Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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22111893 | Illness perceptions account for variation in positive outlook as well as psychological dis | 2012 | Psychological distress in rheumatoid arthritis (RA) is associated with adverse clinical outcomes, and appears highly related to patients' illness perceptions. This study aimed to investigate the association between illness perceptions, psychological distress, positive outlook and physical outcomes in RA. Two hundred and thirty patients aged >18 years and prescribed at least one disease-modifying anti-rheumatic drug (DMARD) were recruited from outpatient clinics across Hertfordshire (England). Patients completed a questionnaire that assessed psychological distress and positive outlook (depression, anxiety and positive outlook scale), illness perceptions (IPQ-R) and functional disability (health assessment questionnaire). Information regarding prescribed medication and disease activity [disease activity score (DAS28)] was collected from medical notes. Psychological distress, but not positive outlook, was associated with functional disability and DAS28. After controlling for sex, age and DAS28, perceptions of greater symptomatology (identity) and lesser understanding of RA (coherence) were significantly associated with increased psychological distress. Perceptions of greater treatment control were associated with greater positive outlook, but only for those with low DAS28. Coherence was also associated with positive outlook. These findings indicate that illness perceptions may influence psychological distress and positive outlook in RA patients, and may therefore be a useful basis for future psychological interventions. | |
22131049 | Metrologic properties of ultrasound versus clinical evaluation of synovitis in rheumatoid | 2012 Apr | OBJECTIVE: To evaluate the intraobserver reliability, face validity, and discriminant capacity of different global ultrasound (US) scoring systems for measuring synovitis in rheumatoid arthritis (RA). METHODS: This study was ancillary to a 52-week, multicenter, prospective, randomized, open-label, parallel-group outpatient study conducted in patients with moderate RA who were randomized to receive either etanercept combined with methotrexate or various disease-modifying antirheumatic drugs. A total of 66 different synovitis scoring systems were constructed and evaluated, including 11 different joint combinations; data derived from clinical findings, gray-scale US, and power Doppler US (PDUS); and both binary counts and semiquantitative scores. RESULTS: Due to discontinuation of the trial, only 62 patients, a subset of the initially planned number of patients, were included in this study. Reliability was found to be better for gray-scale US and PDUS than for clinical evaluation of synovitis in patients with stable disease between the screening and baseline visits (range for intraclass correlation coefficient 0.6, 0.95 for gray-scale US and 0.56, 0.93 for PDUS versus 0.31, 0.75 for clinical indices). The median (range) difference in the discriminant capacities of clinical indices versus gray-scale US and versus PDUS was 0.25 (-0.64, 0.96) and -0.025 (-0.59, 0.53), respectively, in the period from baseline to 12 weeks. No relevant differences in metrologic properties were observed regarding the number and composition of joints between the different scoring systems. Our findings suggested that a simplified scoring system referring to gray-scale US and PDUS findings might be sufficient. CONCLUSION: Our findings indicate that gray-scale US and PDUS have better reliability than generally used clinical indices for evaluating synovitis in RA. PDUS has at least as good discriminant capacity as clinical assessment of synovitis for distinguishing between treatment arms. | |
21953344 | Subclinical renal dysfunction is independently associated with cardiovascular events in rh | 2012 Mar | BACKGROUND: Patients with rheumatoid arthritis (RA) have double the risk of cardiovascular (CV) disease, largely independently of traditional CV risk factors. Renal dysfunction is associated with CV morbidity and mortality in the general population, but data on this association in RA are lacking. OBJECTIVE: To investigate the association between renal function and CV events in RA. METHODS: The CARRÉ Study is an ongoing prospective cohort study of Dutch patients with RA, which records CV events. Glomerular filtration rate (GFR) was estimated with the abbreviated Modification of Diet in Renal Disease formula. Logistic regression determined the association between estimated GFR and the occurrence of CV events. RESULTS: 353 patients were followed for 3 years, and 23 (7%) had a CV event. Patients who had an event had a significantly lower baseline GFR than those who did not (59 vs 79 ml/min, p=0.001). This association remained significant after adjustment for traditional risk factors: in this analysis, a decrease in GFR of 5 ml/min was associated with a 30% (95% CI 7% to 59%) increase in the occurrence of CV events. During follow-up, an unfavourable change in GFR was noted in patients who later had a CV event compared with those who did not. CONCLUSION: These data confirm that, in RA, renal dysfunction is associated with a higher risk of CV disease independently of traditional CV risk factors. | |
