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ID PMID Title PublicationDate abstract
20697983 Remission in rheumatoid arthritis. 2010 Oct With advancing therapeutic options, achieving a state of remission has become the treatment goal in rheumatoid arthritis. Agreeing on what constitutes remission and what measures should be used to assess disease activity has remained a challenge. Multiple remission criteria have been devised and modified, all with different strengths and limitations. A consensus definition of remission will need to be achieved if we are to be able to evaluate outcomes of clinical trials and establish treatment targets for practice. Remission defined as the complete absence of disease currently may not be a realistic therapeutic goal.
19648945 Is rheumatoid arthritis really getting less severe? 2009 Aug The incidence of rheumatoid arthritis (RA) is decreasing, and rheumatologists perceive that their patients are presenting with less-disabling disease. This impression coincides with the availability of improved therapeutic options, including biologic agents. In RA, the term 'disease severity' can be defined from various perspectives: that of the patient, or by measures of disease activity and damage. This Perspectives article examines the scientific basis for a perceived decrease in RA severity over time, as determined by patient-reported outcomes and measures of disease severity and structural damage. An improved health care system and better treatment strategies with access to new therapeutic modalities are likely to have contributed to a milder RA disease course in more-recent years. The focus needs to be kept on these issues to further improve disease severity in patients with RA.
19772830 Rheumatoid arthritis genetics: 2009 update. 2009 Oct Recent human genetic discoveries have increased our understanding of rheumatoid arthritis (RA) susceptibility. Genome-wide association studies have expanded the number of validated RA risk loci beyond HLA-DRB1 "shared epitope" alleles to include additional major histocompatibility complex (MHC) risk alleles and more than 10 regions outside the MHC. The newly discovered risk alleles are common in the general population, have a modest effect on RA risk, and together explain less than 5% of the variance in disease risk. Whereas the actual causal mutation and causal gene for most loci remain to be determined, these studies are beginning to reveal general themes: many risk loci are associated with other autoimmune diseases; many genes fall within discrete biological pathways (eg, the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway); and human genetics can group diseases into clinically meaningful subset categories (eg, presence or absence of autoantibodies). This review discusses recent RA genetic discoveries in terms of their potential to improve patient care.
19148656 [Rheumatoid arthritis. Target outcome for treatment]. 2009 Feb Rheumatoid arthritis is a chronic disabling disease that results in considerable loss of physical function in patients over time. The ultimate goal of therapy is remission, a clinical state with a highly variable definition in the literature. For the purpose of achieving the best patient outcome, it is important to maintain the lowest possible disease activity. Therefore, stringent remission criteria should be chosen, which will lead to the best possible prevention of structural and functional decline. Standardised intensive therapeutic strategies and algorithms should form the basis for the administration of anti-rheumatic medication.
20652573 [Stress and rheumatoid arthritis]. 2010 Aug Rheumatoid arthritis (RA) is a chronic rheumatic disease of unknown aetiology and variable severity. It is now well known that several risk factors are involved in its pathogenesis, including genetic factors and sex hormones as well as environmental factors, i.e. infections and stress. In particular stress is now recognised as an important risk factor for the onset and even more for the modulation of disease activity in RA. Many studies have clearly shown that chronic mild stress (family or professional stress) may lead to proinflammatory effects, increasing disease activity. Furthermore, a positive correlation between the stress level at the onset of RA and radiological progression could be demonstrated. The onset of RA was associated with moderate stress at work, underlining the possible interactions between the various stress systems and the immune system. In this respect it could be demonstrated that coping strategies reduce stress episodes and change stress management with a positive impact on disease activity in RA. However, more studies are warranted to further explore the pathophysiological implications of stress on onset and activity of chronic autoimmune diseases.
