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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
24961616 The effect of antidrug antibodies on the sustainable efficacy of biologic therapies in rhe 2014 Aug Biologic therapies, predominantly TNF-α inhibitors, have revolutionized the treatment of rheumatoid arthritis (RA). However, their clinical utility can be limited by the development of antidrug antibodies (ADAs). Immunogenicity is a complex phenomenon related to various drug, disease, and patient characteristics, and may be more common with the monoclonal antibodies than with etanercept, a soluble TNF receptor-Fc immunoglobulin fusion protein. Neutralizing antibodies - those that hinder bioactivity by preventing drug molecules from binding to TNF - are correlated with reduced serum drug concentrations, loss of therapeutic response, adverse events, and treatment discontinuation. Cost-effective use of these agents will depend on further research into drug and ADA assays, and how they should guide dose reduction or switching strategies.
24715196 The effectiveness of working wrist splints in adults with rheumatoid arthritis: a mixed me 2014 Jun OBJECTIVE: To evaluate the effectiveness of working wrist splints in people with rheumatoid arthritis. DATA SOURCES AND STUDY SELECTION: This review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Ten databases were searched from inception until September 2012 for quantitative and qualitative studies on the effectiveness of working wrist splints in rheumatoid arthritis. DATA EXTRACTION: Data was extracted on participants, interventions, outcome measures and results. Experimental studies were evaluated using the van Tulder scale and the Cochrane Risk of Bias tool. Data was extracted by a single reviewer and all studies were reviewed by two blind reviewers. DATA SYNTHESIS: Twenty-three studies were included in the review (n = 1,492), 13 experimental studies including 9 randomized controlled trials (RCTs) and 2 qualitative studies. Data was summarized using best evidence synthesis and a meta-ethnographical approach guided qualitative evidence synthesis. There is strong quantitative evidence (including 9 RCTs), supported by conclusions from qualitative literature, that working wrist splints reduce pain (d = 0.7-0.8), moderate evidence that grip strength is improved (d = 0.3-0.4) and dexterity impaired and insufficient evidence of their effect on function. CONCLUSIONS: Working wrist splints reduce pain and improve grip in rheumatoid arthritis. The effect of splints on function is not yet clear.
23236191 The temporal relationship between depression and rheumatoid arthritis disease activity, tr 2013 Oct OBJECTIVE: To determine whether depression has a temporal association with RA disease activity, treatment persistence and response to therapy. METHODS: We performed a systematic review encompassing an electronic database search of all published literature since the availability of biologic response modifiers (beginning in 1998) investigating the impact of depression on downstream RA disease progression and treatment. RESULTS: Only seven articles that evaluated temporal relationships between depression and RA outcomes comprising disease activity, treatment persistence and response to therapy, were included in the review. Results from these studies suggest that depression may exacerbate pain and disease activity and decrease the efficacy of pharmacological (i.e. biologic and non-biologic DMARDs) and some non-pharmacological (e.g. cognitive behavioural therapy) RA treatments. CONCLUSION: Given the available evidence, depression probably has a temporal influence on RA disease progression and treatment. However, it is unclear whether these observed effects are due to a response tendency on patient-reported outcomes created from negative cognitive perceptions, immunologically mediated processes that increase inflammation or behavioural changes that lead to decreased physical activity and a greater sensitivity to pain.
