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ID PMID Title PublicationDate abstract
24609760 Hypereosinophilia and seroconversion of rheumatoid arthritis. 2014 Nov At the intersection of atopy and autoimmunity, we present a patient with seronegative rheumatoid arthritis (RA) who developed hypereosinophilia, without evidence of other etiologies, as she became rheumatoid factor (RF) positive. Although the magnitude of eosinophilia in patients with RA has been thought to reflect the severity or activity of the RA, in our patient, eosinophilia developed at a time when the patient's synovitis was well controlled. Although eosinophilia may reflect associated drug hypersensitivity, discontinuation of the medications utilized to control our patient's disease, adalimumab and methotrexate, did not promote clinical improvement. Probably the most curious aspect of our patient was the concomitant development of rheumatoid factor seropositivity in the setting of previously seronegative RA. The temporal relationship between the development of peripheral eosinophilia and seroconversion suggests a possible connection between these events. We speculate that the T cell cytokine production that can induce eosinophilia may simultaneously activate RF production.
24783461 Increased cardiovascular risk in patients with rheumatoid arthritis: an overview. 2014 Apr Patients with established rheumatoid arthritis (RA) have a higher cardiovascular morbidity and mortality in comparison with the general population. It is considered to be an independent risk factor for cardiovascular disease. The purpose of this article is to describe the mechanisms responsible for accelerated atherogenesis in RA patients and to give an overview of the effects of different RA therapies (methotrexate, TNF antagonists and other biologicals).
24219036 Update on methotrexate as the anchor drug for rheumatoid arthritis. 2013 Methotrexate has become the "anchor drug" for rheumatoid arthritis (RA), taken by many more patients than any other disease modifying anti-rheumatic drug (DMARD) or biological agent. Methotrexate has greater efficacy and effectiveness than any other non-biologic DMARD, and greater tolerability and safety than other DMARDs. The efficacy of methotrexate is comparable to biologic agents in parallel clinical trials of DMARD-naïve patients. Adequate responses to methotrexate monotherapy or combinations with other non-biologic DMARDs are seen in about two- thirds of patients with RA in usual care. The most efficacious treatments for RA reported in the rheumatology literature are seen in strategy trials with methotrexate as the anchor drug, without any biologic agent. Interpretation of significantly lower radiographic progression between methotrexate and biologic agents in clinical trials is over- stated regarding clinic consequences. The admonition to patients to refrain entirely from consumption of alcohol while taking methotrexate may be unnecessary. Accurate information concerning methotrexate as the anchor drug for RA should lead to better understanding of optimal use and better to patient outcomes in usual clinical care.
24151946 Monotherapy in rheumatoid arthritis. 2013 Therapeutic strategies for rheumatoid arthritis (RA) have evolved over time. Novel therapies have morphed in parallel to the ever-increasing understanding of RA pathogenesis, diagnosis and outcomes tools. For a century, the principal armamentarium was mainly composed by steroidal and non-steroidal anti-inflammatories. Over the last 25 years, however, the concept of disease-modifying anti-rheumatic drugs (DMARDs) has made possible the notion that the natural history of RA could actually be altered. Since then, synthetic DMARDs-particularly methotrexate (MTX) -have been used as monotherapy with significant success. This was followed by a revolutionary paradigm shift with the advent of anti-TNFα inhibitors and other "biologics" in the 1990s. Contemporary guidelines advocate for the use of a combina- tion therapy (i.e., MTX and a biologic) in aggressive RA cases given their proven additive effect. However, some patients are either intolerant to synthetic DMARDs or develop side effects that preclude their use. New data has recently emerged point- ing towards the potential for biologic monotherapy regimens in certain RA cases. This review will, therefore, describe the available evidence supporting the use of biologic DMARDs and the circumstances in which they are indicated.
24219038 The role of concomitant methotrexate in biologic therapy for rheumatoid arthritis. 2013 From the first use of biologic therapy for the management of rheumatoid arthritis, methotrexate (MTX) has been commonly used as co-therapy. There are a number of mechanistic reasons why MTX may improve the efficacy of biologics, including reduced antigenicity as well as reduced clearance of the biologic agent. Clinical trial data for tumor necrosis factor inhibitors and for other biologic agents does suggest added efficacy when these agents are used in combination with MTX. One exception may be the interleukin-6 receptor antibody tocilizumab, for which there is some data to suggest that monotherapy may be as effective as combined therapy with MTX. Post-marketing registry data also supports the concomitant use of MTX with biologics, with evidence for greater efficacy and longer persistence on treatment when compared with monotherapy.
