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ID PMID Title PublicationDate abstract
19336867 Rheumatoid arthritis and periodontitis: biological links and the emergence of dual purpose 2009 Jan Rheumatoid arthritis and periodontitis are widely prevalent diseases and are characterized by tissue destruction due to chronic inflammation. Recently, there is growing evidence that the two diseases share many pathological features. This article reviews their clinical and biological links. However, there are only a limited number of studies in this area, which prevent us from offering clear evidence.
19233046 Progression in early rheumatoid arthritis. 2009 Feb Rheumatoid arthritis (RA) is a very heterogeneous disease, the outcome of which is difficult to predict. The vast majority of the patients will have disease progression with bone erosions and cartilage breakdown resulting in joint destruction, functional impairment, and increased mortality. The management of RA to prevent and control disease progression has changed considerably in the past few years. The treatment goal should now be to achieve clinical remission in order to prevent structural damage and long-term disability. A very early use of effective disease-modifying anti-rheumatic drugs (DMARDs) is a key point in patients at risk of developing persistent and erosive arthritis. Intensive treatment such as combination DMARDs plus steroids or mainly biological therapies can induce high rates of remission and control of radiological progression, and can provide better outcomes than DMARD monotherapy in early RA, and should be considered very early in at-risk patients. In addition, close monitoring of disease activity and radiographic progression is mandatory in order to adapt DMARD therapy and strategy if necessary.
20969557 Rheumatoid arthritis classification criteria - It's finally time to move on! 2010 The diagnosis of rheumatoid arthritis (RA) is often challenging, due to a wide spectrum of presentations, progressive changes in disease course over time, and, perhaps, most importantly, lack of a clinical or laboratory gold standard to define the presence or absence of disease. Several attempts at the creation of RA classification criteria have been undertaken; however, each time, there have been significant limitations in applying these criteria to the clinical setting. Several components of the 1987 RA criteria require the presence of established joint damage; thus, they were limited in their ability to identify patients with early disease, potentially delaying initiation of early aggressive therapy until irreversible damage had occurred. With the recognition that early, aggressive therapy has the potential to decrease RA-associated morbidity and significantly alter disease course, there is clearly a need for criteria that also will facilitate early diagnosis and encourage initiation of therapy through disease modifying drugs (DMARDs). This mission recently has been taken on by a combined task force composed of membership from both the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), the outcomes of which are discussed below.
19772832 The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. 2009 Oct Interleukin (IL)-17 (also known as IL-17A), the signature cytokine of the newly described T helper 17 (Th17) cell population, has been implicated in the pathogenesis of numerous autoimmune diseases including rheumatoid arthritis. IL-17 is the founding member of a new subclass of cytokines that have highly proinflammatory properties. Studies in rodents and mammalian cell culture systems, as well as clinical settings, support a role for IL-17 in promoting rheumatoid arthritis. This article discusses the history of the discovery of Th17 cells, the potential mechanisms of action of IL-17 in autoimmunity, and perspectives for IL-17-targeted cytokine therapy.
19509330 Unmet needs in rheumatoid arthritis. 2009 Jun Despite recent advances in the treatment of rheumatoid arthritis (RA), including the introduction of biologic therapies and employment of combination disease-modifying antirheumatic drug (DMARD) strategies, remission rates remain suboptimal and patients with RA are still missing a significant number of work days. Early diagnostic criteria are needed to ensure that appropriate treatment is initiated early so as to prevent joint damage. Better prognostic markers are also needed to identify patients with the potential for poor outcomes, in whom more aggressive strategies can be applied at the outset. Because of stringent inclusion criteria and heterogeneous definitions of remission, results seen in clinical trials of RA are not necessarily generalizable to results seen in clinical practice. As a result, existing guidelines may not adequately reflect current practice. In the absence of biomarkers to predict the course of disease, methotrexate remains the standard of care initially for most patients with RA. The ability to predict the course of disease could allow more appropriately targeted therapy and higher rates of remission.
