Browse

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

ID PMID Title PublicationDate abstract
29323341 Rheumatoid arthritis in 2017: Protective dietary and hormonal factors brought to light. 2018 Feb Tremendous progress has been made in the identification of rheumatoid arthritis (RA) risk factors in 2017. The results of epidemiologic studies highlighted dietary factors and hormones that are associated with slowing the transition from one preclinical phase of RA to another, potentially protecting individuals from developing RA.
29697434 Evolution of clinical trials for rheumatoid arthritis and spondyloarthritis. 2018 Jul PURPOSE OF REVIEW: The present review presents an overview of the evolution in trial design from mainly randomized placebo-controlled efficacy trials to more strategic clinical trials in rheumatoid arthritis and spondyloarthritis. Additionally, it relates to how these differently designed trials have affected clinical practice. RECENT FINDINGS: Placebo-controlled clinical trials, comparing a new agent to placebo on a stable background, have resulted in the development of a wide array of therapeutic agents in rheumatoid arthritis and spondyloarthritis. However, these kind of trials do have some down sides as they do not provide evidence on the optimal strategy to use this multitude of treatments in daily clinical practice and the ethics concerning a placebo phase are often discussed. These and other concerns resulted in the emergence of various different types of trials in rheumatoid arthritis. A similar change of focus is now observed in spondyloarthritis clinical trials. We address literature on direct comparison ('head-to-head'), noninferiority trials, induction-maintenance, discontinuation, and treat-to-target/tight control clinical trials. SUMMARY: In recent years various clinical trials have been published with a design different from placebo-controlled clinical trials. These novel trial designs aimed to provide guidance on the optimal way to use the full range of targeted treatments available and to make it possible, in some design, to leave out the placebo. In rheumatoid arthritis, some of these more strategic type of trials have had a large impact on common practice. In spondyloarthritis, the first steps toward trials with a more strategic design have been taken, and it stands to reason that more will follow.
29801753 B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti-TNF-α Agents on B Lymphocyt 2018 Jun PURPOSE: The aim of this article was to review published research related to B lymphocytes in rheumatoid arthritis, their role in the pathogenesis of the disease, the effects of tumor necrosis factor (TNF)-α inhibitors on B lymphocytes, the risk for infection, and responses to vaccines. METHODS: A PubMed search was conducted to review recent advances related to B lymphocytes and the effects of anti-TNF-α on B lymphocytes in rheumatoid arthritis. FINDINGS: B lymphocytes play an important role in the pathogenesis of rheumatoid arthritis. In this review, we summarize the major mechanisms by which B lymphocytes play a pathologic role in the development and propagation of the disease, as B lymphocytes are recruited to the synovial fluid, where they contribute to local inflammation through the secretion of pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) and present antigens to T cells. We discuss the effects of TNF-α, either direct or indirect, on B lymphocytes expressing receptors for this cytokine. We also show that total B-cell numbers have been reported to be reduced in the blood of patients with rheumatoid arthritis versus healthy controls, but are significantly increased up to normal levels in patients undergoing anti-TNF-α therapy. As for B-cell subsets, controversial results have been reported, with studies showing decreased frequencies of total memory B cells (and memory subsets) and others showing no differences in patients versus healthy controls. Studies investigating the effects of anti-TNF-α therapy have also given controversial results, with therapy found to increase (or not) the frequency of memory B lymphocytes, in patients with rheumatoid arthritis versus healthy controls. Those highly variable results could have been due to differences in patient characteristics and limited numbers of subjects. Finally, we summarize the effects of blocking TNF-α with anti-TNF-α agents on possible infections that patients with rheumatoid arthritis may contract, as well as on responses to vaccination. IMPLICATIONS: B lymphocytes play a significant role in the pathogenesis of rheumatoid arthritis, and B cell-depletion therapy has a major effect on the course of the disease. The advances in treatment of rheumatoid arthritis include the development of targeted therapies. Anti-TNF-α therapies are widely used despite potentially serious adverse events. The data on the effects of anti-TNF-α therapies on B lymphocytes are limited and conflicting. There is a need for larger studies to better understand the effects of newly discovered therapies on the different cells of the immune system.