23745516 Mixed treatment comparison of efficacy and tolerability of biologic agents in patients wit 2013 Oct OBJECTIVE: To determine the comparative efficacy and tolerability of abatacept and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional disease modifying anti-rheumatic drugs (DMARDs). RESEARCH DESIGN AND METHODS: A systematic review identified RCTs in RA patients who responded inadequately to conventional DMARDs and were treated with one of the following biologic agents: abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, or golimumab. Bayesian hierarchical models were used to compare efficacy and tolerability outcomes of abatacept and combined TNFi at 6 months and 1 year. RESULTS: In this mixed treatment comparison (MTC), the likelihood of achieving ACR response was comparable between abatacept and combined TNFi at 6 months for ACR20, 50, and 70: (odds ratio [OR] = 0.98 [95% confidence interval (CI): 0.73, 1.27], 0.99 [0.73, 1.31], and 0.91 [0.62, 1.27], respectively); and at 12 months for ACR20 (OR = 1.27 [0.92, 1.71]) and ACR50 (1.21 [0.82, 1.68]), with a higher likelihood of achieving an ACR70 response at 12 months (1.41 [1.02, 1.82]). Odds of DAS28 remission at 12 months was greater for abatacept than the combined TNFi (OR = 2.03 [1.04, 3.58]). Abatacept had better tolerability, defined as a lower likelihood of withdrawal due to adverse events, at both 6 and 12 months (OR = 0.38 [0.10, 0.88] and 0.51 [0.27, 0.86], respectively). These analyses include indirect comparisons across clinical trials and are not a replacement for head-to-head data. While all TNFi have been grouped into one class, there may be some differences between the individual TNFi that are not captured in our study. CONCLUSIONS: In this MTC, abatacept demonstrated similar efficacy at 6 months, a higher likelihood of achieving ACR70 response and DAS28 remission at 12 months and better tolerability relative to the combined TNFi in patients with RA who had an inadequate response to conventional DMARDs.
23492742 The new European League Against Rheumatism/American College of Rheumatology diagnostic cri 2013 May PURPOSE OF REVIEW: This era of early aggressive treatment of rheumatoid arthritis (RA) calls for criteria that allow timely classification of patients at risk of persistent erosive disease. We review how the new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria meet up to this challenge. RECENT FINDINGS: The new 2010 ACR/EULAR classification criteria for RA were developed using initiation of methotrexate as anchor in a population with undifferentiated arthritis. Many studies from different countries have now been published that have addressed the performances of these new criteria. SUMMARY: The goal of earlier classification of RA seems to be met with the new criteria, but exclusion of other diagnoses is essential. Increased sensitivity comes at the price of loss of specificity and indiscriminate use of these classification criteria as a diagnostic tool carries the risk of overtreatment.
23584368 The role of high mobility group box chromosomal protein 1 in rheumatoid arthritis. 2013 Oct High mobility group box chromosomal protein 1 (HMGB1) is a ubiquitous highly conserved single polypeptide in all mammal eukaryotic cells. HMGB1 exists mainly within the nucleus and acts as a DNA chaperone. When passively released from necrotic cells or actively secreted into the extracellular milieu in response to appropriate signal stimulation, HMGB1 binds to related cell signal transduction receptors, such as RAGE, TLR2, TLR4 and TLR9, and becomes a proinflammatory cytokine that participates in the development and progression of many diseases, such as arthritis, acute lung injury, graft rejection immune response, ischaemia reperfusion injury and autoimmune liver damage. Only a small amount of HMGB1 release occurs during apoptosis, which undergoes oxidative modification on Cys106 and delivers tolerogenic signals to suppress immune activity. This review focuses on the important role of HMGB1 in the pathogenesis of RA, mainly manifested as the aberrant expression of HMGB1 in the serum, SF and synovial tissues; overexpression of signal transduction receptors; abnormal regulation of osteoclastogenesis and bone remodelling leading to the destruction of cartilage and bones. Intervention with HMGB1 may ameliorate the pathogenic conditions and attenuate disease progression of RA. Therefore administration of an HMGB1 inhibitor may represent a promising clinical approach for the treatment of RA.
