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

ID PMID Title PublicationDate abstract
19938416 [Rheumatoid arthritis (updated Current Care guideline)]. 2009 Anti-citrulline antibodies are highly specific to rheumatoid arthritis (RA) and are thus helpful in differential diagnosis. Early and aggressive disease modifying anti-rheumatic drug (DMARD) therapy is essential for a positive treatment result in cases of RA. Remission during the 1st year of treatment predicts permanent remission, milder joint damage and better functional ability. It is recommended that patients with an unsatisfactory response to DMARDs, including methotrexate and a combination of DMARDs, should be treated primarily with TNF blockers, and non-responders with rituximab or abatacept. RA is an independent risk factor for cardiovascular diseases. The assessment of cardiovascular risk must not be forgotten in daily practice.
20196859 The loss of health status in rheumatoid arthritis and the effect of biologic therapy: a lo 2010 INTRODUCTION: The long-term course of rheumatoid arthritis (RA) in terms of health status is not well understood, nor is the degree of effectiveness of biologic therapy in the community. We modeled the progression of loss of health status, and measured incremental costs and effectiveness of biologic therapy in the community. METHODS: We studied change in function and health status in 18,485 RA patients (135,731 observations) at six-month intervals for up to 11 years, including a group of 4,911 patients (59,630 observations) who switched to biologic therapy from non-biologic therapy. We measured the SF-36 Physical Component (PCS) and Mental Component (MCS) Summary scales, the EQ-5D health utility scale, and the Health Assessment Questionnaire (HAQ) disability scale; and we calculated treatment and direct medical costs. RESULTS: RA onset caused an immediate and substantial reduction in physical but not mental health status. Thereafter, the progression of dysfunction in RA was very slow (HAQ 0.016 units and PCS -0.125 units annually), only slightly worse than the age and sex-adjusted US population. We estimated biologic treatment to improve HAQ by 0.29 units, PCS by 5.3 units, and EQ-5D by 0.05 units over a 10-year period. The estimated incremental 10-year total direct medical cost for this benefit was $159,140. CONCLUSIONS: Biologic therapy retards RA progression, but its effect is far less than is seen in clinical trials. In the community, cost-effectiveness is substantially less than that estimated from clinical trial data. The study results represent the incremental benefit of adding biologic therapy to optimum non-biologic therapy.
20032104 Linkage and association studies of joint morbidity from rheumatoid arthritis. 2010 Feb OBJECTIVE: To investigate the relationship between genetic variations of rheumatoid arthritis (RA) susceptibility in terms of joint morbidity. METHODS: We used data from Genetic Analysis Workshop 15. The Illumina linkage panel IV included 5858 single-nucleotide polymorphisms (SNP), with 5744 SNP passing quality control filters. The phenotypic variables analyzed were the level of rheumatoid factor (RF) and score on the Joint Alignment and Motion (JAM) scale. We modified the scale, dividing by RF values relevant to disease severity. Linkage analysis for affected sibling pairs was done using the MERLIN program, and family-based association tests were carried out using PLINK and FBAT software. RESULTS: We found a high peak (LOD = 3.29; NPL Z = 4.07) near the HLA-DRB1 region on chromosome 6. The linkage at 6p24 at rs1410766 [LOD = 2.66; nonparametric linkage (NPL) Z = 3.23] was statistically significant. Two other regions also showed possible linkage peaks: chromosome 7q30 at rs322812 (LOD = 2.47; NPL Z = 3.39) and chromosome 15p34 at rs347117 (LOD = 1.95; NPL Z = 2.80). For the family-based association study, 7 SNP related to clinical RA severity were detected. CONCLUSION: Genetic variations may lead to an enhanced risk of joint damage and increased levels of RF. Further studies are needed to elucidate the roles of other genes involved in RA and to explore whether the clinical signs of RA are associated with particular genetic variations.
