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

ID PMID Title PublicationDate abstract
27293066 Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis 2016 Sep This review highlights the story of how methotrexate (MTX), a drug discovered for the treatment of childhood leukemia, became the mainstay of treatment and the standard-of-care for rheumatoid arthritis (RA) and was also found useful for several additional related rheumatological diseases. As against several synthetic disease-modifying antirheumatic drugs (csDMARDs) for treating RA that were discovered serendipitously, the use of low-dose MTX (LD-MTX) was based on sound reasoning and astute observations made in the 1940s and 1950s. The difference between high-dose MTX (HD-MTX) used in the treatment of childhood leukaemia and other malignancies as against LD-MTX used in rheumatology is emphasized.
27964796 Vasculitis and inflammatory arthritis. 2016 Oct Vasculitis has been described in most types of inflammatory arthritis. The best described and most widely recognised form is rheumatoid vasculitis. The incidence of systemic rheumatoid vasculitis has declined significantly following the general early use of methotrexate in the 1990s, and it is now a rare form of vasculitis. Treatment of rheumatoid vasculitis is conventionally with glucocorticoids and cyclophosphamide, but there is an increasing role for rituximab similar to that in other types of vasculitis. Despite these developments the mortality of rheumatoid vasculitis remains high. Vasculitis in other types of inflammatory arthritis is less well described and the treatment remains empirical.
27169879 Macrophage migration inhibitory factor: a potential therapeutic target for rheumatoid arth 2016 Jul Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients.
27812955 Differential Effects of Inflammation on Bone and Response to Biologics in Rheumatoid Arthr 2016 Dec PURPOSE OF REVIEW: We review the pathways, cytokines, and concepts important to the pathogenesis of bone resorption and formation in rheumatoid arthritis (RA) and spondyloarthritis (SpA). RECENT FINDINGS: Research in bone biology has shed light on the pathogenesis of the joint destruction that occurs in RA and in peripheral SpA. However, understanding the mechanisms behind the bone formation seen in peripheral and axial SpA has been challenging. Mouse models have been used to gain an understanding of key signaling pathways, cytokines and cells regulating inflammation in these diseases. Biologic therapies directed against these targets have been developed to control both inflammation and effects on bone. Although biologic therapies improve joint inflammation in both RA and SpA, leading to a decrease in pain and improving quality of life for patients, the long-term effects of such therapies must also be evaluated by assessing their impact on structural progression. Inhibition of radiographic progression in both RA and peripheral SpA has been easier to demonstrate than in axial SpA. Here, we discuss the similarities and differences among biologic therapies as they pertain to radiographic progression.
26886128 The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in r 2016 Sep The Gi protein-associated A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells, and this high expression is also reflected in the peripheral blood mononuclear cells of patients with autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. CF101, a selective agonist with high affinity to the A3AR, is known to induce robust anti-inflammatory effect in experimental animal models of adjuvant-, collagen-, and tropomyosin-induced arthritis. The effect is mediated via a definitive molecular mechanism entailing deregulation of the nuclear factor-κB (NF-κB) and the Wnt signal transduction pathways resulting in apoptosis of inflammatory cells. CF101 was found to be safe and well tolerated in all preclinical, phase I, and phase II human clinical studies. In two phase II clinical studies where CF101 was administered to rheumatoid arthritis (RA) patients as a stand-alone drug, a significant anti-rheumatic effect and a direct significant correlation were found between receptor expression at baseline and patients' response to the drug, suggesting that A3AR may be utilized as a predictive biomarker. The A3AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients' response to CF101. This is a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population.
26168847 Applying refinement to the use of mice and rats in rheumatoid arthritis research. 2015 Aug Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat 'models' of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research.
25903069 Human leukocyte antigen polymorphisms and personalized medicine for rheumatoid arthritis. 2015 Nov Human leukocyte antigen (HLA) polymorphisms are the most important genetic risk factors for rheumatoid arthritis (RA), a chronic systemic inflammatory disease of unknown etiology. Certain HLA-DRB1 alleles, known as shared epitope (SE) alleles because they have the same amino-acid sequence at positions 70-74, are associated with susceptibility to RA. A gene dosage effect is present for RA-predisposing SE alleles, and protective alleles show epistasis. An important role of amino-acid polymorphisms at positions 11 and 13 of the HLA-DRβ chain was also reported recently. Rheumatoid factor and anticitrullinated peptide antibodies are present in many RA patients. Similar to extra-articular manifestations, the presence of these autoantibodies is also associated with certain DRB1 alleles. Different frequencies of RA risk alleles in different ethnicities explain the varying prevalence of RA in different populations and suggest genetic heterogeneity of RA with regard to phenotype and population subsets. Some drug-induced hypersensitivity reactions due to disease-modifying antirheumatic drugs are also associated with HLA alleles. Understanding the role of HLA as the most important genetic factor relevant to RA susceptibility may help in determining its pathogenesis and pave the way to personalized medicine.