19171111 Antiphospholipid antibodies in rheumatoid arthritis: identifying the dominoes. 2009 Feb Antiphospholipid antibodies (aPL) occur in a variety of autoimmune, malignant, and infectious diseases, with or without the thrombotic or obstetric sequelae that characterize the antiphospholipid syndrome. Although many studies have focused on the clinical implications of aPL in systemic lupus erythematosus, few have specifically addressed the questions facing rheumatologists caring for rheumatoid arthritis patients who are concomitantly positive for aPL. Such a clinical scenario requires current knowledge of antiphospholipid syndrome diagnosis criteria, test reliability, conditions causing temporal positivity of aPL, and treatment risks and benefits. Recently researched factors possibly integral to rheumatoid arthritis's increased morbidity and mortality and related to aPL include oxidatively modified low-density lipoprotein antibodies, homocysteine, annexins, infectious agents, beta estradiol, and specific gene polymorphisms. This review presents current scientific research addressing the pathophysiologic mechanisms and clinical implications of aPL in rheumatoid arthritis.
20205662 Pharmacogenetics in treatment of rheumatoid arthritis. 2010 Over the last decades important progress is being made regarding disease modifying anti-rheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA). Nevertheless, a substantial part of the patients fail to achieve a good response and/or experience toxicity, which limits further treatment leading to progression of inflammation and destruction of joints. These high interindividual differences in drug response gave rise to the need for prognostic markers in order to individualize and optimize therapy with these antirheumatic agents. Besides demographic and clinical factors, studies in the research field of pharmacogenetics have reported potential markers associated with clinical response on treatment with methotrexate and TNF inhibitors. However, publicized conflicting results and underlying interpretation difficulties inhibit drawing definitive conclusions. Presently, clinical implementation of pharmacogenetics as an important step for individualizing drug therapy in RA is not feasible yet. Replication and prospective validation in large patient cohorts are required before pharmacogenetics can be used in clinical practice. This review provides the current state of art in genotyping RA patients as a potential guide for clinical decision making.
19328245 Prospective new biological therapies for rheumatoid arthritis. 2009 Dec Advances in the current knowledge of pathogenetic mechanisms of rheumatoid arthritis have contributed to the development of biological therapy, and translated research findings into clinical practice. TNF-alpha (infliximab, etanercept, adalimumab), IL-1 (anakinra) and IL-6 (tocilizumab) inhibitors, a B-cell depleting agent (rituximab) and a drug blocking T-cell costimulation (abatacept) have been approved for rheumatoid arthritis. The progress in manufacturing biotechnology has contributed to the development of several other prospective agents that may form the basis for the therapy of rheumatoid arthritis in the near future. New or modified TNF-alpha inhibitors (golimumab, certolizumab pegol), new monoclonal antibodies against other cytokines (e.g. IL-1, IL-6, IL-12, IL-15, IL-17, IL-23), and other agents targeting B-cell depletion (e.g. ocrelizumab, ofatumumab) are in various stages of development. Many pharmaceutical companies have focused on developing small molecule inhibitors with possible peroral administration, which are considered promising drugs for rheumatoid arthritis. In most cases, these small molecules inhibit cellular kinases (e.g. p38, JAK or Syk) that mediate the signaling and transcription of proinflammatory genes. In this review, we describe the cytokine inhibitors and modulators of the immune response currently in ongoing clinical trials, the results of which may further expand the spectrum of efficient therapies for chronic autoimmune diseases.
19393192 Cardiovascular risk in rheumatoid arthritis. 2009 Jul The increased mortality in rheumatoid arthritis (RA) is mainly due to (atherosclerotic) cardiovascular disease. The cardiovascular morbidity is also increased in comparison with the general population. This increased cardiovascular burden could be caused by 1) an enhanced prevalence of cardiovascular risk factors 2) under treatment of cardiovascular risk factors or 3) RA itself, particularly due to its chronic inflammatory component. Cardiovascular risk factors only partially explain the increased cardiovascular risk and it is becoming increasingly acknowledged that the underlying inflammation in RA plays an essential role. This is probably related to the fact that atherosclerosis also has an inflammatory etiology that is accelerated by RA. Similarly, it can be expected that effective suppression of this inflammatory process by disease modifying antirheumatic drugs and/or biologicals lowers the cardiovascular risk. Altogether, there is accumulating evidence that the increased cardiovascular risk in RA is comparable to that of type 2 diabetes and actually RA should be seen as a new, independent, cardiovascular risk factor for which cardiovascular risk management is essential.
