Browse

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

ID PMID Title PublicationDate abstract
27720921 Hesperidin derivative-11 inhibits fibroblast-like synoviocytes proliferation by activating 2017 Jan 5 Hesperidin (HDN), a flavanone glycoside derived from the citrus cultivation, has a multitude of pharmacological properties, which include antioxidant, anti-inflammatory, hypolipidaemic and anti-carcinogenic actions, but the underlying mechanisms by which treatment of HDN attenuates Rheumatoid Arthritis (RA) remain elusive. Here we engaged to determine whether Hesperidin derivative-11(HDND-11), a HDN derivative with enhanced water-solubility and bioavailability, is effective on treating arthritis in rats. In this study, results of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetra-zolium bromide (MTT) assay and Flow cytometry indicated that administration of HDND-11 inhibited proliferation of fibroblast-like synoviocytes (FLS). Results of Western blot, Real-time quantitative PCR (RT-qPCR) analysis and Immunofluorescence staining demonstrated that HDND-11 was able to up-regulate the expression of Secreted frizzled-related proteins 2 (SFRP2) and diminish DNA methyltransferase 1(DNMT1) expression. We also identified that the effect of DNMT1 inhibition was completely similar to the effects of HDND-11 on SFRP2 gene expression. Furthermore, our results indicated that treatment with HDND-11 could suppress activation of Wnt pathway. Taken together, we found that the HDND-11diminished inhibitory effect of DNMT1 on SFRP2, thereby down-regulated β-catenin expression and inhibited the activation of Wnt signaling pathways to inhibit FLS growth.
28535544 Portuguese Recommendations for the use of biological therapies in patients with rheumatoid 2017 Jun 1 OBJECTIVE: To update the recommendations for the treatment of Rheumatoid Arthritis (RA) with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 10 recommendations were discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. RESULTS: These recommendations cover general aspects as shared decision, prospective registry in Reuma.pt, assessment of activity and RA impact and treatment objective. Consensus was also achieved regarding specific aspects as initiation of biologic therapy, assessment of response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with biological therapies in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.
28783699 Help not wanted in the joint. 2017 Mar 3 A newly discovered T cell subset that helps B cells is expanded in joints of rheumatoid arthritis patients.
28915723 Correction: Increased autophagy in fibroblast-like synoviocytes leads to immune enhancemen 2017 Aug 22 [This corrects the article DOI: 10.18632/oncotarget.14331.].
28781502 Pharmaceutical Approval Update. 2017 Aug Naldemedine (Symproic) for opioid-induced constipation; deutetrabenazine (Austedo) for chorea associated with Huntington's disease; and infliximab-abda (Renflexis), a Remicade biosimilar, for the treatment of Crohn's disease, rheumatoid arthritis, and other diseases.
29183769 TPL2 kinase action and control of inflammation. 2018 Mar Tumor progression locus 2 (TPL2, also known as COT or MAP3K8) is a mitogen-activated protein kinase kinase (MAP3K) activated downstream of TNFαR, IL1R, TLR, CD40, IL17R, and some GPCRs. TPL2 regulates the MEK1/2 and ERK1/2 pathways to regulate a cascade of inflammatory responses. In parallel to this, TPL2 also activates p38α and p38δ to drive the production of various inflammatory mediators in neutrophils. We discuss the implications of this finding in the context of various inflammatory diseases.
28815115 Discovering adverse drug events combining spontaneous reports with electronic medical reco 2017 The use of multiple data sources has been preferred in the surveillance of adverse drug events due to shortcomings of using only a single source. In this study, we proposed a framework where the ADEs associated with interested drugs are systematically discovered from the FDA's Adverse Event Reporting System (AERS), and then validated through mining unstructured clinical notes from Electronic Medical Records (EMRs). This framework has two features. First, a higher priority was given to clinical practice during signal detection and validation. Second, the normalization by NLP facilitated the interoperation between AERS-DM and the EMR. To demonstrate this methodology, we investigated potential ADEs associated with drugs (class level) for rheumatoid arthritis (RA) patients. The results demonstrated the feasibility and sufficient accuracy of the framework. The framework can serve as the interface between the informatics domain and the medical domain to facilitate ADE discovery.
