed in parallel, with a sensitivity of 0.60 when performed in series; whereas, the combination of anti-MCV and RF presented a sensitivity of 0.64 when used in series. Conclusions Anti-MCV demonstrates comparable diagnostic value to anti-CCP and RF, thus it can be an effective diagnostic marker for RA and may be written into the next authoritative criteria.
28750190 Design and Characterization of a Soft Robotic Therapeutic Glove for Rheumatoid Arthritis. 2019 The modeling and experimentation of a pneumatic actuation system for the development of a soft robotic therapeutic glove is proposed in this article for the prevention of finger deformities in rheumatoid arthritis (RA) patients. The Rehabilitative Arthritis Glove (RA-Glove) is a soft robotic glove fitted with two internal inflatable actuators for lateral compression and massage of the fingers and their joints. Two mechanical models to predict the indentation and bending characteristics of the inflatable actuators based on their geometrical parameters will be presented and validated with experimental results. Experimental validation shows that the model was within a standard deviation of the experimental mean for input pressure range of 0 to 2 bars. Evaluation of the RA-Glove was also performed on six healthy human subjects. The stress distribution along the fingers of the subjects using the RA-Glove was also shown to be even and specific to the finger sizes. This article demonstrates the modeling of soft pneumatic actuators and highlights the potential of the RA-Glove as a therapeutic device for the prevention of arthritic deformities of the fingers.
31366819 Serum Soluble Interleukin-2 Receptor Is a Biomarker for Pneumocystis jirovecii Pneumonia a 2019 Jul Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.
30747775 The Association Between Yoga Use, Physical Function, and Employment in Adults With Rheumat 2019 Mar/Apr Mind-body exercises such as yoga offer patients with rheumatoid arthritis (RA) a symptom management strategy for improving physical and mental health. Studies have evaluated yoga to manage symptoms of RA and improve physical function; however, none has examined the relationship between yoga and work status in adults with RA. The objective was to describe differences in RA symptomatology, physical function scores, and work status between adults with RA who participate in yoga and those who do not. This cross-sectional study surveyed adults with rheumatologist-diagnosed RA regarding yoga use in the past year, symptoms, physical function, and work status. Differences between yoga and non-yoga participation groups were assessed with 2-sided t tests or Pearson χ tests. Multivariate linear regression analyses were conducted to identify significant associations between yoga participation and primary outcomes. The sample included 398 adults with RA; 88% were females, 66% were white, mean age 61.8 years, mean disease duration 24.8 years; 10.6% participated in yoga. Vinyasa, Bikram, Hatha, Iyengar, and restorative yoga styles were practiced, mostly in a group setting. Yoga participants were significantly more likely to work full-time, less likely to be unable to work due to disability, and had better physical function. These findings characterize yoga practice and practitioners among adults with RA. In adults with RA, yoga participation is associated with full-time work status and better physical function than nonparticipation. This study adds additional information to the growing body of literature about adults with RA who practice yoga.
29965853 Validity of 7-Joint Versus Simplified 12-Joint Ultrasonography Scoring Systems in Assessme 2019 Sep INTRODUCTION: Musculoskeletal ultrasonography (US) is an objective tool for the evaluation of disease activity in rheumatoid arthritis (RA) patients. There is no consensus on the exact number of joints that should be examined. Examination of reduced joint count is more practical than the comprehensive one. OBJECTIVES: This is a cross-sectional study investigated the validity of a 7-joint US score (US7) in assessment of joint inflammation in RA patients compared with a simplified 12-joint US score (US12) and correlated both to composite disease activity indices. METHODS: The activity status of 50 RA patients was assessed clinically and ultrasonographically. The disease activity was calculated using 3 composite indices. Ultrasonography was performed by 1 blinded rheumatologist, using power Doppler (PD) and gray-scale (GS) US examination. The US7 and simplified US12 were performed as originally described. However, the GS synovitis and PD synovitis of US12 were computed in 2 separate scores instead of 1. Two sum US7 scores were added, sum (GS) US7 and sum (PD) US7 after summating synovitis and tenosynovitis scores. Ultrasonography interobserver/intraobserver reliability was evaluated on 40 stored images. RESULTS: Correlation coefficient between the different ultrasonographic scores showed no difference. The GS scores showed no correlation with disease activity parameters; however, the PD scores did. The sum (PD) US7 was the only score that showed significant correlation with the 3 different composite disease indices. CONCLUSIONS: All studied US scores proved valid in assessment of disease activity status in RA. This is in favor of using the less-time-consuming US7 scores. The strongest correlation found with sum (PD) US7 confirmed the importance of incorporating the tendon in the disease activity assessment.