27365455 The effectiveness of home hand exercise programmes in rheumatoid arthritis: a systematic r 2016 Sep INTRODUCTION: Rheumatoid arthritis (RA) commonly reduces hand function. We systematically reviewed trials to investigate effects of home hand exercise programmes on hand symptoms and function in RA. SOURCES OF DATA: We searched: Medline (1946-), AMED, CINAHL, Physiotherapy Evidence Database, OT Seeker, the Cochrane Library, ISI Web of Science from inception to January 2016. AREAS OF AGREEMENT: Nineteen trials were evaluated. Only three were randomized controlled trials with a low risk of bias (n = 665). Significant short-term improvements occurred in hand function, pain and grip strength, with long-term improvements in hand and upper limb function and pinch strength. AREAS OF CONTROVERSY: Heterogeneity of outcome measures meant meta-analysis was not possible. GROWING POINTS: Evaluation of low and moderate risk of bias trials indicated high-intensity home hand exercise programmes led to better short-term outcomes than low-intensity programmes. Such programmes are cost-effective. AREAS TIMELY FOR DEVELOPING RESEARCH: Further research is required to evaluate methods of helping people with RA maintain long-term home hand exercise.
27547242 Clinical practice guidelines for the foot and ankle in rheumatoid arthritis: a critical ap 2016 BACKGROUND: Clinical practice guidelines are recommendations systematically developed to assist clinical decision-making and inform healthcare. In current rheumatoid arthritis (RA) guidelines, management of the foot and ankle is under-represented and the quality of recommendation is uncertain. This study aimed to identify and critically appraise clinical practice guidelines for foot and ankle management in RA. METHODS: Guidelines were identified electronically and through hand searching. Search terms 'rheumatoid arthritis', 'clinical practice guidelines' and related synonyms were used. Critical appraisal and quality rating were conducted using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: Twenty-four guidelines were included. Five guidelines were high quality and recommended for use. Five high quality and seven low quality guidelines were recommended for use with modifications. Seven guidelines were low quality and not recommended for use. Five early and twelve established RA guidelines were recommended for use. Only two guidelines were foot and ankle specific. Five recommendation domains were identified in both early and established RA guidelines. These were multidisciplinary team care, foot healthcare access, foot health assessment/review, orthoses/insoles/splints, and therapeutic footwear. Established RA guidelines also had an 'other foot care treatments' domain. CONCLUSIONS: Foot and ankle management for RA features in many clinical practice guidelines recommended for use. Unfortunately, supporting evidence in the guidelines is low quality. Agreement levels are predominantly 'expert opinion' or 'good clinical practice'. More research investigating foot and ankle management for RA is needed prior to inclusion in clinical practice guidelines.
26946202 Effect of nonsurgical periodontal treatment in patients with periodontitis and rheumatoid 2016 May 1 BACKGROUND: Periodontitis has been regarded as a potential risk factor for rheumatoid arthrosis (RA). A systematic review is made to determine whether nonsurgical periodontal treatment in patients with RA offers benefits in terms of the clinical activity and inflammatory markers of the disease. MATERIAL AND METHODS: A search was made of the Medline-PubMed, Cochrane, Embase and Scopus databases to identify studies on the relationship between the two disease processes, and especially on the effects of nonsurgical treatment in patients of this kind. The search was based on the following keywords: rheumatoid arthritis AND periodontitis (MeSH), rheumatoid arthritis AND periodontal treatment. RESULTS: Eight articles on the nonsurgical treatment of patients with periodontitis and RA were finally included in the study. All of them evaluated clinical (DAS28) and laboratory test activity (ESR, CRP, IL-6, TNFα) before and after treatment. A clear decrease in DAS28 score and ESR was recorded, while other parameters such as CRP, IL-6 and TNFα showed a nonsignificant tendency to decrease as a result of treatment. CONCLUSIONS: Nonsurgical treatment improved the periodontal condition of patients with periodontitis and RA, with beneficial effects upon the clinical and laboratory test parameters (DAS28 and ESR), while other inflammatory markers showed a marked tendency to decrease. However, all the studies included in the review involved small samples sizes and follow-up periods of no more than 6 months. Larger and particularly longitudinal studies are therefore needed to more firmly establish possible significant relations between the two disease processes.
