Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
19790058 No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthrit 2009 Oct OBJECTIVE: To investigate the relative importance of shared etiologies for rheumatoid arthritis (RA) and ischemic heart disease (IHD) in terms of the well-known increased risk of IHD in patients with RA, by assessing the occurrence of IHD up until the time of the onset of the first symptoms of RA. METHODS: We assessed the prevalence of a history of IHD, myocardial infarction (MI), and angina pectoris before the onset of RA symptoms in 2 large population-based case-control studies. Patients with newly diagnosed RA according to the criteria of the American College of Rheumatology were included as cases. We used data from the Swedish Early Arthritis Register study and the Swedish Epidemiologic Investigation of Rheumatoid Arthritis case-control study and from general population controls. Information on IHD, MI, and angina pectoris was obtained from the nationwide Hospital Discharge Register and from self reports. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) to compare the prevalence of a history of IHD/MI/angina pectoris among patients with RA with that among population controls. RESULTS: We could not detect any increased occurrence of IHD, MI, or angina pectoris before the onset of symptoms of RA, regardless of whether data on IHD were obtained from the Hospital Discharge Register or were self reported. As detected in the Hospital Discharge Register, the OR for IHD overall was 1.0 (95% CI 0.9-1.1), the OR for MI was 1.0 (95% CI 0.9-1.1), and the OR for angina pectoris was 1.0 (95% CI 0.9-1.2). CONCLUSION: Shared risk factors or susceptibilities for RA and IHD are likely to contribute less than RA-related factors to the increased occurrence of IHD in patients with manifest RA. Nonetheless, the existence of shared factors associated with longer latency until the occurrence of IHD cannot be excluded.
20657010 Performance on rheumatoid arthritis quality indicators in an Alaska Native healthcare syst 2010 Oct OBJECTIVE: Rheumatoid arthritis (RA) is highly prevalent in some Alaska Native and American Indian populations. Quality indicators for RA have been proposed, but these have not been widely implemented or used to assess RA care in Alaska Native or American Indian populations. METHODS: Medical records were included if they met the following criteria: RA diagnosed before October 2000 fulfilling American College of Rheumatology classification criteria; all care for RA at the Alaska Native Medical Center. Records were reviewed for a 5-year period to determine compliance with eight quality indicators defined by the Arthritis Foundation Quality Indicator Program. Multivariate logistic regression was performed to analyse associations with quality of care. RESULTS: There were 106 individuals included in the study. The highest-scoring measures were folic acid prescription if on methotrexate (93.3%) and disease-modifying antirheumatic drug prescription (90.6%). The lowest scoring measure was radiographs of both hands and feet (16.0%). In multivariate analysis, the factor most strongly associated with disease-modifying antirheumatic drug prescriptions, annual exam for RA and hand radiographs was at least one visit with a rheumatologist. CONCLUSIONS: Quality of care for RA varies by measure and is better for patients who see a rheumatologist. These data provide an initial evaluation of RA quality of care in a unique minority population with an integrated healthcare system.
20578409 Atherogenesis in rheumatoid arthritis: the "rheumatoid vasculopathy"? 2009 BACKGROUND AND AIM: Rheumatoid Arthritis (RA) is associated with accelerated atherogenesis. RA patients have a reduced life expectancy compared to the general population, and cardiovascular (CV) disease (CVD) is recognized as a strong contributor to the excess of morbidity and mortality. Our aim was to review and discuss the recent advances in the knowledge of the RA-associated atherogenesis. METHODS: A detailed search of the available literature was performed in the PubMed (U.S. National Library of Medicine) database. RESULTS: Atherosclerosis is an early and common finding in RA patients, positively correlating to the disease duration and severity. Both traditional CV risk factors and disease-related mechanisms may contribute to the RA atherogenesis, however, clinical and epidemiological studies suggest that the systemic inflammation is the major determinant of the RA vascular comorbidity. Patients with RA show an increased risk for CV events compared with the general population, and CVD accounts for nearly 50% of death causes. CV morbidity and mortality strongly correlate with disease activity, whereas the successful pharmacological control of the chronic inflammation decreases the risk of CV complications. CONCLUSIONS: Atherogenesis is a precocious feature in RA, as extraarticular manifestation of the syndrome, and might be defined the "rheumatoid vasculopathy". The better understanding of molecular mechanisms leading to the RA accelerated atherogenesis, the development of effective screening methods, and the identification of successful strategies to control both systemic inflammation and concomitant CV risk factors will allow to minimize the rheumatoid vasculopathy impact on the patients' morbidity and mortality.