24744505 Could biomarkers of bone, cartilage or synovium turnover be used for relapse prediction in 2014 OBJECTIVE: The aim of this review is to clarify the usefulness of bone, cartilage, and synovial biomarker in the management of rheumatoid arthritis (RA) therapy in remission. SYNOVIAL BIOMARKERS: High MMP-3 levels are associated with joint progression in RA patients, but there is no data about their utility in clinical remission. IIINys and Glc-Gal-PYD seem to be more specific to synovium, but more studies are required. CARTILAGE BIOMARKERS: Unbalance between cartilage break-down biomarkers (urinary CTX II and COMP) and cartilage formation biomarker (PIIANP) was described. This unbalance is also associated with joint destruction and prognosis of destruction. No data are available on patients in remission. BONE BIOMARKERS: RA activity is correlated with an increase of bone resorption markers such as CTX I, PYD, and TRACP 5b and a decrease of bone formation markers such as OC and BALP. RA therapies seem to improve bone turnover in limiting bone resorption. There is no study about bone marker utility in remission. CONCLUSION: Biomarkers seem to correlate with RA activity and progression. They also could be used to manage RA therapies, but we need more data on RA remission to predict relapse.
23378540 EULAR definition of erosive disease in light of the 2010 ACR/EULAR rheumatoid arthritis cl 2013 Apr The aim of this report was to propose a definition for erosive disease in the context of inflammatory arthritis in light of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) criteria for use in clinical practice and studies. A EULAR task force was formed including 16 rheumatologists and one rheumatology fellow. The process was both evidence based and consensus based, and included, between March 2010 and April 2012, analyses of data from two cohorts, two face-to-face meetings, one online voting and one teleconference. The Leiden Early Arthritis Cohort and the French ESPOIR cohort were used for the evidence-based part. The outcome measures, which were initiation of methotrexate therapy, or any disease-modifying antirheumatic drug therapy within the first year of disease and arthritis persistency over 5 years, were studied with the aim to give the best definition of erosive disease. A decision was made to select a definition with a high specificity and focus on patients who did not otherwise fulfil the 2010 ACR/EULAR RA criteria (<6 points). By a unanimous vote the following definition was selected: erosive disease for use in the 2010 ACR/EULAR RA classification criteria is defined when an erosion (defined as a cortical break) is seen in at least three separate joints at any of the following sites: the proximal interphalangeal, the metacarpophalangeal, the wrist (counted as one joint) and the metatarsophalangeal joints on radiographs of both hands and feet. A highly specific definition for erosive disease has thus been formulated.
23961659 [Pathological mechanisms in rheumatoid arthritis]. 2013 Jul Rheumatoid arthritis(RA) is a representative autoimmune disease characterized by systemic, chronic, destructive inflammatory synovitis and multiple organ manifestations, resulting in severe disability and mortality rates. Immune cells such as T cells, B cells, dendritic cells and macrophages and cellular interaction among them through cytokines and cell surface molecules plays a pivotal role in the pathological processes of RA. The accumulation of inflammatory cells, the self-perpetuation of inflammation and induction and/or activation of osteoclasts lead to cartilage and bone destruction and multiple organ manifestations. The importance of immune systems in the pathogenesis of RA has become apparent based on the clinical efficacy of biologic agents TNF, IL-6, CD28 and CD20. The research translation between bench and bedside would bring enormous progress in the treatment of RA.
24620997 Challenges and opportunities in the early diagnosis and optimal management of rheumatoid a 2015 Mar Early diagnosis and early initiation of disease-modifying antirheumatic drug (DMARD) therapy slow the progression of joint damage and decrease the morbidity and mortality associated with rheumatoid arthritis (RA). According to the European League Against Rheumatism (EULAR) guidelines, treatment should be initiated with methotrexate and addition of biological DMARDs such as tumour necrosis factor (TNF) inhibitors should be considered for RA patients who respond insufficiently to methotrexate and/or other synthetic DMARDs and have poor prognostic factors. Africa and the Middle East is a large geographical region with varying treatment practices and standards of care in RA. Existing data show that patients with RA in the region are often diagnosed late, present with active disease and often do not receive DMARDs early in the course of the disease. In this review, we discuss the value of early diagnosis and remission-targeted treatment for limiting joint damage and improving disease outcomes in RA, and the challenges in adopting these strategies in Africa and the Middle East. In addition, we propose an action plan to improve the overall long-term outlook for RA patients in the region.