28741433 Immune System Involvement in Specific Pain Conditions. 2017 Jan Chronic pain is a significant problem worldwide and is the most common disability in the United States. It is well known that the immune system plays a critical role in the development and maintenance of many chronic pain conditions. The involvement of the immune system can be through the release of autoantibodies, in the case of rheumatoid arthritis, or via cytokines, chemokines, and other inflammatory mediators (i.e. substance P, histamine, bradykinin, tumor necrosis factor, interleukins, and prostaglandins). Immune cells, such as T cells, B cells and their antibodies, and microglia are clearly key players in immune-related pain. The purpose of this review is to briefly discuss the immune system involvement in pain and to outline how it relates to rheumatoid arthritis, osteoarthritis, fibromyalgia, complex regional pain syndrome, multiple sclerosis, and diabetic neuropathy. The immune system plays a major role in many debilitating chronic pain conditions and we believe that animal models of disease and their treatments should be more directly focused on these interactions.
28280915 [Orthoses and assistive devices in rheumatology : Prevention of disability, support of res 2017 Apr Due to the frequent presence of comorbidities in patients suffering from rheumatism with increased perioperative risk factors, conservative treatment is often needed. Besides pharmacological treatment, physiotherapy and occupational therapy, a variety of orthoses are available depending on the individual indications. They can be used to stabilize or support joints, limit the range of motion, prevent unphysiological movements or provide relief for affected limbs. In order to choose the right kind of orthosis, the physician should know the underlying cause of disease. Furthermore, for patients with rheumatism many devices are available for daily living that use ergonomic handles or improved leverage effects to compensate for the often severe limitations and to improve the quality of life.
28861004 The Temporal Relationship between Arterial Stiffening and Blood Pressure Is Modified by Me 2017 Background: The temporal relationship between arterial stiffness and blood pressure (BP) may vary depending on age and other clinical and demographic factors. Since both BP and arterial stiffness are also affected by inflammatory processes, we examined the temporal arterial stiffness-BP relationship in patients with rheumatoid arthritis (RA) treated with either methotrexate (MTX), an anti-rheumatic agent shown to reduce cardiovascular risk in meta-analyses, or other disease-modifying anti-rheumatic drugs (DMARDs). Methods: Measurements of clinic and 24-h peripheral and central systolic and diastolic BP (SBP and DBP), and pulse wave velocity (PWV) were assessed in RA patients on stable treatment with either MTX ± other DMARDs (MTX group, n = 41, age 61 ± 14 years, 73% females) or other DMARDs (non-MTX group, n = 18, age 65 ± 13 years, 89% females). Measurements were performed at baseline and after 8 months. The temporal relationships were examined using cross-lagged path analysis with models that included age, sex, body mass index, prednisolone, and folic acid use and 28-joint disease activity score. Results: There were significant differences in the temporal arterial stiffness-BP relationships between those in the MTX and DMARD groups. A higher PWV at baseline caused a significant increase in 6 out of 8 different measures of SBP at 8 months amongst those treated with DMARDs (standardized β, range = 0.54-0.66, p < 0.003 for each) and 3 out of 8 different measures of DBP (standardized β, range = 0.52-0.61, p < 0.003 for each) but was not associated with either SBP or DBP at 8 months amongst those treated with MTX. The difference in the effect of baseline PWV on 8-month BP between the 2 groups was also significant (p < 0.003) for 4 measures including clinic peripheral SBP (β = 7.0, 95% CI = 2.8-11.1 mmHg per 1 m/s higher baseline PWV; p < 0.001). Conclusions: Higher arterial stiffness preceded increases in BP in subjects with RA treated with DMARDs, but these effects did not occur amongst those treated with MTX. The different effects were seen mostly in measures of SBP but were also present in some measures of DBP. Our findings suggest MTX may confer a protective effect against stiffness mediated increases in BP in patients with RA.
28878153 High-Throughput Study of the Effects of Celastrol on Activated Fibroblast-Like Synoviocyte 2017 Sep 6 Celastrol, a natural triterpene, exhibits potential anti-inflammatory activity in a variety of inflammatory diseases. The present study aimed to investigate its biological effect on activated fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). The primary FLSs of the synovial tissues were obtained from synovial biopsies of patients with RA. The normal human FLS line (HFLS) was used as a control. After the RA-FLSs and HFLSs were treated with or without celastrol, various approaches, including the WST-1 assay, transwell assay, real-time PCR and ELISA analysis, were performed to estimate proliferation, invasion and expression of pro-inflammatory cytokines of the RA-FLSs. Microarray analysis was performed to screen for differentially expressed genes in RA-FLSs before and after celastrol treatment. The results showed that treatment of celastrol attenuated both the proliferation and invasion of the RA-FLSs. The expression of several chemokine genes, including CCL2 , CXCL10 , CXCL12 , CCR2 and CXCR4 , was significantly changed after celastrol treatment. The genes involved in the NF-κB signaling pathway appeared to be regulated by celastrol.