20597265 [Magnetic resonance imaging of the hand as an early diagnostic method for rheumatoid arthr 2010 AIM: To provide the qualitative and quantitative characteristics of changes revealed by the data of magnetic resonance imaging (MRI) of the hand and by those of X-ray study of the hand and foot in patients with early rheumatoid arthritis (ERA). SUBJECTS AND METHODS: The study enrolled 110 patients (90 females, 20 males; age 49.6 +/- 12.2 years) examined in the framework of the RADICAL program at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. The mean duration of the disease was 5.61 +/- 3.17 months. The diagnosis of rheumatoid arthritis was established by the 1987 ARA criteria in all the patients on primary standard examination comprising X-ray study of the hand and feet and evaluation by the modified Sharp method. MRI of the hand was performed in all the patients, by assessing the result by the OMERACT-RAMRIS procedure. RESULTS: Destructive changes (cysts and erosions) evidenced by X-ray study were found in the wrists, metacarpophalangeal articulations (MPA), and foot in 7.27, 8.2, and 13.64%, respectively. MRI revealed destructions in the wrist, MPA, and metacarpal bone base in 50, 60, and 16.36%, respectively. Overall, erosions could be seen on X-ray films and MRI scans in 20.91 and 67.27%, respectively (p < 0.0001). MRI revealed bone edema (osteitis) in 46.4% of the patients; there was no difference in the detection rate between the extremities. MRI synovitis was found in 99% of the patients, the right hand being significantly more commonly affected. Detailed characterization of the changes revealed by MRI and Xray was obtained in patients with ERA. CONCLUSION: MRI detected erosions significantly more frequently than did X-ray (p < 0.001), which confirms the high value of low-field MRI diagnosis on primary examination of patients with ERA and supports the opinion that the results of this study should be included into the diagnostic criteria of ERA.
20044040 Switching TNF-alpha antagonists in rheumatoid arthritis: the experience of the LORHEN regi 2010 Apr New biologic agents have changed the paradigm of rheumatoid arthritis treatment, leading to improvement in managing patients' refractory to classical DMARDs. Anti-TNF-alpha is used as first-line treatment in patients failing to respond to classical DMARDs. However, up to 50% of patients fail to respond to these drugs or develop adverse events leading to treatment discontinuation: in these cases the optimal treatment strategy is still a matter of debate even if trying with a second anti-TNF-alpha is considered a good option. We report data of patients switching from a first to a second anti-TNF-alpha from an Italian registry of patients with rheumatoid arthritis, showing that switching is valuable in patients stopping a first anti-TNFalpha drug. The patients with higher disease activity levels and those stopping the first anti-TNFalpha treatment because of a lack of efficacy are very likely to respond to the second treatment.
19522556 Atacicept, a novel B cell-targeting biological therapy for the treatment of rheumatoid art 2009 Jul BACKGROUND: Recent data suggest a key role for B cells in the pathogenesis of many autoimmune diseases including rheumatoid arthritis (RA), and biological therapies targeting B cells are promising treatments for patients with RA. Atacicept inhibits B cell maturation, differentiation and survival, and immunoglobulin production by depriving B cells of growth and development signals. Therefore, atacicept may represent an effective strategy in RA treatment. OBJECTIVE: To evaluate the potential value of atacicept in RA treatment based on preclinical and clinical studies. METHODS: Preclinical and clinical data on atacicept were identified using PubMed and systematically reviewed. RESULTS/CONCLUSION: Preclinical and clinical studies show that atacicept is well tolerated, with no increased incidence of infections. Atacicept displays non-linear pharmacokinetics, with a more than dose-proportional increase in free drug and less than dose-proportional, saturated increase in atacicept-ligand complex. Overall, the pharmacokinetic profiles of atacicept were consistent, dose-related and predictable. Dose-dependent reductions in immunoglobulins and other biomarkers, including rheumatoid factor, occurred rapidly but returned to baseline after discontinuation. There was a biphasic response in B cell number, but no effect on other leucocytes. Atacicept improved the signs and symptoms of RA, although larger studies are needed to confirm its efficacy and its optimal use.