31246497 Overexpression of miR-101 May Target DUSP1 to Promote the Cartilage Degradation in Rheumat 2019 Oct This study aimed to explore crucial genes that contribute to the development of rheumatoid arthritis (RA). Three GSE77298, GSE55457, and GSE55235 data sets were used to analyze the differentially expressed genes (DEGs) between RA synovial membrane tissue samples and normal synovial membrane tissue samples. Then, the functional enrichment analysis and protein-protein interactions (PPIs) construction were performed for DEGs. Subsequently, submodule analysis and regulatory network that contained transcription factors (TFs), microRNAs, and their targets were conducted. Finally, small-molecule drugs related to the DEGs were predicted. A total of 173 upregulated and 54 downregulated DEGs identified in at least 2 of 3 data sets. TYROBP, CTSS, MMP9, CXCR4, and CXCL10 were both highlighted in the PPI and submodule networks. In addition, miR-101, IRF1 TF, DUSP1, and CXCR4 had high degree in the regulatory network, and regulation pairs of miR-101-DUSP1 and IRF1 TF-CXCR4 were obtained. Drugs such as alemtuzumab and marimastat were negatively related to expression of the DEGs and might be useful drugs for RA treatment. In addition, most DEGs were involved in innate immune response (e.g., TYROBP, CCL5, CXCL10, FCGR1A, and FCGR3B) and phagosome pathway (e.g., CTSS). We suggested that miR-101 that regulated DUSP1, IRF1 TF that regulated CXCR4, as well as DEGs as TYROBP and CTSS might contribute to the RA pathogenesis. In addition, anti-inflammatory agent alemtuzumab and matrix metalloproteinase inhibitor marimastat might be useful drugs for RA treatment through functioning on their target genes.
30411174 Should a patient with rheumatoid arthritis be a kidney donor? 2019 Jan We cared for a woman with sero-positive rheumatoid arthritis (RA), in clinical remission on oral methotrexate (MTX) and hydroxychloroquine, who wished to donate a kidney to a brother with end-stage renal disease (ESRD). We could find scant literature about this unusual clinical circumstance, and therefore review pertinent aspects of renal disease in RA, perioperative medical management, maintenance of disease remission, outcomes for RA patients who have donated kidneys, and relevant ethical issues. Renal complications in RA are not uncommon, with as many as 50% of patients at risk of reduced eGFR. This reflects anti-rheumatic and analgetic medication use (non-steroidal anti-inflammatory drugs, acetaminophen, DMARDs [cyclosporine and, historically, D-penicillamine and gold compounds], and others), glomerulitis, interstitial nephritis, complicating Sjogren's syndrome, vasculitis, or amyloidosis, and/or emergence of an "overlap" syndrome or other rheumatic disorder. The literature suggests that MTX need not be interrupted for surgery. The risk of perioperative infection to our patient would be low and remission should be sustained. We are aware of one study of six patients with RA who donated kidneys; they experienced no complications, ESRD, or deaths after a median follow-up of 8.2 years. Our ethical responsibilities are to balance patient autonomy of decision-making while assuring clinical beneficence and minimizing potential maleficence. Our perspective was that it would not be unreasonable to support this patient donating a kidney if, when fully informed, that remained her wish.
31544586 Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis. 2020 Mar Objectives: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid arthritis (RA) pathogenesis. We investigated PAD activation by serum (PAD(Act)) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.Method: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PAD(Act) were evaluated by Mann-Whitney U and chi-squared tests. Changes in PAD(Act) levels were compared using the Wilcoxon signed-rank test.Results: PAD(Act) positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PAD(Act)-positive were younger than PAD(Act)-negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PAD(Act) levels were higher in patients than in controls (8768 [7491, 11 393] vs 7046 [6347, 7906], p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.Conclusion: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA.