29119006 Cost-utility of COBRA-light versus COBRA therapy in patients with early rheumatoid arthrit 2017 OBJECTIVE: To evaluate if COmbinatie therapie Bij Reumatoïde Artritis (COBRA)-light therapy is cost-effective in treating patients with early rheumatoid arthritis (RA) compared with COBRA therapy. METHODS: This economic evaluation was performed next to the open-label, randomised non-inferiority COBRA-light trial in 164 patients with early RA. Non-responders to COBRA or COBRA-light received etanercept (50 mg/week) for 3-6 months. The societal perspective analysis took medical direct, non-medical direct and indirect costs into account. Costs were measured with patient cost diaries for the follow-up period of 52 weeks. Bootstrapping techniques estimated uncertainty around the cost-effectiveness ratios, presented in cost-effectiveness planes. RESULTS: 164 patients were randomised to either COBRA or COBRA-light strategy. At week 52, COBRA-light proved to be non-inferior to COBRA therapy on all clinical outcome measures. The results of the base-case cost-utility analysis (intention-to-treat analyses) revealed that COBRA-light strategy is more expensive (k€9.3 (SD 0.9) compared with COBRA (k€7.2 (SD 0.8)), but the difference in costs were not significant (k€2.0; 95% CI -0.3 to 4.4). Also, both strategies produced similar quality-adjusted life-years (QALYs). The sensitivity analyses showed robustness of these results. In a per-protocol sensitivity analysis, in which costs of etanercept were assumed to be provided as prescribed according to protocol, both arms had much higher costs: COBRA-light: k€11.5 (8.3) compared with k€8.5 (6.8) for COBRA, and the difference in costs was significant (k€2.9; 0.6 to 5.3). CONCLUSIONS: In the base-case cost-utility analysis, the two strategies produced similar QALYs for similar costs. But it is anticipated that if protocol had been followed correctly, the COBRA-light strategy would have been more costly due to additional etanercept costs, for a limited health gain. Given the limited added benefit and high costs of starting etanercept in the presence of low disease activity in our trial, such a strategy needs better justification than is available now. TRIAL REGISTRATION NUMBER: 55552928, Results.
28790485 Bone Wasn't Built in a Day: Destruction and Formation of Bone in the Rheumatic Diseases. 2017 The hallmark of rheumatoid arthritis is synovitis, or inflammation of synovial tissues lining joints. Synovitis in rheumatoid arthritis promotes destruction of articular bone by inducing the differentiation and function of osteoclasts, leading to significant patient morbidity. The cell types and pathways mediating articular bone destruction have now been elucidated and the critical role of receptor activator of nuclear factor-kappa B ligand has been recognized, leading to the identification of new targets for the protection of articular bone. Synovitis not only promotes bone destruction, but also inhibits the ability of bone-forming osteoblasts to repair bone. In stark contrast, inflammation in spondyloarthritis, including ankylosing spondylitis, promotes bone formation at periosteal sites, resulting in pain and decreased motion of the spine and joints. Local anatomic factors contribute to these distinct outcomes for bone and anabolic pathways regulating bone formation are now being investigated to identify novel targets for prevention of abnormal bone formation.
28099214 Rheumatoid Arthritis: Selecting Monotherapy Versus Combination Therapy. 2017 Jan 18 The overall goal of therapy for patients with rheumatoid arthritis (RA) is to achieve low disease activity or remission and to prevent or control joint damage, prevent loss of function, and decrease pain. However, many patients with RA do not have the disease adequately controlled, and only a minority attain consistent remission. To successfully treat to target, rheumatologists need practical guidance to select monotherapy and combination therapy regimens based on available data. Differences in study design, dosing regimens, and data from defined and specific patient populations pose challenges to clinicians who treat patients with diverse characteristics and needs. Because clinical trial results are not always translated into real-life clinical practice, this article synthesizes evidence from all sources, including meta-analyses of clinical trial data, data from patient registries in RA, and results of pragmatic trial designs. Practical guidance with these strategies is demonstrated using application in patient case scenarios, which will enable rheumatology health care professionals to more easily compare the effectiveness and safety of RA treatment strategies as experienced in real-life practice settings. Combination therapy is important for most patients with RA; however, there remain no clear guidelines for selecting the most appropriate combination strategy.