19339921 Early inflammatory arthritis versus rheumatoid arthritis. 2009 Mar PURPOSE OF REVIEW: Rheumatoid arthritis (RA) has started to be perceived as a potentially curable condition with early, aggressive use of disease-modifying antirheumatic drugs. We review the pathophysiological concepts of RA development, the technological advances used to estimate the individual risk of progression to RA, and the impact of antirheumatic therapy for patients presenting with early inflammatory arthritis. RECENT FINDINGS: The finding of a strong gene-environment interaction has modified our concepts of RA pathogenesis and opened new opportunities for disease prevention and therapeutic interventions. Anticyclic citrullinated antibodies and prediction rules have improved our ability to estimate the risk of progression to RA in individual patients presenting with early inflammatory arthritis. In patients at high risk of developing RA, results from trials suggest that treating these patients with potent antirheumatic therapies may slow the progression from early inflammatory arthritis to definite RA and inhibit the progression of joint damage. SUMMARY: Early inflammatory arthritis is a critical period of the disease, during which therapy may have a durable effect and change the natural course of the condition. Physicians need to assess the individual risk of progression to RA in patients presenting with early inflammatory arthritis and consider initiating early disease-modifying antirheumatic drug therapy in patients at high risk of developing RA.
19395871 Pathogenesis of rheumatoid arthritis and c-Fos/AP-1. 2009 May 15 c-Fos/AP-1 controls the expression of inflammatory cytokines and matrix-degrading matrix metalloproteinases (MMPs) important in arthritis via promoter AP-1 binding motif. Among inflammatory cytokines, IL-1beta is the most important inducer of a variety of MMPs, and mainly responsible for cartilage breakdown and osteoclastogenesis. IL-1beta and c-Fos/AP-1 influence each other's gene expression and activity, resulting in an orchestrated cross-talk that is crucial to arthritic joint destruction, where TNFalpha can act synergistically with them. While how to stop the degradation of bone and cartilage, i.e., to control MMP, has long been the central issue in the research of rheumatoid arthritis (RA), selective inhibition of c-Fos/AP-1 does resolve arthritic joint destruction. Thus, the blockade of IL-1beta and/or c-Fos/AP-1 can be promising as an effective therapy for rheumatoid joint destruction in addition to the currently available TNFalpha blocking agents that act mainly on arthritis.
20429843 Rheumatoid arthritis therapy: advances from bench to bedside. 2010 Nov Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with significant functional disability and morbidity. Treatment with conventional disease-modifying anti-rheumatic drugs has substantial limitations including partial efficacy and poor tolerability. Advances in our understanding of the pathogenesis of RA over the past decade have fostered development of targeted therapies and greatly expanded the available treatment options. Several of the therapeutic targets identified by recent studies have been translated into effective therapeutic agents, and many additional agents are currently under active development. In this article, we review the biologic agents that have made successful transitions from bench to bedside as well as the biologic and small molecule agents that are at various stages of development in human trials.
18987647 Rheumatoid arthritis: a view of the current genetic landscape. 2009 Mar The field of genetics and autoimmune diseases is undergoing a rapid and unprecedented expansion with new genetic findings being reported at an astounding pace. It is now clear that multiple genes contribute to each of the major autoimmune disorders, with significant genetic overlaps among them. Rheumatoid arthritis (RA) is no exception to this, and emerging data are beginning to reveal the outlines of new diagnostic subgroups, complex overlapping relationships with other autoimmune disorders and potential new targets for therapy. This review describes the evolving genetic landscape of RA, with the full knowledge that our current view is far from complete. However, with the first round of genome-wide association scans now completed, it is reasonable to begin to take stock of the direction in which the major common genetic risk factors are leading us.
19966683 Rheumatoid arthritis: the role of early intervention and self-management. 2009 Oct 2009 has seen the publication of a number of key documents relating to the care of people with rheumatoid arthritis (RA). The National Institute of Health and Clinical Excellence issued guidance on the management of RA in adults while the King's Fund and National Audit Office have reported on the services that are available for people with RA. This paper will provide an overview of these reports and their implications for primary care. The role of early identification, referral and diagnosis will be explained as well as the treatment options available. The role of self-management and how community nurses can facilitate self-management will be discussed.