20929970 An evaluation of the strengths and weaknesses of a register of newly diagnosed rheumatoid 2011 Jan OBJECTIVES: To evaluate the strengths and weaknesses of a register of management and outcomes of recently diagnosed RA, and allow comparisons between rheumatology centres on good clinical practice and guidelines. METHODS: A register of newly diagnosed RA was initiated in 1986 in nine different regions of England, later expanded to UK-wide membership in 2002. Standardized data collection includes disease activity, function, radiological damage, therapy, hospitalizations, major comorbidity and mortality. A centralized database generates individual reports and comparative data for each centre yearly. Aims have been compared with actual achievements and any changes over 25 years. RESULTS: Thirty rheumatology centres have recruited 2866 patients. Study outputs have included peer-reviewed scientific publications and contributions to the recent National Audit Office report on RA. Referral times into secondary care have changed little over 25 years, but time to initiation of drug therapies has decreased. Delays between publication of clinical trial evidence and management guidelines and their implementation in normal clinical practice are illustrated by relatively infrequent use of combination therapies at diagnosis. Consecutive case recruitment, centre participation and follow-up were reportedly compromised by local funding issues. Centre participants report a benefit from feedback of actual clinical practice compared with recommended standards of care. CONCLUSIONS: Most of the original objectives have been achieved. Cohort studies based predominantly in District General Hospitals provide unique insights into the natural history and impact of RA, its management, the translation of research findings into clinical practice and provide participating centres with important clinical governance and professional development opportunities.
20551110 Influence of IL6R rs8192284 polymorphism status in disease activity in rheumatoid arthriti 2010 Aug 1 OBJECTIVE: To analyze the influence of IL6R rs8192284 polymorphism on the disease activity of rheumatoid arthritis (RA). METHODS: Patients with RA (n = 281) were followed for a median of 4.2 years. A total of 1143 disease activity measurements using the 28-joint count Disease Activity Score (DAS28) were performed. A mixed-effect model was used to analyze the measurements. RESULTS: A statistically significant interaction was observed between IL6R rs8192284 polymorphism and the presence of anticyclic citrullinated peptide (anti-CCP) antibodies (p = 0.008). An inverse relationship between the polymorphism and DAS28 was observed depending on anti-CCP status. CONCLUSION: The anti-CCP status in patients with RA determines the association between the IL6R rs8192284 polymorphism and disease activity.
21149486 18F-FDG PET as a tool to predict the clinical outcome of infliximab treatment of rheumatoi 2011 Jan 18F-FDG PET is a sensitive, promising method for visualizing disease activity in rheumatoid arthritis. This study aimed to assess the association between changes in 18F-FDG joint uptake after 2 wk of infliximab treatment and clinical outcome. METHODS: Scans were obtained at the initiation of treatment and at 2 wk. Uptake in metacarpophalangeal and wrist joints was quantified using standardized uptake values. RESULTS: Changes in mean standardized uptake value at 0-2 wk significantly correlated with the disease activity score (DAS) at 14 and 22 wk and contributed significantly to the prediction of DAS at these time points. No significant correlation was found between changes in acute-phase reactants at 0-2 wk and the DAS at later time points. CONCLUSION: Early changes in 18F-FDG uptake in joints during infliximab treatment of rheumatoid arthritis patients, using PET, may predict clinical outcome.
19337783 Therapeutic effects of acupuncture in patients with rheumatoid arthritis: a prospective st 2009 May OBJECTIVE: The purpose of this study was to investigate whether improvement of regional inflammatory findings in knee joints of rheumatoid arthritis (RA) could be detected by positron-emission tomography (PET) using (18)F-Fluorodeoxyglucose (FDG) after acupuncture treatments, as well as improvement of systemic inflammatory markers. METHODS: Six RA patients (all female, 61 +/- 12 years old) received 10 acupuncture treatments in 2 months, to 11 traditional acupuncture points around a knee joint considered effective on RA. A visual analogue scale (VAS) for intensity of pain, knee joint range of motion (ROM), face scale for patient mood, and modified health assessment questionnaire (MHAQ) for disability of daily activities were assessed just before and after acupuncture. Maximum standardized uptake value (SUV(max)) and the volume with SUV more than 1.0 [Volume(SUV > 1)] on FDG-PET images as well as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also measured before and after the treatments. RESULTS: VAS, ROM, face scale and MHAQ improved in all patients and significantly after acupuncture, but no significant change was detected in ESR, CRP, SUV(max), or Volume(SUV > 1). CONCLUSIONS: Acupuncture relieves symptom, remedies physical function, and improves quality of life in RA patients, but may have no or very limited anti-inflammatory effect systemically. The regional effects of acupuncture are unlikely to be induced through reduction of regional inflammation. We believe this clinical study is the first step for elucidating therapeutic mechanisms of acupuncture, which must be important for the rational use and further development of acupuncture.
