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ID PMID Title PublicationDate abstract
23964304 Rheumatoid arthritis--early diagnosis and disease management. 2013 Jul BACKGROUND: 0.5% to 0.8% of all adults suffer from rheumatoid arthritis (RA). The main considerations for persons with new-onset RA are early diagnosis, disease-modifying anti-rheumatic drugs (DMARDs), remission, and interdisciplinary treatment. METHOD: As part of the process of creating a new S3 guideline on the management of early RA and a new S1 guideline on stage-adapted pharmacotherapy for RA, the authors conducted a selective search and review of the literature and specifically updated it to 20 March 2013. RESULTS: In patients presenting with joint inflammation, the diagnosis of RA can be directly confirmed (positive predictive value, 85% to 97%), and its prognosis assessed, on the basis of the following findings: joint examination, acute phase reaction, serology (rheumatoid factor [RF], antibody against citrullinated peptides/proteins [ACPA], and duration of symptoms (ACR/Eular classification criteria, 2010). Early, remission-oriented and adapted treatment with DMARDs ("treating to target") leads to several years of normal bodily function without disability in 40% to 60% of patients. Treatment by an interdisciplinary team promotes the achievement of this goal. The risks associated with this form of treatment are low, with a dropout rate of less than 1 per 100 patient-years. Life-threatening complications are rare. CONCLUSION: Early diagnosis, intervention with DMARDs in the first three months of disease, and the achievement of a remission minimize the adverse sequelae of RA. The sequential introduction of DMARDs, including biological agents in non-responders, as part of a treat-to-target concept optimizes the long-term outcome, as has been demonstrated in clinical trials for periods of up to eight years.
25427390 [Pathogenesis of rheumatoid arthritis]. 2014 Rheumatoid arthritis (RA) is an autoimmune systemic disease that primarily affects joints. Etiology and the pathogenesis of RA are complex, involving many types of cells, among others macrophages, T and B cells, fibro- blasts, chondrocytes and dendritic cells. Despite well documented role of many genes and epigenetic modifications in the development and evolution of the disease, in most RA patients there is no clear predisposing factor present. Environmental factors involved in RA pathogenesis are cigarette smoke, industrial pollutants like silica crystals, disturbances of intestinal, lung, and oral microbiota and some specific bacterial and viral infectious agents and their components. In the initial disease stage there are qualitative and quantitative disturbances ofpeptide citrulination as well as other protein modifications, followed by antigen presenting cell (APC) (macrophages and dendritic cells) and fibroblast like synoviocytes (FLS) activation. Some microbes foster this processes by APC and FLS direct and indirect activation. In the second stage APC's elicit specific humoral B cell re- sponse resulting in specific antibodies production and T cell autoreactivity. Inherited and acquired defects in T and B cell responses caused by repeated activation of innate immunity as well as loss of tolerance, elicit chronic autoimmune inflammation, primarily of synovial membranes, and development of cellular panus. Pathologic activation of the osteoclasts and release of the immune system effector molecules and the proteolytic enzymes damage the cartilage, bone and tendons composition and structure. Persistent inflammation through its complex mechanisms results in many systemic and extraarticular RA manifestations of almost all organ systems, resulting in severe complications and comorbidities such as rheumatoid lung, carditis, vasculitis, cahexia, anemia, accelerated atherosclerosis, myocardial and cerebrovascular vascular disease, lymphoma, osteoporosis, depression etc. Accumulated complications and comorbidities finally result in handicap, social dysfunction and premature death.
24072602 Epigenetics in rheumatoid arthritis: a primer for rheumatologists. 2013 Nov Epigenetic anomalies are emerging as key pathogenic features of rheumatoid arthritis (RA). The effect of epigenetics in RA ranges from contributing to complex disease mechanisms to identifying biomarkers for early diagnosis and response to therapy. This review focuses on three key epigenetic areas in RA, namely DNA methylation, histone modification, and expression and/or function of microRNAs. Epigenomics studies of DNA methylation have identified alterations of genome-wide DNA methylation in cells from patients with rheumatoid arthritis. Histone modification studies have focused on histone acetylation, which tends to be increased in RA. Preclinical studies show that inhibitors of histone deacetylases are effective in cellular and animal models of RA. Genome-wide and candidate microRNA surveys identified increased or reduced expression of selected microRNAs in rheumatoid arthritis. These microRNA are either pro or anti-inflammatory in multiple cell types or affect osteoclast physiology and the pathogenesis of bone erosion. Defining epigenetic contributions to the pathogenesis of RA, especially in combination with understanding genetic associations, could lead to novel therapy and a clearer understanding of disease risk.