28410817 Medication adherence and persistence over time with self-administered TNF-alpha inhibitors 2017 Oct OBJECTIVE: Self-injectable TNF inhibitors are increasingly used early in the chronic treatment of moderate to severe rheumatologic conditions. We estimated medication adherence/persistence over time following initiation in young adult and older adult patients with rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis. METHODS: We conducted a retrospective cohort study of patients aged 18+ years newly initiating etanercept, adalimumab, certolizumab pegol, or golimumab using the Truven Health MarketScan Database between 2009 and 2013. Pharmacy dispensing data were used to calculate 12-month medication possession ratios (MPR) and determine adherence (MPR ≥ 0.80) for up to 3 years after starting therapy. Persistence over each 12-month interval was defined as not having a ≥92-day treatment gap. Multivariable generalized estimating equation models were used to calculate odds ratios (OR) and robust 95% confidence intervals (CI) for associations between patient characteristics and repeated adherence/persistence measures over time. RESULTS: Among 53,477 new users, 14% were young adults (18-34 years), 49% middle-aged (35-54 years), and 37% older adults (55+ years). Overall, 37% of patients were adherent and 83% were persistent in the first year of therapy. The lowest adherence (17%) and persistence (70%) were observed among young adult patients by Year +3. Compared to older adults, middle-aged (OR = 0.73, 95% CI: 0.71-0.76) and young adults (OR = 0.50, 95% CI: 0.47-0.53) were less likely to be adherent. Higher Charlson comorbidity scores, hospitalizations, and emergency department visits were associated with non-adherence/non-persistence. CONCLUSIONS: We observed low adherence to self-administered TNF inhibitors but most patients remained persistent over time. Further efforts to improve adherence in young adults and patients with greater comorbidity are needed.
29209330 The Enigma of Heat Shock Proteins in Immune Tolerance. 2017 The fundamental problem of autoimmune diseases is the failure of the immune system to downregulate its own potentially dangerous cells, which leads to destruction of tissue expressing the relevant autoantigens. Current immunosuppressive therapies offer relief but fail to restore the basic condition of self-tolerance. They do not induce long-term physiological regulation resulting in medication-free disease remissions. Heat shock proteins (HSPs) have shown to possess the capacity of inducing lasting protective immune responses in models of experimental autoimmune diseases. Especially mycobacterial HSP60 and HSP70 were shown to induce disease inhibitory IL-10-producing regulatory T cells in many different models. This in itself may seem enigmatic, since based on earlier studies, HSPs were also coined sometimes as pro-inflammatory damage-associated molecular patterns. First clinical trials with HSPs in rheumatoid arthritis and type I diabetes have also indicated their potential to restore tolerance in autoimmune diseases. Data obtained from the models have suggested three aspects of HSP as being critical for this tolerance promoting potential: 1. evolutionary conservation, 2. most frequent cytosolic/nuclear MHC class II natural ligand source, and 3. upregulation under (inflammatory) stress. The combination of these three aspects, which are each relatively unique for HSP, may provide an explanation for the enigmatic immune tolerance promoting potential of HSP.
29190882 Functional polymorphisms in pre-miR146a and pre-miR499 are associated with systemic lupus 2017 Nov 3 Recently, different microRNA (miRNA) gene polymorphisms have been evaluated in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves' disease (GD). In the present study, we examined three single-nucleotide polymorphisms (SNPs) located in the pre-miR-146a (rs2910164G/C), pre-miR-196a-2 (rs11614913C/T), and pre-miR-499 (rs3746444A/G) genes. Our study population included 900 Mexican patients with RA, SLE, or GD, as well as 486 healthy control individuals with no family history of inflammatory or autoimmune diseases. Genotyping was performed using TaqMan probes and a 5' exonuclease assay. None of the investigated SNPs were associated with RA or GD susceptibility under any genetic model (co-dominant, recessive, or dominant). Genotype and allele frequencies of the miR-196a-2 rs11614913C/T polymorphism were similar between SLE cases and controls. In contrast, the miR-146a rs2910164G/C and miR-499 rs3746444A/G polymorphisms were associated with SLE susceptibility. These SNPs were not associated with lupus nephritis (LN). Our results suggest that polymorphisms in miR-146a, miR-196a-2, and miR-499 are not associated with RA or GD susceptibility. This is the first report documenting that the miR-146a rs2910164G/C and miR-499 rs3746444 polymorphisms are associated with SLE susceptibility but not with LN.