20645137 Epidemiology of rheumatoid arthritis: rheumatoid arthritis and mortality. 2010 Oct Increased mortality in rheumatoid arthritis (RA) is widely recognized but not fully explained. Despite substantial improvements in management and growing knowledge of the determinants of increased mortality, evidence for reduction in mortality in RA has lagged behind. Indeed, most studies report no apparent reduction in mortality in RA. However, emerging evidence from some recent RA inception cohorts suggests no increased mortality, including cardiovascular mortality, but this awaits further confirmation. Although it is possible that recent advances in RA treatment may manifest in improvement of survival in the near future, other factors, including undertreated or unrecognized low-grade inflammation, comorbidities, and immunogenetic factors, may contribute to the excess mortality in RA and impede its improvement. In this review, we summarize the current knowledge of the rates and determinants of mortality in RA, identify and discuss potential explanations for excess mortality, and outline promising research avenues for targeting mortality in RA.
19913641 The heart in rheumatoid arthritis. 2010 Apr Morbidity and mortality rates are higher in rheumatoid arthritis (RA) patients than in the general population. Many studies have shown that coronary artery disease is one of the most common causes of death in RA and seems to occur at a younger age than in the general population. RA per se is as much a cardiovascular (CV) risk factor as diabetes, arterial hypertension and dyslipidemia etc., and so it is necessary to plan a follow-up using the same diagnostic and therapeutic approaches as those commonly used for primary and secondary prevention in non-RA patients at high CV risk. All of the cardiac structures can be affected during the course of RA (valves, the conduction system, the myocardium, endocardium and pericardium, and the coronary arteries), and cardiac complications include a variety of clinical manifestations. As these are all associated with an unfavourable prognosis, it is essential to detect subclinical cardiac involvement in still asymptomatic RA patients in order to assure adequate long-term treatment.
19554393 Rheumatoid arthritis is linked to oral bacteria: etiological association. 2009 The purpose of this review is to evaluate the association between rheumatoid arthritis (RA) and periodontopathic bacteria. Clinical studies of RA and periodontal disease have provided evidence for a significant association between the two disorders. Patients with long-standing active RA have a substantially increased frequency of periodontal disease compared with that among healthy subjects. High levels of oral anaerobic bacterial antibodies have been found in the serum and synovial fluid of RA patients. Porphyromonas gingivalis, Tannerella forsythensis, and Prevotella intermedia have been identified in RA synovial fluid. Ornidazole, levofloxacin, and clarithromycin are used in the treatment of infections caused by anaerobic bacteria. These antibiotics have been shown to be effective against RA. The evidence in this review indicates that oral bacteria directly associate with etiopathogenesis of RA.
20534369 Prevention and cure of rheumatoid arthritis: is it possible? 2010 Jun Advances in treatment of rheumatoid arthritis have made it possible to profoundly influence signs and symptoms as well as the course of joint destruction in inflammatory arthritis. Earlier and more efficient treatment appears to significantly improve the prognosis of this disease. Despite these advances, cure (the absence of signs and symptoms without further treatment) is still relatively rare, observable in, at most, 20% of the patients. Remission (or a state of very low disease activity), however, has been observed with intense and individually tailored treatment in up to 75% of patients. The use of structured assessments followed by individual modification of the intensity of treatment aiming for remission leads to better clinical responses and radiological outcomes. It remains to be seen whether earlier and more aggressive treatment of patients with not yet 'fully established' rheumatoid arthritis may succeed in preventing at least some of them from progressing to destructive arthritis.
19447771 Methotrexate, rheumatoid arthritis and infection risk: what is the evidence? 2009 Aug Low-dose MTX administered weekly remains a mainstay in the therapy of RA. There is a belief amongst rheumatologists that RA patients taking MTX have both an increased risk and severity of infection. Here we review the published data on the risks of infection associated with the use of MTX in patients with RA and make some recommendations for managing MTX in patients with infection.
21044431 Methotrexate pharmacogenetics in rheumatoid arthritis. 2010 Sep Rheumatoid arthritis (RA) is a systemic inflammatory arthritis that can not only result in permanent joint damage, but is associated with high morbidity and mortality. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs improve the symptoms of joint pain and swelling, but more importantly, prevent the progression of joint damage. Methotrexate (MTX) is the first-line DMARD in RA with over two decades worth of excellent long-term efficacy and safety. However, there is significant variability in patients' response to MTX, both in efficacy and toxicity. Recent advances in genetics, particularly pharmacogenetics, may permit the prediction, a priori, of an individual patient's response to MTX. In this review, we highlight recent published literature on the pharmacogenetics of MTX in RA. Pharmacogenetics may be a useful means of optimising MTX therapy in patients with RA.