30909750 MALAT1-Driven Inhibition of Wnt Signal Impedes Proliferation and Inflammation in Fibroblas 2019 Aug Fibroblast-like synoviocytes (FLSs) participate in the pathogenesis of rheumatoid arthritis (RA). Emerging evidence has highlighted the role of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and its potential involvement in RA. In this study, we test the hypothesis that the MALAT1 might inhibit proliferation and inflammatory response of FLSs in RA. The expression of MALAT1 was examined in synovial tissues from patients with RA. The effect of MALAT1 on cultured FLSs was analyzed by introducing overexpressed MALAT1 or short hairpin RNA (shRNA) against MALAT1. To validate whether methylation of CTNNB1 promoter was affected by MALAT1 alternation, we assessed the recruitment of DNA methyltransferases to CTNNB1 promoter. In cultured FLSs with shRNA-mediated CTNNB1 knockdown or activated Wnt signaling, we found the interaction between CTNNB1 and Wnt signaling. MALAT1 expression was reduced in synovial tissues of RA. MALAT1 could bind to CTNNB1 promoter region and recruit methyltransferase to promote CTNNB1 promoter methylation, thereby inhibiting CTNNB1. Notably, MALAT1 could suppress the transcription and expression of CTNNB1, thereby modulating the Wnt signaling pathway. Silenced MALAT1 stimulated the nucleation of β-catenin and the secretion of inflammatory cytokines including interleukin-6, interleukin-10, and tumor necrosis factor-α. Additionally, shRNA-mediated MALAT1 silencing elevated proliferation and suppressed apoptosis of FLSs accompanied. These findings provide evidence for the inhibitory effect of MALAT1 on proliferation and inflammation of FLSs by promoting CTNNB1 promoter methylation and inhibiting the Wnt signaling pathway. Therefore, this study provides a candidate therapeutic target for RA.
31858209 A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation 2020 Mar Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = - 0.4, p = 0.009) and between vWF:Ag and TH2 (R = - 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2(baseline) = 26.9 s vs. TH2(4weeks) = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH2(8weeks) = 40.5, p = 0.026; TH2(12weeks) = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AH(baseline) = 1599 Perfusion Units [PU] vs. AH(8weeks) = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.
30847560 Association between disease activity measured by RAPID3 and health-related quality of life 2019 May Routine assessment of patient index data 3 (RAPID3) is a simple, valid and reliable tool designed to measure disease activity in patients with rheumatoid arthritis (RA). RA causes significant disability and diminishes health-related quality of life (HR-QoL). The aim of this study was to investigate how RAPID3 is related to HR-QoL in patients with RA. In this cross-sectional study performed at the tertiary outpatient clinic 68 consecutive patients (58 females, and 10 males) with established RA were enrolled. RAPID3 and EuroQoL-5D-3L (EQ-5D-3L) were used to measure disease activity and quality of life, respectively. Alongside, demographic and clinical data were obtained, as well as HAQ-DI as a measure of physical function, and Steinbrocker's score for radiographic damage. To test the relationships among RAPID3 and study variables we used the Pearson product-moment correlation coefficient, with the significance was set at P < 0.05. Linear and forward stepwise regression was used to show how variables of interest contributed to RAPID3. The mean value of RAPID3 (standard deviation, SD) was 14.12 (± 5.21), while the median (IQR) value of EQ-5D-3L was 0.51 (0.62-0.23). There was a high significant correlation (r = - 0.73) between RAPID3 scores and EQ-5D-3L. Among the other variables of interest, the strongest correlation was found between RAPID3 and intensity of pain (r = 0.88), while the EQ-5D-3L and pain were moderately correlated (r = - 0.68). In evaluating the influence of variables of interest on RAPID3, a forward stepwise regression model was constructed to evaluate whether VAS pain, EQ-5D-3L and EQ-VAS predicted RAPID3. The given variables significantly explained approximately 81% of the variation in RAPID3. Based on the results of this study RAPID3, a simple and practical tool to assess disease activity, reflects well HR-QoL in patients with established RA.
30072114 Searching for a prodrome for rheumatoid arthritis in the primary care record: A case-contr 2019 Apr BACKGROUND: Rheumatoid arthritis (RA) has articular and non-articular manifestations. Early, intensive treatment has substantial benefit for both. This requires patients be identified as soon as symptoms develop. OBJECTIVES: To determine whether selected signs and symptoms can be identified in the primary care records of patients prior to a formal diagnosis of RA being made and, if so, how early they can be identified. METHODS: A case-control study was constructed within the UK Clinical Practice Research Datalink (CPRD). 3577 individuals with 'definite' RA, were matched to 14,287 individuals without inflammatory arthritis. An index date was established (i.e., date general practitioner (GP) first appeared to suspect RA). Rates of consultation and consultations for suspected early RA symptoms were compared in cases and controls in the two years prior to the index date using conditional logistic regression, adjusted for number of consultations. RESULTS: The mean (standard deviation) age of participants was 58.8 (14.5) years and 66.8% were female. Rates of any consultation were significantly higher in RA cases than in controls for at least two years prior to the index date. Cases were more likely to have a pre-diagnosis coded consultation for joint, and particularly hand symptoms (aOR 11.44 (9.60, 13.63)), morning stiffness (8.10 (3.54, 18.5)), carpal tunnel syndrome (4.57 (3.54, 5.88)) and other non-articular features. CONCLUSIONS: In patients who develop RA, GP consultation rates are higher for at least two years prior to the first recorded suspicion of RA. This study highlights symptoms that should raise a GP's index of suspicion for RA.