24105334 Rheumatoid arthritis in the elderly in the era of tight control. 2013 Nov The principles of treating rheumatoid arthritis (RA) have changed considerably in recent years. Disease-modifying treatment (if possible, methotrexate) should be started as soon as the diagnosis of RA is made. The purpose of treatment is to achieve remission or, alternatively, low disease activity, and patients should be assessed every 1-3 months if they have early RA in order to achieve this aim. The same principles of treatment should apply in the elderly. However, it is more difficult to assess RA activity in the elderly. Overall disease activity and/or pain may be overestimated, as elderly patients may suffer from other diseases. Conversely, the number of joints with synovitis can be underestimated compared with young patients, and regular ultrasound assessment should therefore be considered. Treatment may be more difficult because of concomitant diseases and the increase in drug-related side effects. The role of corticosteroids is still controversial as their short-term symptomatic effects on clinical activity and potential medium-term effect on structural deterioration are counter-balanced by their side effects. Dosages of methotrexate need to be adjusted for creatinine clearance. The anti-tumor necrosis factors (TNFs) appear to be slightly less effective in the elderly. The frequency of adverse effects of anti-TNFs is higher in an elderly population, although the same is seen with comparator disease-modifying treatments. Limited information is available for rituximab and tocilizumab. Uncertainties remain about the management of RA in the elderly as there have been few studies in this population. The safety of the biotherapies therefore still needs to be confirmed, together with the benefit-risk balance of corticosteroid therapy compared with biological therapy.
23916467 Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD). 2013 Oct Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD.
25437290 Prediction of future rheumatoid arthritis. 2014 Nov Rheumatoid arthritis (RA) results from an interaction between genetic susceptibility and environmental factors. Several of these factors are known, such as family history of RA, high birth weight, smoking, silica exposure, alcohol nonuse, obesity, diabetes mellitus, rheumatoid factor, anti-citrullinated protein antibody, and genetic variants such as the shared epitope and protein tyrosine phosphatase nonreceptor type 22. The impact of these factors can be modeled in the 2 main groups at risk of RA: family members of patients with RA and seropositive persons with or without arthralgia. Current models have the potential to select individuals for preventive strategies.
23998731 Current immunotherapy in rheumatoid arthritis. 2013 Sep Rheumatoid arthritis is a common autoimmune disease primarily manifesting as chronic synovitis, subsequently leading to a change in joint integrity. Progressive disability and systemic complications are strongly associated with a decreased quality of life. To maintain function and health in patients with rheumatoid arthritis, early, aggressive and guided immunosuppressive therapy is required to induce clinical remission. Antirheumatic drugs are capable of controlling synovial inflammation and are therefore named 'disease-modifying antirheumatic drugs' (DMARDs). This article aims to bridge the beginning of DMARD therapy with agents such as methotrexate, leflunomide, sulfasalazine, injectable gold and (hydroxy)chloroquine with biological therapies, and with the new era of kinase inhibitors. Mechanisms of action, as well as advantages and disadvantages of DMARDs, are discussed with respect to the current literature and current recommendations.
23384968 Epigenetic modifications in rheumatoid arthritis, a review. 2013 Jun Rheumatoid arthritis is an autoimmune disease characterized by chronic joint inflammation and progressive destruction of cartilage and bone which leads to ultimately loss of function and pain. Activated synovial fibroblasts are key effector cells in the pathogenesis of rheumatoid arthritis. In the recent years, epigenetic changes including DNA methylation, histone acetylation and other histone modifications were identified that are associated with an intrinsic activation and the aggressive phenotype of these cells. So far, no therapies targeting rheumatoid arthritis synovial fibroblasts exist. This review comprises recent research efforts that propose epigenetic mechanisms behind the activation of rheumatoid arthritis synovial fibroblasts and other cell types.
23466960 Rheumatoid arthritis and cardiovascular disease: an update on treatment issues. 2013 May PURPOSE OF REVIEW: This review examines thresholds for treatment of traditional cardiovascular disease (CVD) risk factors among patients with rheumatoid arthritis (RA) and whether RA-specific treatment modulates cardiovascular risk. RECENT FINDINGS: There are substantial data demonstrating an increased CVD risk among patients with RA. Both traditional CVD risk factors and inflammation contribute to this risk. Recent epidemiologic studies strengthen the case that aggressive immunosuppression with biologic disease-modifying anti-rheumatic drugs (DMARDs), such as tumour necrosis factor (TNF) antagonists, is associated with a reduced risk of CVD events. However, to date, there are no randomized controlled trials published regarding the management of CVD in RA. SUMMARY: Epidemiologic evidence continues to accumulate regarding the relationship between the effects of traditional CVD risk factors and RA-specific treatments on cardiovascular outcomes in RA. The field needs randomized controlled trials to better guide management.