20354048 Recent advances in rheumatoid arthritis. 2010 Apr Management of rheumatoid arthritis (RA) has radically changed over the last decade. Diagnostic methods have improved with availability of highly specific tests such as antibody to cyclic citrullinated peptide (specificity approximately 96%), and introduction of advanced imaging modalities such as ultrasound and magnetic resonance imaging to facilitate earlier diagnosis. The current aim of management is to achieve remission and prevent joint damage. In order to achieve this goal, inflammation is suppressed as much as possible during the early phase of the disease before onset of joint damage. Aggressive treatments with combinations of disease modifying anti-rheumatic drugs are commenced earlier in the course of disease, and tight control maintained with regular objective monitoring of disease activity. Early use of anti-TNFalpha (tumour necrosis factor alpha) therapy in combination with methotrexate helps to achieve better clinical and radiographic outcomes, which can be maintained for up to 5 years after withdrawal of anti-TNFalpha therapy. Apart from anti-TNFalpha, several other biological treatments are now available, including those that target CD20 on B cells (rituximab), cytokines such as IL1 (anakinra) and IL6 (tocilizumab), and molecules that cause interaction between antigen presenting cells and T cells (abatacept). There is better awareness and understanding of RA associated complications such as cardiovascular disease and osteoporosis. Use of non-steroidal anti-inflammatory drugs is on the decline in light of recent concerns about cardiovascular safety. Evidence is emerging in support of statins and bisphosphonates for improving RA disease activity and preventing erosions, respectively. In the coming years, further improvements in therapeutic strategies are likely with the pace at which research is currently progressing.
19342954 Long-term outcomes of rheumatoid arthritis. 2009 May PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is recognized as a disease with a natural history of severe long-term outcomes, which appear to be improving at this time, as reported from many clinics. RECENT FINDINGS: Improved outcomes of many long-term consequences of inflammation such as joint deformity, functional declines, work disability, and early death have been reported in recent years. SUMMARY: Therapies for RA are assessed in randomized clinical trials and in clinical care primarily according to measures of inflammatory activity, which may change considerably over days, weeks, and months. In usual clinical care, long-term consequences of the disease, which often require years of observation, can also be assessed. Data in published reports of both clinical trials and clinical care continue to include only a minority of all patients with RA. Further efforts are needed to promote collection of quantitative data in all patients with RA, at all visits in all clinical settings, to facilitate 'tight control' and better outcomes for all patients with RA.
19932198 Profiling of rheumatoid arthritis associated autoantibodies. 2010 Apr An increasing number of rheumatoid arthritis (RA)-associated autoantibodies (AAB) are available for AAB profiling that may improve the early diagnosis of RA and provide prognostic and, probably theranostic information. To select AAB specificities for optimal AAB combinations, known AAB should be evaluated with standardized methods by means of standardized study designs and subjected to statistical analysis. Profiling of anti-citrullinated peptide/protein antibodies (ACPA), anti-A2/RA-33 antibodies, and rheumatoid factors (RF) IgM and IgA improves the serologic diagnosis of RA using cut-offs corresponding to 98% specificity for each parameter included. Currently, the combination of anti-CCP antibodies with RF IgM and RF IgA is recommended either in parallel or by stepwise determination. Because anti-CCP antibody demonstrated the best diagnostic performance for profiling, this AAB should be used for first-line screening. The main advantage of AAB profiling is the increased sensitivity for RA diagnosis. Additional benefits of AAB profiles comprise the increased diagnostic specificity of particular AAB combinations (e.g., ACPA plus RF or RF IgM plus RF IgA) and their possible association with disease development and/or therapy response. The inclusion of novel RA-associated AAB (RAAB) and use of clinically evaluated multiplex assays may facilitate the use of profiling in diagnostic routine laboratories.