25854158 [B cell therapy of rheumatoid arthritis with rituximab. Practice-relevant aspects for the 2015 Apr BACKGROUND: B cells play a key role in the pathogenesis of various rheumatic autoimmune diseases and have therefore become an important therapeutic target. Rituximab is a chimeric monoclonal anti-CD20 antibody that induces a nearly complete, transient depletion of peripheral CD20-positive B cells. In 2006 rituximab received approval for use in patients with rheumatoid arthritis (RA) and in 2013 for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). OBJECTIVES: In this review various clinically relevant aspects of B cell therapy in RA patients are discussed, including its role in the therapeutic algorithm as well as data on long-term efficacy and safety.
26869316 Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthriti 2016 Jun 1 Rapid advances in genotyping technology, analytical methods, and the establishment of large cohorts for population genetic studies have resulted in a large new body of information about the genetic basis of human rheumatoid arthritis (RA). Improved understanding of the root pathogenesis of the disease holds the promise of improved diagnostic and prognostic tools based upon this information. In this review, we summarize the nature of new genetic findings in human RA, including susceptibility loci and gene-gene and gene-environment interactions, as well as genetic loci associated with sub-groups of patients and those associated with response to therapy. Possible uses of these data are discussed, such as prediction of disease risk as well as personalized therapy and prediction of therapeutic response and risk of adverse events. While these applications are largely not refined to the point of clinical utility in RA, it seems likely that multi-parameter datasets including genetic, clinical, and biomarker data will be employed in the future care of RA patients.
26697769 Cardiovascular disease in rheumatoid arthritis: Current perspectives on assessing and miti 2015 Aug That individuals with rheumatoid arthritis (RA) have, on average, higher rates of events related to atherosclerotic vascular disease is now well documented and accepted. However, optimal ways to identify RA patients with atherosclerosis, and treat them to mitigate cardiovascular disease (CVD) risk have not been rigorously established. As such, current guidelines for CVD screening and prevention lack an evidence base. In the context of the current understanding of the determinants of atherosclerosis in RA and the current guidelines that have been published, this review focuses on strategies for identifying RA patients at risk of CVD events, and the possible primary and secondary prevention strategies that may be effective.
30351686 Clinical, laboratory and ultrasound thanges in early manifestations of rheumatoid arthriti 2016 Complex analysis of changes in clinical, laboratory and ultrasound manifestations in rheumatoid arthritis revealed relationships between the pathologic process activity, the disease duration, its X-ray stage and ultrasound signs. Manifestation of rheumatoid arthritis is characterized by predominant proliferation and exudation in soft tissues inside joints, tendopathies, chondral plate alterations as hyaline destruction. Articular cartilage erosions can be seen even in 2.8 months after destructive arthritis manifestation. Diagnostic criteria of early rheumatoid arthritis are: articular disorders location, articular syndrome variant (mono-, oligo- and polyarthritic; seropositiveness on rheumatoid factor andACCP), chondral plate state according to ultrasound examination.
26079957 Genetic and genomic markers of anti-TNF treatment response in rheumatoid arthritis. 2015 Despite the success of anti-TNF drugs in the treatment of rheumatoid arthritis, a significant rate of nonresponse remains. Current clinical factors confer little power for predicting response and, in current practice, an unsatisfactory 'trial and error' approach governs therapeutic decisions. Candidate gene and unbiased genome-wide investigations have sought to identify genetic biomarkers that predict who will respond to anti-TNF drugs before the drug is administered. To date, few studies have yielded robust associations; herein, we discuss currently identified associations and the issues that need to be addressed in future investigations including insufficient power and an inadequate measure of disease activity. The potential for alternative predictors of anti-TNF therapy response from transcriptomic and epigenetic data will also be explored.
26397428 An Integrative Review of Correlates and Predictors of Depression in Patients with Rheumato 2015 Oct Depression creates an additional burden for adults with rheumatoid arthritis (RA), negatively affecting disease outcomes and quality of life. An integrative literature review of twenty-three quantitative studies was conducted on correlates and factors predictive of depression in adults with RA. Methodological assessment tools were used to independently evaluate the data quality by two reviewers. Prevalence rates ranged from 6.6 to 66.25%. Correlates included pain, functional status, disease duration, and RA treatment. Predictors, including sociodemographics, pain, coping ability, support, functional status, and clinical factors, varied depending upon the sample, standardized measure, and geographic location. Understanding correlates/predictors could guide the development of comprehensive care.