24527481 Rheumatoid arthritis: early treatment with corticosteroids and nonsteroidal anti-inflammat 2014 Feb The family physician plays several important roles in the management of patients with RA by early diagnosis of RA, with initiation of synthetic DMARD therapy, and in long-term follow-up to minimize complications of DMARD therapy and its impact on patient comorbidities. Three recently approved products offer some benefit as adjunctive therapy.
24535556 Emerging immunotherapies for rheumatoid arthritis. 2014 Novel treatments in development for rheumatoid arthritis target 3 broad areas: cytokines, cells, and signaling pathways. Therapies from each domain share common advantages (for example previously demonstrated efficacy, potential long-term immunomodulation, and oral administration respectively) that have stimulated research in each area but also common obstacles to their development. In this review recent progress in each area will be discussed alongside the factors that have impeded their path to clinical use.
23296392 Rheumatoid arthritis in 2012: Progress in RA genetics, pathology and therapy. 2013 Feb Developments in our knowledge of the aetiology and pathogenesis of rheumatoid arthritis continued apace in 2012, and several important new advances were reported in the therapy of this disease. Culminating in the approval of a new therapy in the USA, the year offered new insights for clinicians and fresh hope for patients.
25096602 Strategies to predict rheumatoid arthritis development in at-risk populations. 2016 Jan The development of RA is conceived as a multiple hit process and the more hits that are acquired, the greater the risk of developing clinically apparent RA. Several at-risk phases have been described, including the presence of genetic and environmental factors, RA-related autoantibodies and biomarkers and symptoms. Intervention in these preclinical phases may be more effective compared with intervention in the clinical phase. One prerequisite for preventive strategies is the ability to estimate an individual's risk adequately. This review evaluates the ability to predict the risk of RA in the various preclinical stages. Present data suggest that a combination of genetic and environmental factors is helpful to identify persons at high risk of RA among first-degree relatives. Furthermore, a combination of symptoms, antibody characteristics and environmental factors has been shown to be relevant for risk prediction in seropositive arthralgia patients. Large prospective studies are needed to validate and improve risk prediction in preclinical disease stages.
23588519 Ultrasonography in rheumatoid arthritis: what rheumatologists should know. 2013 Feb Ultrasonography has recently gained prestige as an adjuvant method for the diagnosis and therapeutic follow-up of rheumatoid arthritis, although radiography remains the imaging modality traditionally and widely used for those purposes. The great advantage of the ultrasonographic study, which has motivated enthusiastic research in the area, resides in its capacity to detect synovitis and bone erosion at a pre-radiographic phase, which has been increasingly valued in preventing late and definitive structural damage. Because that is a relatively new subject, several scientific articles have been published in recent years about the potential applications of ultrasonography in individuals with rheumatoid arthritis, some of which directed to researchers and others to clinical rheumatologists. This study aimed at assessing the currently available bibliography on the subject and at describing only the concepts that are of practical applicability in the daily routine of clinical rheumatologists.
24268008 Cardiovascular disease in rheumatoid arthritis. 2014 Feb RA can manifest in a variety of cardiac complications, including pericarditis, valvular disease, cardiomyopathy, and amyloidosis. Subclinical involvement is higher than anticipated. CVD is also prevalent in patients with RA, with onset in early disease. Several disease-specific risk factors, like seropositivity, disease activity, and medications, are implicated in the pathogenesis of CVD in RA. Cardiovascular risk assessment in RA varies from the general population. Some traditional risk factors like BMI and lipid levels apply differently to the RA population. Statins are useful in managing dyslipidemia in RA. There is good evidence to support cardiovascular risk reduction with methotrexate and TNF-I use if good disease control is achieved.
23961678 [Arthroscopic synovectomy for rheumatoid arthritis]. 2013 Jul Even though the paradigm shift was occurred in treatments for rheumatoid arthritis (RA), some patients are not well controlled with several treatments. Because arthroscopic techniques advanced remarkably, effectiveness of arthroscopic synovectomy is reconsidered, especially for residual synovitis in biologics unresponders. A combined therapy with biologics and arthroscopic synovectomy leads to improvement of composite measures such as DAS28. Arthroscopic synovectomy can be a powerful tool for the tight control in RA treatments. In addition with progressions of ultrasonography, ultrasound-guided regional anesthesia became popular recently. Using this technique, we can expand indication of surgical intervention even in patients with severe lung problems.