20368651 Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheuma 2010 Apr 6 BACKGROUND: Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti-citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis. PURPOSE: To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease. DATA SOURCES: 10 medical databases from inception to September 2009, with no language or publication restrictions, and references of included studies. STUDY SELECTION: Two independent reviewers screened searches. Full articles were assessed by one reviewer and checked by a second reviewer to identify studies that reported 2 x 2 data on ACPA for the diagnosis of rheumatoid arthritis (by 1987 American College of Rheumatology criteria). DATA EXTRACTION: One reviewer abstracted data on patient characteristics, ACPA details, and 2 x 2 data and assessed study quality by using the QUADAS tool. A second reviewer checked extractions. DATA SYNTHESIS: 151 studies were included, with considerable heterogeneity in sensitivity (range, 12% to 93%) and specificity (range, 63% to 100%). In cohort studies that investigated second-generation anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with early rheumatoid arthritis (<2 years), summary sensitivity and specificity were 57% (95% CI, 51% to 63%) and 96% (CI, 93% to 97%), respectively. Case-control and cross-sectional studies and studies of patients with established rheumatoid arthritis all overestimated sensitivity. Anti-CCP2 had greater specificity than rheumatoid factor (96% vs. 86%), with similar sensitivity. Evidence was insufficient to ascertain whether the combination of anti-CCP2 and rheumatoid factor provides additional benefit over anti-CCP2 alone. LIMITATIONS: Most studies used a diagnostic case-control design, which overestimated sensitivity. Items relating to study quality were rarely reported. Publication bias could not be assessed. CONCLUSION: Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis.
19772833 The role of biomarkers in the management of patients with rheumatoid arthritis. 2009 Oct In recent years, patient outcomes have improved dramatically with the availability of effective treatments for the management of rheumatoid arthritis (RA). RA, however, is a heterogeneous disease with variable disease progression and treatment response. Whereas some patients respond to a single disease-modifying antirheumatic drug, others require more intensive treatment strategies. Assessing disease severity at diagnosis and monitoring disease activity on an individual level would be a more accurate way of tailoring therapy, ensuring optimal treatment for those at greatest risk of disease progression, long-term disability, and joint damage without unnecessary overtreatment. Assessment of disease activity and severity is currently based on a combination of clinical and laboratory parameters that aid treatment decisions. Use of biomarkers may provide a more accurate means of objectively assessing the disease. This article reviews the role of biomarkers in the management of RA.
19798029 IL-17 as a future therapeutic target for rheumatoid arthritis. 2009 Oct The discovery of interleukin (IL)-17 and its major cell source, the type 17 T-helper (TH17) lymphocyte, has been a major step in the understanding of erosive arthritis. This Review summarizes current knowledge of the role of IL-17 in this context derived from both animal models and studies in patients with rheumatoid arthritis. Evidence shows that IL-17 is present at sites of inflammatory arthritis and that, in synergistic interactions, it amplifies the inflammation induced by other cytokines, primarily tumor necrosis factor. In several animal models of arthritis, inhibition of IL-17 limits inflammation and joint erosion. Initial observations from phase I trials show that signs and symptoms of RA are significantly suppressed following treatment with anti-IL-17 antibodies, without notable adverse effects. The emergence of IL-17 blockade as a future therapy in rheumatoid arthritis is highlighted, along with the potential goals and limitations of this therapeutic approach.
20346251 Prognostic factors for erosive rheumatoid arthritis. 2010 Jan The course of rheumatoid arthritis (RA) varies among patients, ranging from a mild disease with a small impact on patient's functional capacity to a severe, erosive and catastrophic disease accompanied by subluxations, deformities and subsequent poor quality of life. In clinical practice, the prediction of the outcome of RA is substantial in terms of making the right therapeutic decision for each patient. Reliable prognostic factors of long-term outcome are needed, so as to distinguish patients prone to severe disease course from patients with a smaller probability of severe structural damage. For the former group early aggressive treatment is required, whereas in the latter group remission may be achieved with less aggressive and potentially less toxic treatments. In the present review, the predictive role of demographic, clinical, laboratory, imaging, immunological and genetic characteristics of RA patients is discussed.