20329696 Low frequency pulsed electromagnetic field--a viable alternative therapy for arthritis. 2009 Dec Arthritis refers to more than 100 disorders of the musculoskeletal system. The existing pharmacological interventions for arthritis offer only symptomatic relief and they are not definitive and curative. Magnetic healing has been known from antiquity and it is evolved to the present times with the advent of electromagnetism. The original basis for the trial of this form of therapy is the interaction between the biological systems with the natural magnetic fields. Optimization of the physical window comprising the electromagnetic field generator and signal properties (frequency, intensity, duration, waveform) with the biological window, inclusive of the experimental model, age and stimulus has helped in achieving consistent beneficial results. Low frequency pulsed electromagnetic field (PEMF) can provide noninvasive, safe and easy to apply method to treat pain, inflammation and dysfunctions associated with rheumatoid arthritis (RA) and osteoarthritis (OA) and PEMF has a long term record of safety. This review focusses on the therapeutic application of PEMF in the treatment of these forms of arthritis. The analysis of various studies (animal models of arthritis, cell culture systems and clinical trials) reporting the use of PEMF for arthritis cure has conclusively shown that PEMF not only alleviates the pain in the arthritis condition but it also affords chondroprotection, exerts antiinflammatory action and helps in bone remodeling and this could be developed as a viable alternative for arthritis therapy.
20052478 Elevation of serum IgG subclass concentration in patients with rheumatoid arthritis. 2010 Apr A new concept of IgG subclass such as IgG4-related systemic disease including autoimmune pancreatitis, characterized by a high-serum IgG4 level, has been proposed. Our aim was to investigate serum IgG subclass levels in rheumatoid arthritis (RA). IgG subclass levels of sera from 72 patients with rheumatoid arthritis were determined by immunonephelometric assay. The patients were divided into two groups according to clinical activity of the disease: active disease and remission. The sera from 45 normal controls were also measured. All statistical analyses were carried out with SPSS software version 13.0. We found a significant increase of all the four IgG subclass concentrations in sera of patients with RA compared to those of the controls (P < 0.001). When the patients were divided according to clinical activity, the IgG subclass concentrations were similar between the two groups (P > 0.05). Our data suggest that besides IgG1, IgG2 and IgG3, IgG4 may involve in the pathogenesis of the disease.
20050760 The platelet indices in patients with rheumatoid arthritis: mean platelet volume reflects 2010 The present study was designed to investigate the interaction between platelet indices, inflammatory markers and disease activity in rheumatoid arthritis (RA) subjects. The effects of anti-TNF-alpha therapy and conventional treatment on platelet indices were also compared. We studied 97 patients with RA (19 men, 78 women: mean age 51 years) and 33 age and sex-matched healthy subjects as a control group. All RA patients were administered conventional therapy. After 3 months of therapy, 35 subjects who had high disease activity score (DAS28 > 5.1) were grouped as non-responders and were administered infliximab as a TNF-alpha blocker at the standard intravenous dose. Responders to the conventional therapy and non-responders were also compared. At baseline white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count and mean platelet volume (MPV) were significantly higher in patients with RA. Mean platelet volume was positively correlated with DAS28 score (r = 0.27; p = 0.007). These markers of inflammation and platelet indices were substantially decreased after therapy. The reductions were similar in responders to conventional therapy and non-responders (TNF alpha group). In conclusion, we found that MPV was correlated with inflammatory markers and disease activity in patients with RA. Both anti-TNF-alpha and conventional therapy decreases markers of inflammation and platelet indices. MPV can reflect both disease activity and response to treatment.