28598026 Altered Expression of MicroRNAs in Rheumatoid Arthritis. 2018 Jan Rheumatoid arthritis is one of the most common types of inflammatory joint diseases. Women, smokers, and people with positive family history are more susceptible to this disease. Diagnostic criteria include at least one swollen joint that has not been caused by other diseases. MicroRNAs are non-coding RNAs that are evolutionarily conserved and have a length of 18-25 nucleotides. MicroRNAs control gene expression at the post-transcriptional level via promoting mRNA degradation or translational repression. Recognition of alterations in microRNA status and their respective targets, may offer an opportunity to better identify the pathways that are involved in the etiopathogenesis of autoimmune diseases. It has been suggested that microRNAs may serve as potential biomarkers for both diagnosis and prognosis of autoimmune diseases. Here, we review the available evidence on the deregulations of microRNA expression in rheumatoid arthritis. More precisely, this review focuses on the microRNA involved in T cell regulation and gives perspectives on the use of this microRNA as biomarkers of diagnosis, prognosis, or intervention efficacy. J. Cell. Biochem. 119: 478-487, 2018. © 2017 Wiley Periodicals, Inc.
29468833 Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integrat 2018 May OBJECTIVE: In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning. METHODS: Twenty histologic features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis [OA] patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes. RESULTS: Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C-reactive protein (CRP) levels were significantly correlated with the severity of pain in the high inflammatory subgroup but not in the others. CONCLUSION: Gene expression analysis of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels were used to generate a histologic scoring algorithm in which the histologic scores were found to be associated with parameters of systemic inflammation, including the erythrocyte sedimentation rate, CRP level, and autoantibody levels. Comparison of gene expression patterns to clinical features revealed a potentially clinically important distinction: mechanisms of pain may differ in patients with different synovial subtypes.
30276426 [What is certain in the treatment of rheumatoid arthritis?]. 2018 Dec Rheumatoid arthritis (RA) is the most important chronic inflammatory joint disease with a prevalence of 1%. When untreated the disease leads to joint destruction and therefore to functional restrictions of the patients and also to increased rates of cardiovascular and malignant diseases. After the pathophysiology of rheumatoid arthritis was better understood, in the last 20 years biologics could be developed, which are directed against targets involved in the inflammatory process in RA. Since then the remission rates of RA have substantially increased. In 2017 Janus kinase (JAK) inhibitors were additionally approved for the treatment of RA in Germany. They further broaden the therapeutic options and, in contrast to biologics, are administered orally. The response rates to therapy are better the earlier the disease is diagnosed and treated. Patients in whom RA is suspected due to a new onset of polyarthritis, should therefore be promptly referred to a rheumatologist.
30213700 Mechanistic immunological based classification of rheumatoid arthritis. 2018 Nov The classical autoimmunity paradigm in rheumatoid arthritis (RA) is strongly supported by immunogenetics suggesting follicular helper T-cell responses driving high titre specific autoantibodies that pre-dates disease onset. Using the immunological disease continuum model of inflammation against self with "pure" adaptive and innate immune disease at opposite boundaries, we propose a novel immune mechanistic classification describing the heterogeneity within RA. Mutations or SNPs in autoinflammatory genes including MEFV and NOD2 are linked to seronegative RA phenotypes including some so called palindromic RA cases. However, just as innate and adaptive immunity are closely functionally integrated, some ACPA+ RA cases have superimposed "autoinflammatory" features including abrupt onset attacks, severe attacks, self-limiting attacks, relevant autoinflammatory mutations or SNPs and therapeutic responses to autoinflammatory pathway therapies including colchicine and IL-1 pathway blockade. An emergent feature from this classification that non-destructive RA phenotypes, both innate and adaptive, have disease epicentres situated in the extracapsular tissues. This mixed innate and adaptive immunopathogenesis may be the key to understanding severe disease flares, resistant disease subsets that are unresponsive to standard therapy and for therapies that target the autoinflammatory component of disease that are not currently considered by expert therapeutic recommendations.