23774408 Inter- relationship between rheumatoid arthritis and periodontitis. 2013 Jan BACKGROUND: Periodontal medicine defines a rapidly emerging branch of Periodontology focusing on establishing a strong relationship between periodontal health and systemic health. It is speculated that the major common dysregulation which links Periodontitis with Rheumatoid arthritis (RA) is being played by the mediators of immune inflammatory response. OBJECTIVES: To determine whether there is any relationship between periodontal disease and Rheumatoid arthritis. METHODS: A total of 100 patients were included for the present study which was divided into two groups: one group (cases) included 50 patients attending the Department of Orthopedics, Kasturba Medical College, Manipal who were diagnosed of Rheumatoid arthritis. Another subject population included 50 patients as controls attending the Department of Oral Medicine, Manipal College of Dental Sciences, Manipal with age and gender matched with those of rheumatoid arthritis group. Specific measures for periodontitis included plaque index, gingival index, number of missing teeth, and radiographic alveolar bone loss scores. Measures of rheumatoid arthritis included health assessment questionaires, levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Various periodontal parameters were compared between the cases and controls. RESULTS: The average alveolar bone loss was statistically more severe in Rheumatoid arthritis (RA) group than in the controls although there were similar plaque index in both the groups. The gingival index was statistically higher in the RA group. The Erythrocyte Sedimentation Rate (ESR) and C- Reactive Protein (CRP) levels of RA patients were also significantly associated with the severity of periodontal disease. CONCLUSION: There was a significant association between Rheumatoid arthritis and Periodontitis which may be due to a common underlying deregulation of the inflammatory response in these individuals.
25427391 [Clinical approach to a patient with rheumatoid arthritis]. 2014 Rheumatoid arthritis (RA) is chronic inflammatory rheumatic disease which leads to joint damage, functional im- pairment and reduced quality of life. The disease should be recognized early when there is a "window of oppor- tunity" to apply adequate treatment which may prevent structural damage. As clinical presentation of RA is not always typical, great knowledge and clinical experience, including collaboration of rheumatologist, general practi- tioner and patient, are required. The treatment should be started immediately upon the diagnosis, while the choice of modality of treatment depends on the rheumatologist in accordance with the patient. The RA patients with the higher risk of aggressive disease need to be recognized because they require more aggressive treatment from the start. The goal of the treatment is remission or at least low disease activity. Current treatment of RA includes disease modifying antirheumatic drugs (DMARDs) synthetics and biologics, nonsteroidal antirheumatic drugs (NSAIDs), glucocorticoids, analgesics, and rarely cytostatics. The course of disease is usually fluctuating with the exchange of relapses and remissions. Recognition of the relapsing patient on time enables treatment intensification or modifications in treatment scheme. Special issue in RA represents glucocorticoid-induced osteoporosis (GIO) which should be prevented by usage of calcium and vitamin D supplements and treated by antiresorptive or osteoanabolic agents. Besides the treatment of the primary disease, the care of RA patients should consider comorbidities, side effects of treatment, complications of disease, and psychosocial aspects of chronic disease.
24873878 Arthritis susceptibility and the gut microbiome. 2014 Nov 17 Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though both genetic and environmental factors have been suggested to be involved in its pathogenesis. While infections and other environmental factors (e.g. smoking) have been studied extensively and show some association, a direct link between all the factors has been difficult to prove. With the recent advances in technology, it has become possible to sequence the commensals that are residing in our gut. The gut microbiome may provide the missing link to this puzzle and help solve the mystery of many leaky gut syndromes. The gut commensals are involved in maintaining host immune homeostasis and function suggesting that they might be critical in altering the immune system, which leads to autoimmune diseases like RA. Mouse models support the role of the gut microbiota in predisposition to RA. If that is true, the power of gut-derived commensal can be harnessed to our benefit by generating a biomarker profile along with genetic factors to define individuals at risk and by altering the gut microbial composition using various means.