20020140 Willingness to pay for improvement of physical function among rheumatoid arthritis patient 2011 Mar The main objective of this study was to assess the symptoms and functional difficulties caused by rheumatoid arthritis through application of the willingness to pay (WTP) method. Structured questionnaire study was conducted among 242 RA patients. The subjects were asked to evaluate their functional capacity using visual analog scales (VAS) for all the 20 questions in the Health Assessment Questionnaire (HAQ). Each VAS was followed by a question asking how much the respondent would be willing to pay on a monthly basis for a 50% improvement with the function in question. These were combined with later collected data on clinical status and use of RA-related health services. The average WTP varied greatly in the examined 20 different functions. The total WTP average on a 50% improved functional capacity amounted to 567.05 per month. Patients with lower functional capacity (HAQ 1.2 or more) were ready to contribute significantly (p < 0.001) more (705 euros/month) than those with better functional status (199 euros/month). Subjects, whose financial standing was better, reported a higher total WTP (r = 0.218, p < 0.01). On average, the total WTP of the respondents equaled 18.44% of the disposable net monthly income per person of the household. However, the variation was quite substantial. WTP among patients with rheumatoid arthritis was best depicted through the functional capacity of the patient, the possible time the patient had retired, and the global feeling of pain. In conclusion, monetary value is a concrete way of portraying subjective valuation. WTP method is suitable for assessing functional deficits of rheumatoid arthritis.
20803635 Can the application of control theory assist patient management in rheumatoid arthritis? 2010 Sep Supporting patient self-management is an important part of the care of patients with rheumatoid arthritis (RA) but patients vary in their capacity and willingness to manage their illness and may feel overwhelmed by the challenge of controlling the impact on their life. This paper discusses the value and importance of control theory and how it might be applied to enhance patients' self-management. Not only does it offer a means of identifying those who might have greatest difficulty in managing their illness, but it also points the way to effective interventions.
20233753 Biomarkers in early rheumatoid arthritis: longitudinal associations with inflammation and 2010 May OBJECTIVE: To examine associations between a panel of soluble biomarkers and progressive joint destruction assessed by magnetic resonance imaging (MRI) and conventional radiographs as well as longitudinal associations with disease activity assessed clinically and by MRI in early rheumatoid arthritis (RA) patients. METHODS: 84 early RA patients were evaluated at baseline, 3, 6 and 12 months with clinical examination, serum and urine sampling, MRI scans of the dominant wrist and conventional radiographs of the hands. A panel of biomarkers (sCTX-I, uCTX-II, sOPG, sYKL-40, sCOMP and sMMP-3) was assessed by ELISA. MRI images and conventional radiographs were scored according to the RA MRI score (RAMRIS) and the van der Heijde modified Sharp score (SHS), respectively. Longitudinal associations between biomarkers and MRI inflammation and disease activity score (DAS28) and association with the progression of damage were examined with adjustments for known predictors. RESULTS: The baseline sCTX-I level predicted progression in joint destruction assessed by MRI and conventional radiographs, whereas the uCTX-II level was a predictor of progression in SHS but not RAMRIS. Consistent associations, both with MRI inflammation (synovitis and bone marrow oedema) and DAS28 were found for sYKL-40 and sMMP-3 in addition to C-reactive protein at baseline and in longitudinal analyses. Associations remained significant in multivariate analyses. CONCLUSION: Levels of sCTX-I and uCTX-II were significant predictors of progressive joint destruction, whereas sMMP-3 and sYKL-40 were merely markers of joint inflammation. The clinical value of these markers for use in individual patients is limited due to a considerable overlap in levels of patients with progression and no progression.