21773884 | Methylenetetrahydrofolate reductase polymorphisms, C677T and A1298C, are associated with m | 2012 Jun | We investigated associations between the methylenetetrahydrofolate reductase (MTHFR) polymorphisms C677T and A1298C and methotrexate (MTX)-related toxicities in Korean patients with rheumatoid arthritis (RA) taking MTX. One hundred sixty-seven patients with RA were enrolled in a cross-sectional study and genotyped for the single-nucleotide polymorphisms C677T and A1298C in MTHFR. Alleles, genotypes, and haplotypes of the C677T and A1298C polymorphisms were not associated with specific MTX toxicities. However, among RA patients with the 1298CC genotype, the proportion who experienced at least one toxicity was significantly greater than the proportion of patients with 1298AA who did (P = 0.043). In addition, the proportion of patients with the 677C/1298A haplotype who experienced toxicity was greater than the proportion of those with 677C/1298C who did (P = 0.032, odds ratio = 2.085, 95% confidence interval 1.058-4.106). In this study, MTHFR polymorphisms were associated with MTX toxicities in Korean patients with RA. Further study for association of MTHFR polymorphisms with MTX toxicities should be needed in larger RA population. | |
22532630 | Rapid radiological progression in the first year of early rheumatoid arthritis is predicti | 2012 Sep | OBJECTIVE: Several prediction models for rapid radiological progression (RRP) in the first year of rheumatoid arthritis have been designed to aid rheumatologists in their choice of initial treatment. The association was assessed between RRP and disability and joint damage progression in 8 years. METHODS: Patients from the BeSt cohort were used. RRP was defined as an increase of ≥5 points in the Sharp/van der Heijde score (SHS) in year 1. Functional ability over 8 years, measured with the health assessment questionnaire (HAQ), was compared for patients with and without RRP using linear mixed models. Joint damage progression from years 1 to 8 was compared using logistic regression analyses. RESULTS: RRP was observed in 102/465 patients. Over 8 years, patients with RRP had worse functional ability: difference in HAQ score 0.21 (0.14 after adjustment for disease activity score (over time)). RRP was associated with joint damage progression ≥25 points in SHS in years 1-8: OR 4.6. CONCLUSION: RRP in year 1 is a predictor of worse functional ability over 8 years, independent of baseline joint damage and disease activity. Patients with RRP have more joint damage progression in subsequent years. RRP is thus a relevant outcome on which to base the initial treatment decision. | |
21253736 | Clinical and magnetic resonance imaging findings of the temporomandibular joint and mastic | 2012 May | The aim of this study was to investigate the clinical, radiographic, and magnetic resonance imaging (MRI) findings of temporomandibular joint (TMJ) and masticatory muscles in rheumatoid arthritis (RA) patients. Twenty-eight RA patients and 29 healthy subjects were participated in the study. The patient underwent clinical and laboratory investigation. DAS28 scores were calculated. Lateral panoramic radiography was performed to evaluate condylar erosion and condylar movement. Craniofacial MRI was performed to evaluate TMJ and masseter, medial and lateral pterygoid muscles' thickness, and cross-sectional area. It was found that the mean maximal interincisal distance, range of lateral, retrusive (P < 0.05) and protrusive motion were all lesser in RA group. Lateral panoramic radiography revealed a distinct erosion in 10.7% (3/28) and restricted condylar movement in 53.6% (15/28) of RA patients. Two RA patients demonstrating marked condylar erosion in lateral panoramic radiographs were RF negative and had DAS28 scores 3.41 and 4.61. MRI findings revealed condylar erosion and effusion in one RA patient and atrophic changes of masticatory muscles in another patient. There was no statistical significance between RA and healthy groups for the thickness and cross-sectional areas of the masticatory muscles. RA group revealed a strong linear relationship for the right and left muscle thickness and cross-sectional areas in regression analysis. TMJ symptoms are frequent findings and thought to be affected from mean disease duration in RA. Laboratory findings should be considered for disease activity-related TMJ involvement. RA patients did not present muscular atrophy or hypertrophy. | |
21283144 | Sexual dimorphism of RA manifestations: genes, hormones and behavior. | 2011 May | Women are more likely than men to develop rheumatoid arthritis (RA), and recent data suggest that they also suffer greater disability than men with this disease. The reasons for these sexually dimorphic patterns of disease incidence and progression are unknown, but investigations into the underlying mechanisms could provide useful insights into RA pathogenesis and may also suggest new treatment approaches. The processes of sexual differentiation involve genetic input, gonadal hormone signaling and responses from target cells and tissues. Layered upon these processes are behavioral characteristics of males and females acquired as a result of their social context. Differences in disease presentation between the sexes could be the result of complex combinations of all these factors. Recent research suggests that the developmental processes of sexual differentiation might render women more susceptible than men to similar levels of immune or inflammatory burden by virtue of sex-specific differences in body composition and structure. | |