28818745 A systematic review on the role of eicosanoid pathways in rheumatoid arthritis. 2018 Mar BACKGROUND: Rheumatoid arthritis is characterized by the production of eicosanoids, cytokines, adhesion molecules, infiltration of T and B lymphocytes in the synovium and oxygen reduction accompanied by the cartilage degradation. Eicosanoids are responsible for the progressive destruction of cartilage and bone, however neither steroids, nor the non steroidal anti-inflammatory drugs (NSAIDs), cannot slow down cartilage and bone destruction providing only symptomatic improvement. The current rheumatoid arthritis treatment options include mainly the use of disease-modifying anti-rheumatic drugs, the corticosteroids, the NSAIDs and biological agents. METHODS: PubMed, Cochrane, and Embase electronic database were used as the main sources for extracting several articles, reviews, original papers in English for further review and analysis on the implication of arachidonic acid metabolites with rheumatoid arthritis and different strategies of targeting arachidonic acid metabolites, different enzymes or receptors for improving the treatment of rheumatoid arthritis patients. RESULTS: We first focused on the role of individual prostaglandins and leukotrienes, in the inflammatory process of arthritis, concluding with an outline of the current clinical situation of rheumatoid arthritis and novel treatment strategies targeting the arachidonic acid pathway. CONCLUSIONS: Extended research is necessary for the development of these novel compounds targeting the eicosanoid pathway, by increasing the levels of anti-inflammatory eicosanoids (PGD(2),15dPGJ(2)), by inhibiting the production of pro-inflammatory eicosanoids (PGE(2), LTB(4), PGI(2)) involved in rheumatoid arthritis or also by developing dual compounds displaying both the COX-2 inhibitor/TP antagonist activity within a single compound.
29627896 Clinical connection between rheumatoid arthritis and liver damage. 2018 May When liver damage is present in rheumatoid arthritis (RA) patients, it is sometimes difficult to determine whether it is a hepatic manifestation of RA, associated primary liver disease or hepatotoxic liver disease which developed during the treatment of RA. Liver damage during RA is most common in the form of asymptomatic abnormal liver tests. Occasionally, liver damage may progress to cirrhosis. Patients with RA are more susceptible to an associated autoimmune liver disease. Medications used in rheumatology are often hepatotoxic and it is difficult to differentiate between hepatic manifestations of the primary disease and potential hepatotoxicity of the administered medications. The significance of the paper is in the fact that it includes the most relevant and the latest information on this commonly present problem in clinical practice. The aim of the author is to provide comprehensive but at the same time concise data which will be useful to the doctors who come into contact with RA patients with symptomatic or asymptomatic liver disease. Timely diagnosis and treatment of liver disease in RA patients can significantly influence the course and outcome of rheumatoid arthritis.
28736274 Biomarkers as a treatment guide in rheumatoid arthritis. 2018 Jan It is anticipated that biomarkers support rheumatologists to judge a group of patients that can improve the diagnosis and prognosis, and further facilitate appropriate and precise treatment with targeted therapy. In particular, biomarkers for predicting and monitoring response to biological disease modifying anti-rheumatic drugs (DMARDs) are demanding. Given the mechanism action of biological DMARDs is much more simple than the conventional synthetic DMARDs, a variety of approaches to find such biomarkers has been taken recent years. In this article, I will summarize the background for biomarker research and introduce recent topics in the research and the possible clinical applications of biomarkers to guide treatment in rheumatoid arthritis (RA).
29108829 TNF inhibitors in rheumatoid arthritis and spondyloarthritis: Are they the same? 2018 Jan The advent of anti-tumour necrosis factor (TNF) drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) has revolutionised the approach to patients with active disease who do not respond to conventional therapy. Although there are differences in their structure, morphology, pharmacokinetic properties and activity, all anti-TNF drugs ultimately neutralise the TNFα pathway of inflammation. However, despite their similar clinical efficacy, there are disagreements concerning drug survival and safety, with systematic reviews and meta-analyses confirming one result or the other. The fact that 20-30% of patients fail to respond to TNFα inhibitors indicates the possibility of primary resistance or the development of an immune response to the drugs themselves, which may act as antigens. The overall benefit of switching to another anti-TNF drug or a biological agent with a different mechanism of action, may be a valuable option in individual patients. There are few data concerning the use of anti-TNF drugs in patients with SpA but it seems that there are fewer adverse advents and higher drug survival in comparison with patients with RA.
30620280 Geriatric syndromes in patients with rheumatoid arthritis: a literature overview. 2019 May Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease of unknown aetiology which principally affects the small joints of the hands and feet. The incidence of RA increases with age and peaks within the age range of 70 to 79 years. In the ageing population, therefore, it is expected that the number of patients with RA will grow proportionally and more patients will have comorbidities but also so-called geriatric syndromes (GS). GS are clinical and multifactorial conditions in older persons that are associated with poor health outcomes, do not fit into disease categories (comorbidities) and require a multidimensional treatment approach. Patients suffering from RA may be at increased risk for GS. Therefore, it is important that rheumatologists are knowledgeable about the constructs represented by GS, understand the main risk factors, and gain insight in how to recognise these syndromes. Limited awareness of the (risk for) GS in patients with RA among rheumatologists may lead to ineffective management of RA. Our objective was to provide a comprehensive overview about the prevalence, aetiologic factors and health consequences of the most important GS in patients with RA.