20655893 Correlation of a multi-cytokine panel with clinical disease activity in patients with rheu 2010 Nov OBJECTIVE: Explore the potential use of a cytokine panel as biochemical markers of disease activity in rheumatoid arthritis (RA) patients. DESIGN AND METHODS: 57 adult RA patients were assessed using five validated clinical disease activity tools: Health Assessment Questionnaire (HAQ), standard 28-joint Disease Activity Score (DAS28), DAS28 using C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI), and Simple Disease Activity Index (SDAI). Plasma cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, TNF-α, IL1α, IL1β, MCP1, and EGF) were measured in 47 of the 57 patients and correlated with clinical indicators. RESULTS: We found significant correlations between plasma levels of IL-6 and all clinical measures of disease activity; Spearman coefficients (p values) were: HAQ: 0.347(0.017); DAS28: 0.409(0.005); DAS-CRP: 0.378(0.011); CDAI: 0.312(0.033); SDAI: 0.310(0.039); ESR: 0.448(0.002); and CRP: 0.513(0.001). IFN-γ also correlated with DAS-CRP: 0.309(0.039) and SDAI: 0.301(0.044). Furthermore, the levels of IL-6 and IFN-γ increased significantly with worsening disease, as defined by the European League Against Rheumatism (EULAR) classification of disease activity. CONCLUSION: A significant correlation between plasma levels of IL-6 and clinical disease activity in patients with RA suggests a future role of IL6 as a disease activity marker.
19348392 [The diurnal variability of blood pressure in patients with hypertension and rheumatoid ar 2009 Feb BACKGROUND: The patients with rheumatoid arthritis have high prevalence of hypertension and increased risk of cardiovascular morbidity and mortality. OBJECTIVE: To determine the level of clinical blood pressure (BP) and 24h ambulatory BP in patients with rheumatoid arthritis and hypertension. Analyze the diurnal variability of BP depending on chronic treatment with prednisone, nonsteroidal anti-inflammatory drugs and methotrexate. GROUP OF PATIENTS: 60 patients with clinically stable rheumatoid arthritis and treated or newly diagnosed hypertension. 15 male and 45 female, mean age 58 +/- 11.3 years. RESULTS: Mean clinical systolic BP 139.0 +/- 14.7 mm Hg, diastolic BP 85.7 +/- 6.5 mm Hg and heart rate 74.9 +/- 7.3 beat.min(-1). Mean 24h systolic BP 127.7 +/- 12.6 mm Hg, diastolic BP 77.7 +/- 7.4 mm Hg and heart rate 73.9 +/- 8.7 beat.min(-1). Mean clinical pulse pressure 54.7 +/- 15.6 mm Hg, mean 24h pulse pressure 50.1 +/- 11.6 mm Hg. In the whole group of patients the number of systolic dippers was 28 (47%), nondippers 17 (28%), excesive dippers 11 (18%) and risers 4 (7%), diastolic dippers 27 (45%), nondippers 9 (15%), excesive dippers 22 (37%) and risers 2 (3%). The patients treated with prednisone and nonsteroidal anti-inflammatory drugs were nondippers in 34% both for systolic BP, in 19% and 20% respectively for diastolic BP. They were excessive dippers for systolic BP in 22% and 20% respectively, for diastolic BP in 37% and 38% respectively. In the course of the treatment with methotrexate were 22% patients nondippers for systolic BP and 8% for diastolic BP, 28% was excessive dippers for systolic BP, 47% for diastolic BP. CONCLUSION: Patients with rheumatoid arthritis and hypertension have a slightly increased pulse pressure (55 mm Hg for clinical BP and 50 mm Hg for 24h ambulatory BP) in comparison to arbitrary limits in generally population. Patients treated with prednison and nonsteroidal anti-inflammatory drugs were more often nondippers (34%) in systolic BP than hypertensive control. The patients treated with methotrexate (47%), prednisone (37%) and nonsteroidal anti-inflammatory drugs (38%) were more often excessive dippers in diastolic BP than hypertensive control.
20212388 [Role of cross-sectional imaging for early diagnosis and follow-up of rheumatoid arthritis 2010 Jan Because early therapeutic intervention is effective in the management of patients with rheumatoid arthritis (RA), tools are needed for early diagnosis, prognostic evaluation and follow-up. The role of current imaging modalities, including ultrasound and magnetic resonance imaging, will be discussed.