30246572 The time-sequential changes of risk factors for adult T-cell leukemia development in human 2019 Sep Objective: This study aimed to investigate the time-sequential changes of risk factors for adult T-cell leukemia (ATL) development in human T-cell leukemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Methods: HTLV-1 infection was screened using particle agglutination assay and confirmed via western blotting in 365 RA patients. Twenty-three HTLV-1-positive RA patients were included in the study cohort. Blood samples were obtained from these patients at each observation time point. The values of HTLV-1 proviral load (PVL) and serum soluble IL-2 receptor (sIL2-R), which are risk factors for ATL development, were measured using real-time PCR and enzyme immunoassay, respectively. Results: The study cohort comprised 79 person-years. The median HTLV-1 PVL and sIL2-R values of the HTLV-1-positive RA patients were 0.44 copies per 100 white blood cells (WBCs) and 406 U/mL, respectively. Three HTLV-1-positive RA patients showed a high PVL value. No remarkable changes were observed in the PVL and sIL2-R values during the observation period. However, one elderly HTLV-1-positive RA patient who had a high PVL value developed ATL during treatment with methotrexate and infliximab. Conclusion: A thorough clinical assessment of the risk factors for ATL development may be necessary in daily clinical practice for RA patients in HTLV-1-endemic areas in Japan.
30836801 Radiographic and clinical outcomes following etanercept monotherapy in Japanese methotrexa 2020 Mar Objectives: Compare outcomes with methotrexate (MTX) or etanercept (ETN) monotherapy in Japanese patients with active rheumatoid arthritis (RA) who were MTX-naïve or with intolerance or inadequate response to prior MTX (MTX-IR).Methods: Post hoc analysis of a phase 3 study comparing MTX, ETN 10 mg twice weekly, and ETN 25 mg twice weekly in Japanese patients with RA. Disease activity was evaluated using American College of Rheumatology (ACR) scores and 28-joint Disease Activity Score (DAS28), radiographic progression evaluated using van der Heijde's modified Total Sharp Score (mTSS), and functional status evaluated using Health Assessment Questionnaire Disability Index (HAQ-DI).Results: Among MTX-naïve and MTX-IR patients, greater proportions of those randomized to either ETN group achieved ACR20, ACR50, ACR70, DAS28 ≤3.2 or <2.6, clinically relevant inhibition of mTSS changes, and reductions in HAQ-DI compared with MTX at the majority of time points. There were very few clinically meaningful differences between ETN groups for any of the variables evaluated.Conclusion: ETN monotherapy was more effective than MTX in both MTX-naïve and MTX-IR patients, with very few clinically meaningful differences between ETN 10 mg and ETN 25 mg when given twice weekly. The relative benefits of ETN were greater in MTX-naïve patients than MTX-IR patients.ClinicalTrials.gov identifierNCT00445770.
30845171 Gene expression profiling meta-analysis reveals novel gene signatures and pathways shared 2019 Tuberculosis (TB) is among the leading causes of death by infectious diseases. An epidemiological association between Mycobacterium tuberculosis infection and autoimmune diseases like rheumatoid arthritis (RA) has been reported but it remains unclear if there is a causal relationship, and if so, which molecular pathways and regulatory mechanisms contribute to it. Here we used a computational biology approach by global gene expression meta-analysis to identify candidate genes and pathways that may link TB and RA. Data were collected from public expression databases such as NCBI GEO. Studies were selected that analyzed mRNA-expression in whole blood or blood cell populations in human case control studies at comparable conditions. Six TB and RA datasets (41 active TB patients, 33 RA patients, and 67 healthy controls) were included in the downstream analysis. This approach allowed the identification of deregulated genes that had not been identified in the single analysis of TB or RA patients and that were co-regulated in TB and RA patients compared to healthy subjects. The genes encoding TLR5, TNFSF10/TRAIL, PPP1R16B/TIMAP, SIAH1, PIK3IP1, and IL17RA were among the genes that were most significantly deregulated in TB and RA. Pathway enrichment analysis revealed 'T cell receptor signaling pathway', 'Toll-like receptor signaling pathway,' and 'virus defense related pathways' among the pathways most strongly associated with both diseases. The identification of a common gene signature and pathways substantiates the observation of an epidemiological association of TB and RA and provides clues on the mechanistic basis of this association. Newly identified genes may be a basis for future functional and epidemiological studies.