28757342 Rheumatoid arthritis treated with tocilizumab in two patients with complicated chronic liv 2018 Jan Erosive, active rheumatoid arthritis inpatients with portal hypertension combining esophageal varices and ascites complicating chronic liver disease poses serious management problems. Current literature does not provide any valid therapeutic management. We report the case of a woman and a man aged 52 and 66 years respectively having this combination of pathologies. Infusions of 4mg/kg of tocilizumab as monotherapy have produced a weaning from corticosteroids, both clinical and structural remission, with particular liver safety satisfactory at 10 and 18 months.
30191517 Treating Fatigue in Rheumatoid Arthritis: Does Patient Age Matter? 2018 Oct Clinically relevant fatigue is common in patients with rheumatoid arthritis (RA) and might be expected to be related to patient age and disease severity. This review provides a brief introduction to fatigue as a patient-reported outcome that contributes significantly to burden of disease, with a focus on the evidence in elderly patients, and gives an overview of our current understanding of the factors that contribute to fatigue. We summarize the evidence for the effects of pharmacological (disease-modifying anti-rheumatic drugs, DMARDs) and non-pharmacological interventions for fatigue. The underlying pathophysiology of fatigue is complex and often multifactorial. The experience of fatigue varies between individuals, and subtypes of fatigue are increasingly being recognized. Fatigue can therefore be challenging to recognize and quantify. Recent systematic reviews have shown that fatigue can be improved as a result of treatment with traditional and biological anti-rheumatic drugs, and also with non-pharmacological approaches (physical activity, psychosocial interventions). Age does not appear to be of major importance for fatigue in RA, and similar strategies for treating fatigue apply to all age groups, including the elderly.
29691058 ER Stress: A Therapeutic Target in Rheumatoid Arthritis? 2018 Jul Diverse physiological and pathological conditions that impact on protein folding of the endoplasmic reticulum (ER) cause ER stress. The unfolded protein response (UPR) and the ER-associated degradation (ERAD) pathway are activated to cope with ER stress. In rheumatoid arthritis (RA), inflammation and ER stress work in parallel by driving inflammatory cells to release cytokines that induce chronic ER stress pathways. This chronic ER stress may contribute to the pathogenesis of RA through synoviocyte proliferation and proinflammatory cytokine production. Therefore, ER stress pathways and their constituent elements are attractive targets for RA drug development. In this review, we integrate current knowledge of the contribution of ER stress to the overall pathogenesis of RA, and suggest some therapeutic implications of these discoveries.
29672803 Magnetic Resonance Imaging of Rheumatoid Arthritis: Peripheral Joints and Spine. 2018 Apr Both the fields of rheumatology and radiology are changing rapidly. Effective medication has become available for rheumatoid arthritis (RA) and transformed it from a progressive disabling disease into a chronic disease. Indications for magnetic resonance imaging (MRI) have changed accordingly, shifting toward early detection. There is also an overall increased clinical demand for high-end imaging. Together with improvement of MRI units and sequences, MRI protocols are adapted based on clinical indications. This article addresses (1) the clinical background and present role of MRI in early disease detection, (2) RA involvement of peripheral joints, (3) RA involvement of the spine, and (4) state-of-the-art RA MRI protocols. The key toward cost-effective MRI examination in RA is communication between radiologist and rheumatologist as well as awareness and knowledge of the basics and advancements in both fields.
29204672 Bone Loss in Rheumatoid Arthritis: Basic Mechanisms and Clinical Implications. 2018 May Patients with rheumatoid arthritis (RA) have historically developed progressive damage of articular bone and cartilage, which correlates with disability over time. In addition, these patients are prone to periarticular and systemic bone loss, carrying additional morbidity. In contrast to what is seen in many other rheumatic diseases, the impact of inflammation on bone in RA is uniquely destructive. Loss of articular bone (erosions) and periarticular bone (demineralization) is a result of excessive bone resorption and markedly limited bone formation. There has been tremendous progress in preventing net bone loss in RA with the advent of disease-modifying agents, including biologic agents and small molecules, that both limit inflammation and may have a direct impact on the prevention of cytokine- and antibody-driven osteoclastogenesis. However, repair of existing bone erosions, although feasible, is observed infrequently. Lack of repair is a consequence of suppression of osteoblast function and bone formation by some of the same mechanisms that promote osteoclastogenesis and bone resorption. As new agents are introduced to control inflammation in RA, and novel mechanisms to target synovitis are identified, it may be possible in the future to fully repair damaged bone.