20049501 Diagnostic value of anti-cyclic citrullinated peptide antibodies in northern Chinese Han p 2010 Apr This study was to evaluate the diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies in northern Chinese Han patients with rheumatoid arthritis (RA) and its correlation with disease activity. Clinical data and serum samples were collected from 112 RA patients and 55 non-RA patients. Statistical analyses of the correlations among anti-CCP antibodies, other serological markers, and the RA patients' clinical characteristics were performed using SPSS 11.5 software. Anti-CCP antibodies were detected in 77.7% of all RA patients and 80.4% of the RA patients with a disease duration of 3 years or less. The combined diagnosis using high titer anti-CCP antibodies (>or=100 RU/ml) with a concomitant positive rheumatoid factor (RF) test exhibited the greatest diagnostic specificity; it achieved 87.9% for all RA patients and 90.1% for the patients with disease duration of three years or less. Moreover, anti-CCP antibodies showed medium correlations to the RA patient's serum RF titer (r = 0.560, P < 0.001) and disease activity (DAS28 score; r = 0.404, P < 0.001). Compared with the patients with low anti-CCP antibody titers (<100 RU/ml), patients with high anti-CCP antibody titers showed higher RF titers, worse DAS28 scores, and severe morning stiffness (P < 0.01). This study suggests that anti-CCP antibodies can be used for RA diagnosis and disease activity evaluation for northern Han Chinese patients. A combined diagnosis using both high titers of anti-CCP antibodies (>or=100 RU/ml) and a positive RF test markedly improves RA diagnostic specificity. Patients' DAS28 scores rise and morning stiffness intensifies with increasing anti-CCP antibody titers.
19687077 Radiolunate fusion in the rheumatoid wrist with Shapiro staples: clinical and radiological 2010 May We performed a retrospective clinical and radiological case control study on 22 rheumatoid wrists following radiolunate fusion via Shapiro staples with a mean follow-up of 5 years. Radiographs showed one early loosening through dorsal staple migration and four nonunions. Six wrists fused in mild ulnopalmar dislocation of the lunate. Primary intra-articular positioning of a staple was found in nine wrists, secondary intra-articular staple dislocation was found in two wrists. Dorsal staple dislocation was found in four fused arthrodeses. Osteolysis around the staples was found in all but two wrists. In contrast to unsatisfactory radiological results the clinical results were good or excellent in 18 patients. Good and excellent clinical results in the majority of the patients following radiolunate fusion does not depend on the fixation device. Nevertheless staple fixation of the radiolunate joint in the rheumatoid wrist is associated with a high rate of radiological complications.
19095696 Calprotectin (a major S100 leucocyte protein) predicts 10-year radiographic progression in 2010 Jan BACKGROUND: Plasma levels of calprotectin, a major S100 leucocyte protein, are cross-sectionally associated with clinical and laboratory markers of inflammation and with radiographic damage in rheumatoid arthritis (RA). High amounts of calprotectin are found in synovial fluid from patients with RA. OBJECTIVE: To examine whether calprotectin might be an independent predictor of joint destruction over time. METHODS: 124 patients with RA were assessed at baseline and after 10 years with inflammatory markers (calprotectin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)), serological variables (antibodies to cyclic citrullinated peptide (anti-CCP), IgA rheumatoid factor (RF) and IgM RF) and radiographic and clinical assessments of joint damage (hand radiographs and Rheumatoid Arthritis Articular Damage (RAAD) score). Progression of radiographic damage was assessed according to the van der Heijde modified Sharp score. RESULTS: At both examinations the highest calprotectin levels were found in patients positive for anti-CCP, IgA and IgM RF. Calprotectin had moderate to good correlations with inflammatory and serological markers (r = 0.41-0.67). Patients with normal baseline calprotectin levels had a lower degree of joint damage. High univariate associations were found between baseline calprotectin levels and progression in the Sharp score as well as the RAAD score. Baseline calprotectin was independently associated with progression in the Sharp score and with the RAAD score in multiple linear regression analyses, including baseline levels of CRP, ESR, anti-CCP in addition to demographic variables. CONCLUSION: Calprotectin was an independent predictor of clinical and radiographic joint damage after 10 years. These findings support the proposal that calprotectin may be a prognostic biomarker for erosive disease in patients with RA.