24394994 CCR6 and CCL20: emerging players in the pathogenesis of rheumatoid arthritis. 2014 Apr The therapeutic targeting of pro-inflammatory TNF with neutralising biological anti-TNF agents, often in combination with other disease-modifying anti-rheumatic drugs, such as the purine synthesis inhibitor methotrexate has been the first major break-through in the treatment of chronic inflammatory diseases in decades. There are however, side effects and disadvantages of these treatments, such as general immunosuppression as well as therapy resistance in a large proportion of patients. This evokes the wish for other, more specialised forms of treatments. The targeting of chemokines and their receptors to disrupt cell movement specifically has been seen as a promising avenue of therapy for a considerable time. We will discuss one particular chemokine and its receptor, the C-C chemokine ligand CCL20 and the C-C chemokine receptor CCR6, and summarise its genetic and biological role in rheumatoid arthritis (RA). CCR6 has been associated with RA in genome-wide association studies and has been shown to be an interesting candidate for a therapeutic approach, considering its and CCL20's expression patterns within the tissue as well as the immune system.
24205507 The multifaceted aspects of interstitial lung disease in rheumatoid arthritis. 2013 Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD) significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP) is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP); other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.
25365086 Vectra DA for the objective measurement of disease activity in patients with rheumatoid ar 2014 Sep Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.
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.
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.
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.
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.
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.
23592710 Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: a syst 2014 Jan BACKGROUND: The 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) were developed to improve the identification of individuals for studies of RA. We aimed to summarise the performance of the criteria based on the published literature. METHODS: We performed a systematic literature search to identify all studies investigating the 2010 criteria and reporting data allowing to calculate sensitivity (SENS), specificity (SPEC), and positive and negative predictive values. Where possible, meta-analysis was performed. RESULTS: Seventeen full articles (total 6816 patients) and 17 meeting abstracts (total 4004 patients) fulfilled the inclusion criteria. Pooled sensitivity and specificity for RA (defined by different reference standards) were 0.82 (95% CI 0.79-0.84) and 0.61 (0.59-0.64). Results were comparable for different reference standards: for initiation of methotrexate pooled sensitivity was 0.85 (0.83-0.86) and specificity was 0.52 (0.49-0.54); for initiation of any disease modifying antirheumatic drug they were 0.80 (0.79-0.82) and 0.65 (0.61-0.68), respectively; and for expert opinion 0.88 (0.86-0.90) and 0.48 (0.35-0.52). No differences were observed for use of different types of joint counts. Eight studies and five meeting abstracts directly compared 1987 and 2010 criteria using different reference standards within different target populations showing higher overall sensitivity (+0.11 compared with 1987 criteria) at the cost of lower overall specificity (-0.04). CONCLUSIONS: Two years after their publication, the 2010 ACR/EULAR criteria have been widely tested in the community. They are sensitive to detect cases of RA among various target populations, independent of how the latter is referenced.
24219039 Evidence that the strategy is more important than the agent to treat rheumatoid arthritis. 2013 Eight major "strategy trials" in rheumatoid arthritis (RA) are reviewed, with protocol-driven escalation of combinations of methotrexate and other small molecule non-biological disease modifying antirheumatic drugs (DMARDs). All documented the value of intensive treatment adjusted according to quantitative data, generally a disease activity score (DAS) or its 28 joint count version (DAS28). Three of the 8 trials, TICORA, Dutch DAS-driven care, and CAMERA, may be termed "pure strategy trials," to com- pare a protocol-driven "intensive" strategy to usual care. Five other trials, BeSt, CIMESTRA, TICORA 2, Step-down versus step-up, and TEAR, may be termed "hybrid trials," in which an initial parallel design was supplemented with incremental protocol-driven intensification of treatment. A strategy of aiming for low disease activity or remission appears more important than the specific agent used. In group data, the proportion of good responses seen in these trials with combinations of non-biologic, small molecule DMARDs are comparable to data from clinical trials of biological agents although responses appear more rapid with biological agents, and certain individual patients may require a biologic agent for adequate control. These trials also illustrate the value of a quantitative index, monitored frequently for rational intensification of therapy. The data make a compelling case for both routine monitoring with a quantitative index and consideration of routine adjustment of therapy at each visit. Combinations of methotrexate with other non-biologic DMARDs and glucocorticoids, toward a target of low disease activity or remission, may improve outcomes for patients with RA at levels similar to biologic agents in many patients.
23961662 [Pharmacological management of rheumatoid arthritis: the state of the art and the future p 2013 Jul Pharmacological management of rheumatoid arthritis (RA) has been rapidly progressed in recent years, which is appeared in the "treat to target" movement and the recommendations developed by some established international/domestic rheumatology associations. The baseline evaluation of poor prognostic factors as well as disease activity with composite measures is necessary for a personalized management. Methotrexate is currently the anchor drug, and other conventional or biological antirheumatic drugs should be added to it for refractory patients. The development of various novel agents including signal transduction inhibitors should promote further advances in the management of RA and other systemic autoimmune and/or inflammatory diseases.