31462627 Platelet/Lymphocyte, Lymphocyte/Monocyte, and Neutrophil/Lymphocyte Ratios as Biomarkers i 2019 Aug 29 BACKGROUND The objective of this study was to assess the diagnostic value of platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and neutrophil/lymphocyte ratio (NLR) as biomarkers in patients with rheumatoid arthritis (RA) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). MATERIAL AND METHODS Demographic and laboratory data were acquired for 198 RA and 103 RA-ILD patients and 290 healthy controls. The subjects were categorized into female and male groups and further subcategorized based on age into <60 years and ≥60 years subgroups. One-way analysis of variance (ANOVA), receiver operating characteristics (ROC), Pearson analysis, multiple linear regression analysis, and logistic regression analysis were performed to analyze the association of PLR, NLR, and LMR with RA and RA-ILD. RESULTS Mean PLR and NLR were lowest in the control group, followed by the RA and RA-ILD groups (p<0.05). Mean LMR was lowest in the RA-ILD group, followed by the RA and control groups (p<0.05). The area under the ROC (AUROC) values of the PLR to distinguish between RA and controls, RA-ILD and controls, and RA-ILD and RA were 0.676, 0.776, and 0.650, respectively (p<0.001). Multiple linear regression analysis suggested a significantly positive association between the level of PLR and the level of DAS28 (p<0.001). The odds ratio of PLR was 1.101 for RA (p=0.023) and 1.217 for RA-ILD (p<0.001) when compared to the controls. CONCLUSIONS PLR may be applied as a new biomarker for predicting and diagnosing RA and RA-ILD and for distinguishing RA-ILD patients from RA patients and healthy subjects.
30935255 Patients opinion and adherence to antimalarials in lupus erythematosus and rheumatoid arth 2020 May Objective: To obtain the opinion of patients with rheumatoid arthritis or lupus erythematosus about the use of antimalarials through questionnaires and to evaluate their adherence to medication.Methods: A cross-sectional study of patients treated with antimalarial medication for a period equal to or longer than 1 year attended between November 2012 and October 2014. A structured questionnaire with 12 questions was filled out.Results: Among 300 patients examined, 92% (275) used medication regularly. Hydroxychloroquine was used by 55% (166) of patients, chloroquine by 25% (75), and 20% (59) reported using both medications at different moments. Most of the patients (221 or 74%) were using medication seven days a week and had taken it for a period longer than 5 years; 61% (182) considered the treatment good and said, 21% (63) said, 'It is good, but I'm afraid of taking it'. Most of the patients (70% or 211) did not report any adverse symptoms. Their main claim was related to blurred vision, which was solved by a refraction examination.Conclusions: Fear has been a factor that makes adherence to treatment difficult. Making patients aware of the importance of the treatment is strongly relevant because antimalarials are well tolerated.
28919284 MMP-8 and TIMP-1 are associated to periodontal inflammation in patients with rheumatoid ar 2019 Jun BACKGROUND: Aim of this cross-sectional study was the investigation of associations between different rheumatoid arthritis (RA)-related blood parameters and periodontal condition as well as selected periodontal pathogenic bacteria in RA patients under methotrexate (MTX) immunosuppression. METHODS: Periodontal probing depth (PPD), bleeding on probing (BOP) and clinical attachment loss (CAL) were assessed. Periodontal condition was classified into: no/mild and moderate or severe periodontitis (P). Prevalence of selected periodontal pathogenic bacteria and concentration of matrix metalloproteinase 8 (MMP-8) was assessed from the gingival crevicular fluid (GCF) using PCR and ELISA, respectively. Blood samples were analyzed for the concentration of selected rheumatoid parameters. STATISTICAL ANALYSIS: t-test, Mann-Whitney-U-Test, exact Fisher tests or chi square test (p < 0.05). RESULTS: Fifty-six patients (mean age 55.07 years, 34 P, 22 no P) were included. While prevalence of periodontal pathogenic bacteria was higher in P patients, no substantial association of bacteria with blood parameters was found. In periodontal diseased participants, MMP-8 concentration in GCF (6.22 ± 7.01 vs. 15.99 ± 13.49; p < 0.01) and blood (2.60 ± 3.57 vs. 5.52 ± 5.92; p < 0.01) was increased, while no correlation between GCF and blood was found (Spearman's rho: 0.175; p = 0.23). Furthermore, higher blood concentrations of MMP-8 and tissue inhibitor of MMP (TIMP-1) were detected in patients with increased periodontal inflammation (BOP positive, p < 0.01). CONCLUSION: Periodontal inflammation appears associated to MMP-8 and TIMP-1 in blood. Thereby, clinical interaction between periodontal conditions, periodontal pathogenic bacteria and RA-related cytokines remain unclear.