20682616 Are lipid ratios less susceptible to change with systemic inflammation than individual lip 2011 Feb Rheumatoid arthritis (RA) associates with excess cardiovascular risk and there is a need to assess that risk. However, individual lipid levels may be influenced by disease activity and drug use, whereas lipid ratios may be more robust. A cross-sectional cohort of 400 consecutive patients was used to establish factors that influenced individual lipid levels and lipid ratios in RA, using multiple regression models. A further longitudinal cohort of 550 patients with RA was used to confirm these findings, using generalized estimating equations. Cross-sectionally, higher C-reactive protein (CRP) levels correlated with lower levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol ([HDL-C] P ≤ .015), whereas lipid ratios did not correlate with CRP. The findings were broadly replicated in the longitudinal data. In summary, the effects of inflammation on individual lipid levels may underestimate lipid-associated cardiovascular disease (CVD) risk in RA, thus lipid ratios may be more appropriate for CVD risk stratification in RA.
20627791 Chronic eosinophilic pneumonia (Carrington's disease) and rheumatoid arthritis. 2010 Oct We describe the case of a 60-year-old woman with chronic eosinophilic pneumonia (Carrington's disease) who developed symmetric rheumatoid factor-negative polyarthritis suggestive of rheumatoid arthritis. Although these two diseases are well documented as separate entities, 10 cases in the literature suggest possible links. However, the course in our patient raised the possibility of Churg-Strauss syndrome, a condition that may overlap with chronic eosinophilic pneumonia.
19419297 Bilateral fractures of the femur diaphysis in a patient with rheumatoid arthritis on long- 2009 Oct Unusual fractures of the femur diaphysis have been reported in patients treated with alendronate and, although no causal relationship has been established, excessive suppression of bone turnover and length of treatment with alendronate have been implicated in their pathogenesis. We report here clinical, biochemical, and radiological findings of a patient with rheumatoid arthritis and multiple risk factors for fractures who was treated with alendronate for 8 yr and developed spontaneous bilateral subtrochanteric/diaphyseal fractures. Bone biopsies obtained form the iliac crest and the femur showed decreased bone formation with histomorphometric evidence of markedly increased bone resorption at the femur. These results show for the first time that an imbalance between bone resorption and bone formation at the affected bone is associated with the occurrence of these atypical femur fractures. The cause of this imbalance is currently unknown, and further studies of the epidemiology and pathogenesis of diaphyseal femur fractures are warranted.
20429264 The effects of combined therapy of rheumatoid arthritis on the acute phase reactants. 2009 The paper presents the results of studies of acute phase reactants in the 60 treated patients with rheumatoid arthritis. Patients were divided into two groups, depending on the applied treatment: group I (n = 30) was treated with methotrexate, sulfasalazine and hydroxychloroquine, and group II (n = 30) with methotrexate. The results of our study shows that there is a statistically significant reduction in the value of acute phase reactants and clinical parameters after treatment in both investigated groups of patients, and also a significant statistical difference between the first and second group of treated patients.
21044426 Clinical trials to establish methotrexate as a therapy for rheumatoid arthritis. 2010 Sep The development of methotrexate (MTX) as a therapy for rheumatoid arthritis (RA) evolved initially from positive case reports, uncontrolled case series and then several decades later placebo controlled studies followed by active comparator studies. These studies established MTX as a major therapy for RA. The importance of MTX in the treatment paradigm has only been enhanced over the past decade by the increased efficacy observed when small molecules and biologics are added to MTX. Since the first randomised studies were performed in the 1980s, MTX has now become the most well-studied disease modifying therapy to date and the most popular drug worldwide in the treatment of RA. This chapter will review the history of the development of MTX in RA.