22562979 | After treat-to-target: can a targeted ultrasound initiative improve RA outcomes? | 2012 Jun | For patients with rheumatoid arthritis (RA), remission can be achieved with tight control of inflammation and early use of disease modifying agents. The importance of remission as an outcome has been recently highlighted by European League Against Rheumatism recommendations. However, remission when defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who have recently formed a research network--the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted ultrasound in RA. | |
26856043 | PREVALENCE OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN PATIENTS CLASSIFIED AS RHEUM | 2012 Jun | BACKGROUND: Rheumatoid arthritis(RA) is a debilitating condition.Early diagnosis of RA can be difficult as the disease may initially be indistinguishable from Undifferentiated arthritis(UA). American College of Rheumatology criteria(ACR)is not suitable for early diagnosis as its characteristics are fulfilled when bone damage has already taken place.Anti-cyclic citrullinated antibodies(Anti-CCP) are highly specific for RA and have been used to confirm early diagnosis. OBJECTIVE: To determine the prevalence and clinical utility of Anti-CCP antibodies in patients with rheumatoid and undifferentiated arthritis at presentation to KNH medical clinics. Design: A cross-sectional descriptive study. SETTING: Kenyatta National Hospital Medical Outpatient Clinics (MOPCs) between the month of October 2008 to February 2009. RESULTS: A total of 95 patients were recruited.The mean age of the patients studied in the RA and UA was 44.7 and 41.2(p=0.356) respectively. Sixty four patients(64) satisfied ACR criteria.The overall prevalence of Anti-ccp antibodies in the population studied was 47.4%.The prevalence of Anti-ccp antibodies in patients who satisfied the ACR criteria was 62.5%.The prevalence of Rheumatoid Factor (RF) in patients who satisfied the ACR criteria was 50% compared to 9.7% for those who did not(p=0.000). The male to female ratio of subjects studied was 1:11. CONCLUSION: Anti-ccp antibodies are more prevalent in this cohort of patients with rheumatoid and undifferentiated arthritis than RF It was also concluded that ACR characteristics correlated well with Anti-ccp and RF. A greater percentage of patients who were RF negative were Anti-ccp positive. | |
22265261 | Adaptive immunity in rheumatic diseases: bystander or pathogenic player? | 2011 Dec | Rheumatic diseases comprise a wide spectrum of different conditions. Some are caused by disturbances of the adaptive immune system, while defects in innate immune responses have been identified for others. In between are a variety of multifactorial diseases for which the evidence for a causative involvement of the adaptive immune system is still controversial. In these cases, availability of novel drugs that target key players of the adaptive immune system have improved our understanding of the relevance of adaptive immunity to the disease process, but it has also generated unprecedented findings. Rheumatoid arthritis (RA) is a prototypic example of a disease in which the relative contribution of adaptive immunity to disease pathogenesis is incompletely understood. Although numerous markers have been identified that reflect an activated adaptive immune system, several caveats render interpretation of these findings difficult. For one, the very early immune responses initiating disease are likely to take place before an individual is identified as a patient, and are thus difficult to study in the human. Furthermore, increasing evidence points to pathogenetically distinct subgroups within the clinical diagnosis RA, offering the possibility that adaptive immune responses might be relevant to one subgroup but not the other. In addition, many indications for an adaptive immune system involvement are based on associations for which the underlying mechanism is often unknown. Finally, therapeutic interventions targeting the adaptive immune system have generated heterogeneous results. The present review addresses these issues by placing adaptive immune responses in the context of rheumatic diseases, and by reviewing the evidence for a contribution of adaptive immunity to RA. | |