29277578 Perceptions of patients with rheumatic diseases treated with subcutaneous biologicals on t 2019 Nov OBJECTIVE: To investigate, in Spanish patients with rheumatic diseases treated with subcutaneous biological drugs, their sources of information, which sources they consider most relevant, and their satisfaction with the information received in the hospital. METHODS: Rheumatologists from 50 hospitals handed out an anonymous survey to 20 consecutive patients with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis treated with subcutaneous biologicals. The survey was developed ad hoc by 4 rheumatologists and 3 patients, and included questions with closed-ended responses on sources of information and satisfaction. RESULTS: The survey was handed-out to 1,000 patients, 592 of whom completed it (response rate: 59.2%). The rheumatologist was mentioned as the most important source of information (75%), followed by the primary care physician, nurses, and electronic resources; 45.2% received oral and written information about the biological, 46.1% oral only, and 6.0% written only; 8.7% stated that they had not been taught to inject the biological. The percentage of patients satisfied with the information received was high (87.2%), although the satisfaction was lower in relation to safety. If the information came from the rheumatologist, the satisfaction was higher (89.6%) than when coming from other sources (59.6%; P<.001). Satisfaction was also higher if the information was provided orally and written (92.8%) than if provided only orally (86.1%; P=.013); 45.2% reported having sought information from sources outside the hospital. CONCLUSIONS: The rheumatologist is key in transmitting satisfactory information on biological treatment to patients. He or she must also act as a guide, since a high percentage of patients seeks information in other different sources.
29629295 In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera 2018 Mar BACKGROUND: The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. METHODS: Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. RESULTS: The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. CONCLUSION: Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.
28223263 Apps for People With Rheumatoid Arthritis to Monitor Their Disease Activity: A Review of A 2017 Feb 21 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis requiring long-term treatment with regular monitoring by a rheumatologist to achieve good health outcomes. Since people with RA may wish to monitor their own disease activity with a smartphone app, it is important to understand the functions and quality of apps for this purpose. OBJECTIVE: The aim of our study was to assess the features and quality of apps to assist people to monitor their RA disease activity by (1) summarizing the available apps, particularly the instruments used for measurement of RA disease activity; (2) comparing the app features with American College of Rheumatology and European League against Rheumatism (ACR and EULAR) guidelines for monitoring of RA disease activity; and (3) rating app quality with the Mobile App Rating Scale (MARS). METHODS: Systematic searches of the New Zealand iTunes and Google Play app stores were used to identify all apps for monitoring of RA disease activity that could be used by people with RA. The apps were described by both key metadata and app functionality. App adherence with recommendations for monitoring of RA disease activity in clinical practice was evaluated by identifying whether apps included calculation of a validated composite disease activity measure and recorded results for future retrieval. App quality was assessed by 2 independent reviewers using the MARS. RESULTS: The search identified 721 apps in the Google Play store and 216 in the iTunes store, of which 19 unique apps met criteria for inclusion (8 from both app stores, 8 iTunes, and 3 Google Play). In total, 14 apps included at least one validated instrument measuring RA disease activity; 7 of 11 apps that allowed users to enter a joint count used the standard 28 swollen and tender joint count; 8 apps included at least one ACR and EULAR-recommended RA composite disease activity (CDA) measure; and 10 apps included data storage and retrieval. Only 1 app, Arthritis Power, included both an RA CDA measure and tracked data, but this app did not include the standard 28 tender and swollen joint count. The median overall MARS score for apps was 3.41/5. Of the 6 apps that scored ≥4/5 on the overall MARS rating, only 1 included a CDA score endorsed by ACR and EULAR; however, this app did not have a data tracking function. CONCLUSIONS: This review found a lack of high-quality apps for longitudinal assessment of RA disease activity. Current apps fall into two categories: simple calculators primarily for rheumatologists and data tracking tools for people with RA. The latter do not uniformly collect data using validated instruments or composite disease activity measures. There is a need for appropriate, high-quality apps for use by rheumatologists and patients together in co-management of RA.