19892679 Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologi 2009 Nov Interstitial lung disease (ILD) is a frequent extraarticular manifestation of rheumatoid arthritis (RA). While the nonspecific interstitial pneumonia pattern predominates in most forms of connective tissue-associated ILD, studies in patients with RA-associated ILD (RA-ILD) suggest that the usual interstitial pneumonia (UIP) pattern is more common in this patient population. High-resolution CT (HRCT) scans appear accurate in identifying UIP pattern in many patients with RA-ILD. Although the data are limited, UIP pattern appears to predict worse survival in RA-ILD patients. Larger, prospective, multicenter studies are needed to confirm this finding. We propose that the evaluation of patients with RA-ILD should focus on identifying those with UIP pattern on HRCT scans, as these patients are likely to carry a worse prognosis. In patients in whom the underlying pattern cannot be determined by HRCT scanning, surgical lung biopsy should be considered.
20516031 Remission in early rheumatoid arthritis. 2010 Jul OBJECTIVE: We systematically reviewed remission as an outcome measure in observational studies and randomized controlled trials (RCT) in early rheumatoid arthritis (RA). Our objectives were to identify its frequency using different criteria, to determine the influence of different treatment strategies on remission, and to review the effects of remission on radiological outcomes. METHODS: Pubmed, Medline and Embase were searched using the following terms: Early Rheumatoid Arthritis or Early RA combined with Remission, Treatment, anti-Tumor Necrosis Factor (TNF) or Disease-modifying Antirheumatic Drugs (DMARD). Remissions were reported using American College of Rheumatology (ACR) criteria and Disease Activity Score (DAS) criteria. RESULTS: Seventeen observational studies (4762 patients) reported remission in 27% of patients, 17% by ACR criteria and 33% by DAS criteria. Twenty RCT (4 comparing DMARD monotherapies, 13 comparing monotherapy with combination therapies, 3 comparing combination therapies) enrolled 4290 patients. ACR remissions occurred in 16% receiving DMARD monotherapy and 24% combination therapies (random effects OR 1.69, 95% CI 1.12-2.36). DAS remissions occurred in 26% and 42%, respectively (OR 2.01, 95% CI 1.46-2.78). Observational studies showed continuing radiological progression despite remission. RCT showed less radiological progression in remission when treated with combination therapy compared to monotherapies. CONCLUSION: Remission is a realistic treatment goal in early RA. Combination therapies using DMARD with or without TNF inhibitors increase remissions. Radiological progression occurred in remission but is reduced by combination therapies. ACR and DAS remission criteria are not directly comparable and standardization is needed.
19509324 Assessment and management of rheumatoid arthritis. 2009 Jun The goal of treatment for patients with rheumatoid arthritis (RA) is to achieve remission, or at least a low disease activity state. A variety of useful and practical tools are available to rheumatologists to assess patient prognosis and evaluate response to treatment in clinical practice. Frequent assessments, ideally every 1 to 3 months, allow rheumatologists to adjust therapy according to patient outcomes. For patients who fail to respond to treatment with classic disease modifying antirheumatic drugs, combination therapies with biologic agents offer improved outcomes.
19509328 Patient-driven outcomes in rheumatoid arthritis. 2009 Jun Clinical trials evaluating therapies for the management of rheumatoid arthritis (RA) typically report disease activity using measures such as the American College of Rheumatology response criteria and Disease Activity Scores. Additional outcomes, such as feeling well and feeling less fatigue, appear to be more important to patients than traditional disease activity outcomes such as joint tenderness and stiffness. As a result, patient-driven outcomes are increasingly used in clinical trials of RA, and have been shown to provide useful information. It is proposed that factors such as Health Assessment Questionnaire scores, fatigue, sleep, and physical and mental function become part of a patient's core set of outcomes when assessing patients with RA.