24880190 Cardiovascular risk in rheumatoid arthritis. 2014 Jul The objectives of this review are to discuss data on the cardiovascular risk increase associated with rheumatoid arthritis (RA), the effects of RA treatments on the cardiovascular risk level, and the management of cardiovascular risk factors in patients with RA. Overall, the risk of cardiovascular disease is increased 2-fold in RA patients compared to the general population, due to the combined effects of RA and conventional risk factors. There is some evidence that the cardiovascular risk increase associated with nonsteroidal anti-inflammatory drug therapy may be smaller in RA patients than in the general population. Glucocorticoid therapy increases the cardiovascular risk in proportion to both the current dose and the cumulative dose. Methotrexate and TNFα antagonists diminish cardiovascular morbidity and mortality rates. The management of dyslipidemia remains suboptimal. Risk equations may perform poorly in RA patients even when corrected using the multiplication factors suggested by the EUropean League Against Rheumatism (EULAR) (multiply the score by 1.5 when two of the following three criteria are met: disease duration longer than 10 years, presence of rheumatoid factor or anti-cyclic citrullinated peptide (CCP) antibodies, and extraarticular manifestations). Doppler ultrasonography of the carotid arteries in patients at moderate cardiovascular risk may allow a more aggressive approach to dyslipidemia management via reclassification into the high-risk category of patients with an intima-media thickness greater than 0.9 mm or atheroma plaque.
25366935 Economics of stratified medicine in rheumatoid arthritis. 2014 Dec Clinically relevant examples of stratified medicine are available for patients with rheumatoid arthritis (RA). The aim of this study was to understand the current economic evidence for stratified medicine in RA. Two systematic reviews were conducted to identify: (1) all economic evaluations of stratified treatments for rheumatoid arthritis, or those which have used a subgroup analysis, and (2) all stated preference studies of treatments for rheumatoid arthritis. Ten economic evaluations of stratified treatments for RA, 38 economic evaluations including with a subgroup analysis and eight stated preference studies were identified. There was some evidence to support that stratified approaches to treating a patient with RA may be cost-effective. However, there remain key gaps in the economic evidence base needed to support the introduction of stratified medicine in RA into healthcare systems and considerable uncertainty about how proposed stratified approaches will impact future patient preferences, outcomes and costs when used in routine practice.
24663108 Fertility and infertility in rheumatoid arthritis. 2014 May PURPOSE OF REVIEW: Despite decades of evidence suggesting that women with rheumatoid arthritis (RA) have fewer children than their healthy peers, this information is not widely known among clinicians. The causes of decreased fertility in this population have been largely unexplored, but likely revolve around altered inflammation, increased age when conception is attempted, limited sexual function, and possibly medications limiting ovarian function. RECENT FINDINGS: Several large Scandinavian cohorts and a cohort study in the United States demonstrate that women with RA have smaller families and are slower to conceive compared with other women. Personal choice to limit family size plays some role, as does infertility. Sexual function in women with RA is hampered by pain and fatigue, perhaps decreasing the opportunity for conception. Finally, data about the role of NSAIDs in preventing ovulation suggest that continued use of these medications may hinder conception. SUMMARY: Infertility in women with RA is an under-recognized, but remarkably common phenomenon. Although research continues into the underlying causes, physicians can discuss this topic and refer women to reproductive endocrinology when needed, thereby helping patients to build the families that they desire.
23574518 Rheumatoid arthritis: a clinical overview of new diagnostic and treatment approaches. 2013 Rheumatoid arthritis (RA) is the most frequent form of chronic polyarthritis, affecting 0.5-1% of adults worldwide. In recent years there have been important advances in the pathogenesis of RA, together with new diagnostic and therapeutic insights. Early diagnosis is essential in order to prevent joint damage and improve the prognosis and quality of life of patients with RA. New classification diagnostic criteria have been proposed to achieve this objective. New therapeutic strategies have proved to be effective, including early and better use of synthetic disease-modifying anti-rheumatic drugs (DMARDS), mainly methotrexate, and a treat-to-target strategy focusing on achieving remission and with tight control of the disease. In the last decade, the introduction of various biological agents in the therapeutic armamentarium of RA has changed the disease prognosis, although no definite cure is currently possible. In this chapter, we present an overview of recent advances in the epidemiology, diagnosis, prognosis and treatment of this severe but treatable disease.