23649300 [Why rheumatoid arthritis needs cardiologists]. 2013 May Rheumatoid arthritis (RA) is associated with a shortened life expectancy. Most premature deaths are caused by cardiovascular (CV) events; therefore it is of importance to consider the increased CV risk when treating RA patients. Traditional CV risk factors cannot fully explain the increased risk but the common understanding is that inflammation significantly contributes to the excess risk observed. Without the use of correction factors commonly used risk calculators underestimate the true CV risk in RA patients. Methotrexate and TNF inhibitors appear to be beneficial with regard to the CV risk. To date there are only few recommendations for interventions in the CV system of RA patients which go beyond those formulated for the general population. The present manuscript summarizes the published evidence concerning the increased CV risk in RA patients.
22798565 Rheumatoid factor determines structural progression of rheumatoid arthritis dependent and 2013 Jun BACKGROUND: Rheumatoid factor (RF) is prototypic for rheumatoid arthritis (RA) and serves diagnostic and prognostic purposes. RF is associated with joint destruction, but the role of disease activity as a potential mediator of these effects has not been clearly elucidated yet. OBJECTIVE: To investigate if higher radiographic progression (Sharp score, ΔTSS) in RF+ patients is dependent or independent of disease activity. METHODS: The authors performed a cross-sectional multivariate analysis at baseline and a matched cohort study in patients from five RA clinical trials. The authors pooled methotrexate treatment arms and compared ΔTSS in RF+ and RF- patients before and after matching for other associated variables. RESULTS: Among 686 patients, 124 were RF- and 562 RF+, 343 having high (>160 U/ml) RF. ΔTSS was 1.03±5.83, 3.23±8.10 and 3.58±8.18 (p<0.0001), respectively, and similarly for erosions and joint space narrowing (JSN). After matching for other prognostically important variables, ΔTSS still was lower among 61 RF- versus 61 RF high+ patients (0.52±2.47 vs 3.09±8.28; p=0.028), mainly related to differences in erosion score (0.31±1.88 vs 2.07±5.62; p=0.035), but not JSN (0.21±1.26 vs 1.02±3.31; p=0.162). CONCLUSIONS: The data reveal that damage progression in seropositive RA patients is related to higher levels of disease activity and to independent effects of RF, particularly on bone damage. This calls for consideration of RF status irrespective of disease activity.
23961658 [Paradigm shift and future perspectives in rheumatoid arthritis]. 2013 Jul Introduction of methotrexate (MTX) and biologic agents caused a paradigm shift in the treatment of rheumatoid arthritis(RA). Development of new classification criteria for RA was established in 2010, which makes early diagnosis of RA possible. Treating to target (T2T) by setting treatment goal avoids irreversible joint damage and disability in RA. Remission, thus became a realistic goal with early diagnosis and intervention. Consequently, not only clinical but also structural and functional remission can be achieved with the current treatment. However, risk managements with the use of these agents are also of importance. In addition, there remains unmet needs in RA treatment.
26010598 Clinical profile of 266 Filipino patients with rheumatoid arthritis included in the rheuma 2015 May AIM: To describe Filipino patients with rheumatoid arthritis (RA) entered in the Rheumatoid arthritis database and registry (RADAR) of the Philippine General Hospital. METHODS: Cases entered to RADAR from 2010-2012 were included. All fulfilled the 1987 American College of Rheumatology criteria for classification of RA. Included cases gave written infomed consent. Data extracted were demographics, clinical presentation, laboratory tests, treatment and disease course. Means and proportions were used for population characteristics. RESULTS: Two hundred and sixty-six cases were included. Mean age was 44 years, with 9 : 1 female preponderance and mean diagnosis time of 5 years. There was symmetrical polyarthritis with high tender and swollen joint count and mean Disease Activity Score of 28 joints, erythrocyte sedimentation rate of 5.27 (3.39, 8.13). Rheumatoid factor was positive in 2/3 of cases. Hypertension, tuberculosis and diabetes were important co-morbidities. Treatment included prednisone, non-steroidal anti-inflammatory drugs and methotrexate. At 12 months of treatment, evaluable cases (< 20%) showed improvement from high to moderate disease activity. Methotrexate average dose was 8.6 mg/week. Nine cases received biologic agents. Factors affecting treatment included access to rheumatology centers, low socioeconomic status, presence of co-morbid diseases and treatment adverse events. CONCLUSION: This study reports a cohort of Filipino RA patients seen in a government arthritis unit whose disease characteristics are similar to what is reported worldwide. This cohort differs from most studies in having a high female to male ratio, a long delay in diagnosis, and high attrition rate. Mean methotrexate dose was low and there was less access to biologic disease-modifying anti-rheumatic drugs.