19578278 Therapeutic and preventive effects of methotrexate on zymosan-induced arthritis in SKG mic 2009 Jun The purpose of this study was to investigate the pathology of zymosan-induced arthritis in the SKG mouse model of rheumatoid arthritis in humans, and to validate this model as a reliable drug screening system. To achieve this purpose, methotrexate (1 or 10 mg/kg, once daily) or vehicle only was administered intraperitoneally to SKG mice with zymosan-induced arthritis. Histologically, this arthritis was characterized by the presence of granulation tissue rich in granulocytes. Methotrexate suppressed the development of arthritis in ankle and wrist joints in both clinical and histological studies. These results indicated that methotrexate has not only prophylactic, but also therapeutic effects on zymosan-induced arthritis developed in SKG mice and may thus be a promising control agent for drug research in the SKG mouse model of rheumatoid arthritis.
20689443 Time to treatment in rheumatoid arthritis: factors associated with time to treatment initi 2010 Sep BACKGROUND: The importance of early diagnosis and treatment of rheumatoid arthritis (RA) is increasingly being recognized. This requires accurate triaging of suspected RA referrals from primary care and expedient assessment of these patients in secondary care. OBJECTIVES: To assess the factors associated with urgent triage for first specialist appointment and early disease modifying agents in rheumatic disease treatment. METHODS: The general practitioner (GP) referrals to a single rheumatology service from 128 new RA patients were assessed for their information content and triage allocation by the Rheumatologists. Information on symptoms, signs, and investigation results were collected. Factors associated with urgent triage allocation, time to treatment, and a GP requesting urgency were assessed. RESULTS: Median time from symptom onset to treatment was 6.1 months. Triage allocation to urgent was associated with earlier treatment (difference of 97 days, P = 0.003). GP perception of urgency (odds ratio = 13.34, 95% confidence interval: 2.20-81.02) was independently associated with an urgent triage allocation by the triaging rheumatologist. Swollen joints and a raised C-reactive protein predicted GP request for urgency. CONCLUSION: Triage is important to facilitate early treatment; however, rheumatologists in this service are not currently triaging suspected RA referrals with reference to known poor prognostic indicators. Several interventions could improve both informative referrals and triaging of referrals to decrease time to diagnosis and treatment. These interventions could include public education, GP education sessions with associated distribution of referral guidelines, and reminding triaging rheumatology clinicians about the available prognostic factors often present in GP referrals that assist with correct triage.
20812156 [Arthritis of the atlanto-axial joint with inflammatory neck pain as a primary manifestati 2010 Sep HISTORY AND ADMISSION FINDINGS: A 68-year-old woman with known degenerative joint disease suffered from increasing neck pain. Physical examination revealed painfully restricted movement of the cervical spine. INVESTIGATIONS: Erythrocyte sedimentation rate and C-reactive protein were increased. Tests for rheumatoid factors, antinuclear, anti-citrullinated protein and anti-neutrophil cytoplasmic antibody were negative. Cervical spine x-ray showed osteochondrosis with partially bridging spondylosis at C5/C6, but there was no atlanto-axial dislocation. Magnetic resonance imaging (MRI) revealed bone marrow edema and hyperintensity of the odontoid process, but there were no indications of fissures or fracture lines. TREATMENT AND COURSE: These findings indicated seronegative rheumatoid arthritis, with predominantly active atlanto-axial arthritis. After methotrexate and prednisolone had been administered the symptoms improved rapidly and inflammatory parameters returned to normal. Three months later no atlanto-axial arthritis was seen at MRI. CONCLUSION: Rheumatoid arthritis involving the atlanto-axial region should be considered in patients with persisting neck pain and signs of inflammation.
20344987 Rheumatoid arthritis. 1: Background, symptoms and ensuring prompt diagnosis and treatment. 2010 Mar 9 The first in this two part unit on rheumatoid arthritis looks at the background of the condition, its incidence and main signs and symptoms. It also discusses diagnostic criteria and investigations.