24219037 Efficacy and safety of methotrexate in combination with other non-biologic disease-modifyi 2013 Methotrexate (MTX) is well-established as the "anchor drug" for patients with rheumatoid arthritis (RA), to be used early and aggressively, with higher long-term effectiveness, tolerability, and safety than any other disease-modifying antirheumatic drug (DMARD). However, about 20% to 40% of patients experience incomplete responses to MTX and require further therapy, with options including other non- biologic DMARDs, low dose glucocorticoids, and biologic agents. Non-biologic DMARDs in combination with MTX may provide similar efficacy to a biologic agent in clinical trials, with fewer adverse events and lower costs. This re- view presents a summary of 21 clinical trials documenting the efficacy and safety of MTX in combination with other non-biologic DMARDs.
23961660 [Genetic analyses of rheumatoid arthritis]. 2013 Jul The etiology of rheumatoid arthritis (RA) is unknown and genetic information is important for understanding the mechanisms of the disorder. In order to identify diseases-associated genes, genome wide association study (GWAS) has been performed. Through GWAS, many RA associated genes have been reported. Several genes are related to T cell differentiation, signaling in the immune cells, innate immunity and TNF signaling. Some of these polymorphisms are shared by several autoimmune diseases. On the other hands, it is important to know that there are ethnic differences in these autoimmune related genes. We reported functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with RA. We also identified an RA associated polymorphism in the promoter region of FCRL3, a member of the Fc receptor-like family. Through these studies, we believe that we could obtain further insights into the disease mechanisms, develop novel therapies and make personalized medicine possible based on the individual's genetics.
23385088 New advances of microRNAs in the pathogenesis of rheumatoid arthritis, with a focus on the 2013 May Rheumatoid arthritis (RA) is a symmetrical polyarticular disease of unknown aetiology that affects primarily the articular cartilage and bone. Characteristic features of RA pathogenesis are persistent inflammation, synovium hyperplasia and cartilage erosion accompanied by joint swelling and joint destruction. Several lines of evidence have showed a crucial role of activated fibroblast-like synoviocytes (FLS) in the pathogenesis of RA. MicroRNAs (miRNAs) are endogenous, single-stranded, non-coding RNAs with about 21 nucleotides in length and have been detected in a variety of sources, including tissues, serum, and other body fluids, such as saliva. In light of key roles of miRNAs in the regulation of gene expression, miRNAs influence a wide range of physiological and pathological processes. For example, miRNAs are evident in various malignant and nonmalignant diseases, and accumulating evidence also shows that miRNAs have important roles in the pathogenesis of RA. It has been demonstrated that miRNAs can be aberrantly expressed even in the different stages of RA progression, allowing miRNAs to help understand the pathogenesis of the disease, to act as important biomarkers, and to monitor the disease severity and the effects of drug treatment. In addition, miRNAs are emerging as potential targets for new therapeutic strategies of this kind of autoimmune disorders. The ultimate goal is the identification of miRNA targets that could be manipulated through specific therapies, aiming at activation or inhibition of specific miRNAs responsible for the RA development. In this review, the importance of miRNAs in the pathogenesis of RA is discussed systematically, with particular emphasis on the role of the crosstalk between DNA methylation and the microRNA machinery.