28635309 Rheumatoid arthritis is associated with negatively variable impacts on domains of female s 2018 Jan To systematically review the literature to identify the impact of rheumatoid arthritis (RA) on specific female sexual function domains. A meta-analysis was performed and the related literature were searched in MEDLINE, EMBASE, Cochrane Library, CNKI, CBM and Web of Science databases, and in reference lists of articles and systematic reviews. Score of the Female Sexual Function Index (FSFI) was used as the outcome measurement, and mean differences (MD) with 95% confidence intervals (CI) were calculated. Five studies were included, including 346 women with RA and 237 healthy female controls. Each domain of the FSFI score: lubrication (MD, -2.48; 95% CI, -3.69, -1.28), orgasm-1.71 (-2.09, -1.33), sexual desire-1.27 (-1.59, -0.95), satisfaction-1.67 (-2.18, -1.16), arousal-1.83 (-2.85, -0.82), pain-1.57 (-2.43, -0.70) and the total score -8.84 (-11.88, -5.79) were lower in RA women than healthy controls. Furthermore, lubrication dimension was most severely affected especially. This meta-analysis showed that female RA patients scored lower in each dimension of FSFI, mostly in the lubrication domain. It demonstrated that targeted interventions should be done to improve their sexual function. Future well-designed researches with larger sample sizes are necessary to evaluate the potential risk factors which determine female sexual dysfunction.
30069877 Implications of the noncoding RNAs in rheumatoid arthritis pathogenesis. 2018 Jan Epigenetics refers to a set of regulatory mechanisms that affect gene expression, while the original sequence of the DNA remains unchanged. Because the advance of noncoding RNAs (ncRNAs), the role of microRNAs (miRNAs) has been gradually highlighted in the regulation of numerous cellular processes. A bulk of studies has identified that ncRNAs might be divided into several subtypes. On the one hand, investigations have disclosed the role of these molecules in normal physiological conditions of the cells. On the other hand, there is sufficient evidence that ncRNAs participate in the pathogenesis of diseases. Through this review article, we attempted to gain a comprehensive understanding of the role of ncRNAs, long ncRNAs, miRNAs, and other subtypes in pathogenesis, diagnosis, and treatment of rheumatoid arthritis (RA). Research demonstrated aberrant expression of several miRNAs in various cell and tissue types of patients with RA in comparison to the healthy individuals as well as in animal studies. Furthermore, plausible molecular mechanisms of alterations in ncRNAs expression has been discussed in causing the disease state. These alterations seem promising to be used as biomarkers in RA diagnosis. Alternately, they might be targeted by drugs to interrupt inflammation and other disease complications to treat patients with RA.
30005856 Inflammation and dementia: Using rheumatoid arthritis as a model to develop treatments? 2018 Sep Dementia is a major international public health problem which looks set to grow as the ageing population increases. Despite large amounts of investment there has been relatively little progress in developing new therapies to combat this. There is a growing body of evidence that both local and systemic inflammation are important in dementia; with cerebral inflammation occurring secondarily to beta-amyloid plaques, raised levels of serum inflammatory molecules and cytokines being present in Alzheimer's disease patients and systemic inflammation being associated with cerebral microvasculature disease in vascular dementia. Observational studies had suggested that non-steroidal anti-inflammatory drugs may reduce the risk of dementia, but subsequent interventional studies have been disappointing. More recently some observational studies have suggested a protective effect from conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS) and tumour necrosis factor inhibiting (TNFi) biological therapies. Treatments for inflammatory rheumatic diseases have previously been repurposed and used successfully in other diseases, such as TNFi for inflammatory bowel disease. There are also studies looking at the use of csDMARDs such as methotrexate to improve outcomes after cardiovascular events. Ongoing interventional trials are currently looking at whether therapies designed to treat inflammatory and autoimmune diseases have the potential to be used to treat dementia.