20051161 [Practice guideline 'Diagnosis and treatment of rheumatoid arthritis']. 2009 Treatment early in the course of the disease, along with early diagnosis, has a positive influence on clinical outcome in patients with rheumatoid arthritis (RA). Therapeutic strategies, including the use of 'disease-modifying antirheumatic drug' (DMARD) combinations, have proved effective, with relatively few side effects. New insights into the pathophysiology of RA have lead to the development of novel therapeutic agents that have been demonstrated to be highly effective. Patients should be monitored intensively with respect to the effect of therapy on reduction of disease activity, followed by modification of therapeutic strategy in the case of a suboptimal treatment response. Various non-pharmacological interventions, such as exercise therapy and patient education, are available to help patients to cope with the consequences of the disease. Optimizing treatment of RA by means of this approach will help to realize the goal of current therapy: to achieve and sustain remission and, thereby, an optimal functional level.
20223711 The role of microRNA in rheumatoid arthritis and other autoimmune diseases. 2010 Jul MicroRNAs (miRNAs) represent a class of non-coding RNA molecules playing pivotal roles in cellular and developmental processes. miRNAs modulate the expression of multiple target genes at the post-transcriptional level and are predicted to affect up to one-third of all human protein-encoding genes. Recently, miRNA involvement in the adaptive and innate immune systems has been recognized. Rheumatoid arthritis serves an example of a chronic inflammatory disorder in which miRNAs modulate the inflammatory process in the joints, with the potential to serve as biomarkers for both the inflammatory process and the potential for therapeutic response. This review discusses the investigations that led to miRNA discovery, miRNA biogenesis and mode of action, and the diverse roles of miRNAs in modulating the immune and inflammatory responses. We conclude with a discussion of the implications of miRNA biology in rheumatoid arthritis and other autoimmune disorders.
20465156 Histamine index and clinical expression of rheumatoid arthritis activity. 2010 Apr BACKGROUND/AIM: Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. METHODS: Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. RESULTS: Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significiant difference in the histamine index which was increased proportionally with disease activity. CONCLUSION: Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.
20697896 Mechanisms of strength gain in a handgrip exercise programme in rheumatoid arthritis. 2012 Jan In a progressive resistive strengthening programme, healthy individuals gain strength initially through neural adaptation followed by increases in muscle mass. Programmes are designed to maximise these responses. The physiological mechanisms of strength gain in RA are unknown, but their identification will help to develop more effective exercise programmes. The aim of this study was to investigate the responses to a 12-week isometric handgrip strengthening programme in female subjects with RA. Fourteen right-handed female subjects with RA and 14 age-matched female controls participated in a 12-week right handgrip strengthening programme. Maximum grip strength (MGS) and disease activity were measured serially over 12 weeks. Forearm muscle volume was measured using MRI at baseline and 12 weeks. Significant gains in right handgrip strength were noted in both groups, the gains being most marked in those with RA: mean (SD; range) MGS (mmHg) in RA group at baseline 105.1 (48.1; 34-108) and 174.8 (76.4; 50-340) at 12 weeks. Mean (SD; range) MGS in control group at baseline 311.7 (49.6; 220-370) and 357.0 (67.1; 250-540) at 12 weeks. Significant increases in forearm muscle volume occurred in the controls, correlating with gains in strength. No such changes were noted in the RA group, indicating that improvements were solely related to neural adaptation. Response to strength training in RA differs from those of healthy individuals. Significant gains in strength in individuals with RA can occur due to neural adaptation without gains in muscle mass during a strengthening programme. This has implications for the design of rehabilitation programmes for such subjects.
19275724 The role of WNT in rheumatoid arthritis and its therapeutic implication. 2009 Mar Rheumatoid arthritis (RA) is a systematic inflammatory and intractable disease, which progressively affects multiple joints. Recent findings strongly suggest a key role of WNT signaling in the disease initiation and progression. In this review, we discuss the role and possibility of treatment by targeting WNT signaling.
19578861 [Antibodies against citrullinated peptides in clinical practice and research]. 2009 Aug Since their original description ten years ago, antibodies against citrullinated peptide antigens (ACPA) have become increasingly important in the diagnosis of rheumatoid arthritis (RA). They are now considered superior to the rheumatoid factor because they can be detected earlier in the course of the disease and are more specific while showing a comparable sensitivity. However, they seem to be less suitable for monitoring specific responses to therapies and for predicting extra-articular manifestations as well as disease activity. Recent research activities center around using ACPA to further elucidate the pathogenesis of RA.