23777823 Modulating the co-stimulatory signal for T cell activation in rheumatoid arthritis: could 2014 Jan Advances in our understanding of the key mediators of chronic inflammation and tissue damage in rheumatoid arthritis (RA) have fostered the development of targeted therapies and greatly expanded the available treatment options. Abatacept, a soluble human fusion protein that selectively modulates the co-stimulatory signal required for full T-cell activation, is approved for the treatment of moderate to severe RA in the United States, Canada, and the European Union. This review summarises the data on efficacy (disease activity, quality of life, prevention of structural damage) and safety from randomised clinical trials of abatacept plus methotrexate in patients with: i) active RA and an inadequate response to methotrexate who are naïve to biological disease-modifying anti-rheumatic drugs; and ii) methotrexate-naïve early RA with poor prognostic factors. Novel imaging outcomes and biological changes induced by abatacept treatment are also briefly reviewed. Optimal use of abatacept as a first-line biological therapy is discussed in light of the current recommendations and guidelines.
25468920 Rheumatoid arthritis: from palliation to remission in two decades. 2014 Dec The last 20 years have seen a transformation in the landscape of rheumatoid arthritis, which has changed from being a life limiting condition to a chronic but often remitting illness. The importance of early disease control, the better use of existing therapies, and the development of new therapies have all been key to this success. The future of therapy now lies in the identification of stratifying biomarkers, to allow more rational delivery of treatment. The ultimate goal remains the reintroduction of immune tolerance to potentially achieve a 'cure.'
25157371 Cardiovascular disease risk amongst African black patients with rheumatoid arthritis: the 2014 Rheumatoid arthritis (RA) enhances the risk of cardiovascular disease to a similar extent as diabetes. Whereas atherogenesis remains poorly elucidated in RA, traditional and nontraditional risk factors associate similarly and additively with CVD in RA. Current recommendations on CVD risk stratification reportedly have important limitations. Further, reported data on CVD and its risk factors derive mostly from data obtained in the developed world. An earlier epidemiological health transition is intrinsic to persons living in rural areas and those undergoing urbanization. It is therefore conceivable that optimal CVD risk stratification differs amongst patients with RA from developing populations compared to those from developed populations. Herein, we briefly describe current CVD and its risk factor profiles in the African black population at large. Against this background, we review reported data on CVD risk and its potential stratification amongst African black compared to white patients with RA. Routinely assessed traditional and nontraditional CVD risk factors were consistently and independently related to atherosclerosis in African white but not black patients with RA. Circulating concentrations of novel CVD risk biomarkers including interleukin-6 and interleukin-5 adipokines were mostly similarly associated with both endothelial activation and atherosclerosis amongst African black and white RA patients.
24528339 [Importance of nutritional treatment in the inflammatory process of rheumatoid arthritis p 2014 Feb 1 INTRODUCTION: Clinical characteristics of rheumatoid arthritis (AR) justify its multidisciplinary approach, within which nutritional intervention is included. Certain nutritional components influence the cellular metabolism and interfere in the pathological inflammatory process, so that they may act as coadjutant in the treatment of many inflammatory diseases, among which AR is in - cluded. AIM: To analyze the evidence related to the therapeutical effects of the polyunsaturated fatty acids, mediterranean diet, olive oil and certain antioxidant nutrients, on chronic inflammation and AR symptomatology. METHODS: Non-Systematic revision in Cochrane, Pubmed, Scopus, Sportdiscus and Amed, from 2003 to March 2013, and subsequent applications of inclusion and exclusion criteria. RESULTS: Evidence on polyunsaturated fatty acids suggests that they produce clinical improvement and inhibitory effects over the AR inflammatory response. As regards the mediterranean diet, evidence points out that it decreases both pain and disease activity. In the case of the olive oil, although there are not enough studies, some effects are observed such as inflammatory markers reduction and oxidative stress inhibition. Finally, limited and contradictory evidence is found regarding the effectiveness of antioxidants. CONCLUSION: There exist studies which suggest that some dietetic elements (polyunsaturated fatty acids, mediterranean diet and antioxidants) have anti-inflammatory effects and decrease AR disease activity. More studies are required to empower the results on those aspects where evidence is still non conclusive.