25630235 Type I IFNs as biomarkers in rheumatoid arthritis: towards disease profiling and personali 2015 Apr RA (rheumatoid arthritis) is a chronic rheumatic condition hallmarked by joint inflammation and destruction by self-reactive immune responses. Clinical management of RA patients is often hampered by its heterogeneous nature in both clinical presentation and outcome, thereby highlighting the need for new predictive biomarkers. In this sense, several studies have recently revealed a role for type I IFNs (interferons), mainly IFNα, in the pathogenesis of a subset of RA patients. Genetic variants associated with the type I IFN pathway have been linked with RA development, as well as with clinical features. Moreover, a role for IFNα as a trigger for RA development has also been described. Additionally, a type I IFN signature has been associated with the early diagnosis of RA and clinical outcome prediction in patients undergoing biological drug treatment, two challenging issues for decision-making in the clinical setting. Moreover, these cytokines have been related to endothelial damage and vascular repair failure in different autoimmune disorders. Therefore, together with chronic inflammation and disease features, they could probably account for the increased cardiovascular disease morbidity and mortality of these patients. The main aim of the present review is to provide recent evidence supporting a role for type I IFNs in the immunopathology of RA, as well as to analyse their possible role as biomarkers for disease management.
27043155 Emerging aspects of molecular biomarkers for diagnosis, prognosis and treatment response i 2016 Jun Important advances have occurred during the last decade in the understanding of the pathogenesis of rheumatoid arthritis (RA). However, we are still far from having a clear picture of the molecular network that predisposes an individual to develop the disease, to worsen the symptoms after that, or to successfully respond to a specific treatment. In this sense, different -omics fields (including transcriptomics, proteomics, metabolomics, genomics and epigenomics) have recently produced promising insights that could definitively help us to sharpen such picture if integrated trough a systems biology approach. In this review we will summarise and discuss the recent progress achieved in those fields and its possible impact on the discovery of suitable biomarkers for RA diagnosis, prognosis and treatment response.
27507661 Association between rheumatoid arthritis and systemic mastocytosis: a case report and lite 2016 Oct Classically, mast cells (MC) are considered as important actors of the innate immune response playing a pivotal role in IgE-mediated allergic and antiparasite responses. In the last two decades, many experimental evidences demonstrated that these hematopoietic-derived cells present in both connective and mucosal tissues are also key modulators of the adaptive immune response and could contribute to autoimmune disease notably in rheumatoid arthritis (RA). Recently, Bader-Meunier et al. reported a series of 31 patients suffering from inflammatory joint diseases associated with mastocytosis, suggesting that mastocytosis was associated with a higher prevalence in spondyloarthritis. We discuss here the possible link between chronic inflammatory arthritis and mastocytosis through the report of a clinical case describing a patient developing RA after a long history of mastocytosis. Of great interest, antihistamine treatment alone was sufficient to treat RA in this patient.
27992285 Are gene polymorphisms related to treatment outcomes of methotrexate in patients with rheu 2017 Jan AIM: Identifying the predictors of responsiveness and adverse events in methotrexate (MTX) treated patients with rheumatoid arthritis (RA) has been the focus of most concern, but still without consistent consensus. METHODS: PubMed and OVID EMBASE were searched to collect relevant studies that addressed correlations between gene polymorphisms and efficacy and/or toxicity in MTX-treated RA patients. Allelic, recessive, dominant and over-dominant model were applied. RESULTS: A total of 68 studies were included. For associations with efficacy, AMPD1 34C>T polymorphism was related to responsiveness in dominant model (odds ratio [OR]: 1.77; 95% CI: 1.19-2.63) and over-dominant model (OR: 1.59; 95% CI: 1.04-2.45). ATIC T675C polymorphism had association with responsiveness in recessive model (OR: 2.54; 95% CI: 1.23-5.26). For associations with toxicity, polymorphisms in TYMS 1494 del6 and FPGS rs10106 were correlated to absenting overall adverse events in recessive model (OR: 0.68; 95% CI: 0.49-0.95) and dominant model (OR: 0.54; 95% CI: 0.35-0.83) respectively while MTHFR C677T was associated with presenting overall adverse events in allelic model (OR: 1.29; 95% CI: 1.02-1.63), recessive model (OR: 1.38; 95% CI: 1.00-1.89) and dominant model (OR: 1.41; 95% CI: 1.02-1.94). CONCLUSION: Polymorphisms in AMPD1 34C>T and ATIC T675C predict responsiveness. The absence of TYMS 1494 del6 and FPGS rs10106 and presence of MTHFR C677T predict adverse events in RA patients treated with MTX. Moreover, variations of the associations were found between Caucasians and non-Caucasians.