20851924 Rheumatoid arthritis-interstitial lung disease-associated mortality. 2011 Feb 1 RATIONALE: Mortality rates from rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are largely unknown. OBJECTIVES: We sought to determine mortality rates from rheumatoid arthritis-associated interstitial lung disease in the United States from 1988 through 2004. METHODS: Using data from the National Center for Health Statistics, we calculated age-adjusted mortality rates from the deaths of persons with rheumatoid arthritis-associated interstitial lung disease, determined the prevalence of interstitial lung disease in all decedents with rheumatoid arthritis, and compared the age and underlying cause of death in these two cohorts of decedents. MEASUREMENTS AND MAIN RESULTS: From 1988 to 2004, there were 39,138,394 deaths in U.S. residents and 162,032 rheumatoid arthritis-associated deaths. Of these deaths, 10,725 (6.6%) met criteria for rheumatoid arthritis-associated interstitial lung. Mortality rates from rheumatoid arthritis fell over the course of this study in both women and men. However, mortality rates from rheumatoid arthritis-associated interstitial lung disease increased 28.3% in women (to 3.1 per million persons in 2004) and declined 12.5% in men (to 1.5 per million persons in 2004). Because the rate of decline in rheumatoid arthritis outpaced rheumatoid arthritis-associated interstitial lung disease in men, the prevalence of rheumatoid arthritis-associated interstitial lung disease increased in both sexes over time. CONCLUSIONS: Clinically significant RA-ILD occurs in nearly 10% of the RA population, and is associated with shortened survival and more severe underlying disease. Whereas overall mortality rates for RA have fallen, those associated with RA-ILD have increased significantly in older age groups.
19233047 Cardiovascular co-morbidity in early rheumatoid arthritis. 2009 Feb Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease (CVD), mostly accelerated atherosclerotic CVD, and there is evidence that this occurs early in the inflammatory disease process. Both traditional and novel CVD risk factors as well as the effects of the RA disease process and its treatment interact and contribute to the development of CVD in RA. In this review we discuss the evidence for co-morbid CVD complicating early RA. This includes examining studies of mortality outcome and CVD events in cohorts of early RA patients as well as studies using surrogate markers for atherosclerotic CVD in RA. The evidence for shared risk factors for RA and CVD is presented. Screening and modification of CVD risk factors should be an integral part of care for any patient diagnosed with RA. Novel methods to diagnose CVD in high-risk asymptomatic RA patients need to be evaluated.
19242695 Cutaneous manifestations associated with rheumatoid arthritis. 2009 Jul Rheumatoid arthritis presents various cutaneous manifestations, either specific or nonspecific skin features, which are induced by the activation of inflammatory cells (neutrophils, lymphocytes, macrophages), vasculopathy, vasculitis, acral deformity, drugs, and so on. These include (1) specific findings, (2) findings due to vascular impairment, (3) findings due to immune dysfunction, (4) characteristic neutrophilic conditions, and (5) miscellaneous conditions. On the other hand, some of the specific manifestations show common histopathological features such as palisading granulomas with necrobiosis. It is important to recognize the common and/or uncommon skin conditions of RA for all clinicians associated with RA therapy.
20060506 Neutrophils in rheumatoid arthritis: More than simple final effectors. 2010 Jun Rheumatoid arthritis is the most common inflammatory joint disease. The etiopathogenesis of this condition has been classically explained by a T cell-driven process. However, recent studies have highlighted the possible contribution of neutrophils for the early phases of RA physiopathology. These cells are phagocytic leukocytes that play crucial roles in the acute defense against pathogens while modulating the function of other immune cells and contributing to the perpetuation of an initial inflammatory response. The herein article reviews recent progresses in the understanding of the immunopathology of RA with a special emphasis on the role of neutrophils.