20049446 | Comparison of the second and third generation anti-cyclic citrullinated peptide antibody a | 2011 May | The anti-cyclic citrullinated peptide (CCP) antibody has become increasingly important in the diagnosis of rheumatoid arthritis (RA), especially for early diagnosis. The purpose of this study is to compare the diagnostic usefulness of the second and third generation anti-CCP antibody kits among Japanese patients with RA. Anti-CCP antibody titers were measured with the second generation (MESACUP CCP test, Medical and biological laboratories) and third generation (QUANTA Lite CCP3 IgG ELISA, Inova Diagnostics) kits using serum samples from 106 rheumatoid arthritis (RA) patients and 57 non-RA patients. Sensitivities and specificities were compared. The sensitivity and specificity of the second generation anti-CCP (anti-CCP2) kit were 88.7 and 89.5%, and those of the third generation anti-CCP (anti-CCP3) kit were 91.5 and 87.7%. Area under the receiver operating curve showed that anti-CCP2 and anti-CCP3 had similar diagnostic performances. Diagnostic performance of the anti-CCP3 assay was comparable with the anti-CCP2 assay in Japanese patients with RA. | |
21947181 | Impaired postural control is associated with worse scores of the Health Assessment Questio | 2011 Oct | OBJECTIVE: To explore the relationship between functional status and different domains of postural control, and to make recommendations about the use of postural control tests in clinical practice among women with rheumatoid arthritis. SUBJECTS: A total of 91 women with rheumatoid arthritis and 110 controls. The patients were grouped according to the total score of the Health Assessment Questionnaire (HAQ):HAQ1 = 0 (good, n = 21); HAQ2 = 0.1 to < 1 (impaired, n = 44);HAQ3 = 1–3 (severely impaired, n = 26). METHODS: Postural control tests: timed one-leg stance test(OLST), timed up and go test (TUG), and posturography tests on a force-plate. RESULTS: A poorer performance in the OLST and TUG tests was associated with higher, i.e. worse, HAQ scores. The results of the force-plate measurements were more complex.The results for healthy controls provided some clarifying information,but did not alter the main results. CONCLUSION: It is recommended that both OLST and TUG tests are included in the postural control assessment design for patients with arthritis. It seems that the force-plate measurements are not as good for screening postural control impairments associated with functional disability, but they may still have their use in, for example, monitoring the effect of intervention or rehabilitation. | |
22661552 | Evidence of the symptomatic and structural efficacy of methotrexate in daily practice as t | 2012 Sep | OBJECTIVE: To describe the use of MTX in early arthritis (EA) in daily clinical practice and to evaluate its 6-month symptomatic efficacy and 12-month structural efficacy. METHODS: Patients included in the French observational ESPOIR cohort were assessed. Evaluation of the symptomatic and structural efficacy was performed by generalized linear regression after adjustment on propensity score (PS) in the group of patients receiving at least 3 months of MTX vs the ones receiving any other treatment except LEF, SSZ or TNF inhibitors. RESULTS: Within the first 6 months of follow-up of 777 EA patients, 59% received a DMARD, which was MTX in 68% (N = 313) of patients. The mean dose of MTX was 12.7 ± 3.8 mg/week. Only 53.7% of the patients received folic acid supplementation. MTX was initiated in patients with more active and severe disease. At 6 months, in unadjusted analysis, patients starting MTX had a significantly higher DAS-28 (3.58 vs 3.23; P = 0.001) and a significantly higher HAQ (0.60 vs. 0.48; P = 0.01) compared with controls. After adjustment by PS, there were no significant differences. Adjustment for the PS also revealed a statistically significant decrease in the radiological progression at 12 months in the MTX group [total Sharp-van der Heijde score (SHS), 1.05 ± 0.29 vs 2.02 ± 0.29, P = 0.025]. CONCLUSION: This study confirms the symptomatic and structural efficacy of MTX in EA in daily practice despite the non-optimal use of MTX, including low doses and infrequent concomitant folic acid supplementation. | |
21210359 | [miRNA in epigenetics of rheumatic diseases]. | 2011 Jan 5 | Epigenetic modifications are heritable changes in genome function that occur without a change in DNA sequence. They turn genes on or off by small chemical modifications. Thereby, they change the structure of the DNA making them accessible or not for transcription factors or other DNA binding molecules. MicroRNAs are a new class of regulatory non-coding RNAs that modulate gene expression and influences epigenetic mechanisms. miRNAs offer novel mechanisms of therapeutic strategies for cancer and autoimmune diseases. Here, we summarize which miRNAs play a role in rheumatic diseases and their biological function. | |
23013848 | Occurrence of rheumatoid arthritis requiring oral and/or biological disease-modifying anti | 2012 Oct | We report 6 patients with an established diagnosis of primary Sjögren syndrome who developed severe rheumatoid arthritis (RA) requiring oral disease-modifying antirheumatic drug with or without biologic therapy. Rheumatoid arthritis was diagnosed between 14 months and 17 years following initial sicca symptoms. Five patients were female. Two thirds were seropositive for Sjögren antibody, and 5 of 6 were either rheumatoid factor or anti-cyclic citrullinated peptide positive at the time of RA diagnosis. All had either hand or wrist involvement; one third had nodules. Although none demonstrated erosion on x-ray, all required methotrexate or leflunomide, and 4 required a biologic agent for the treatment of their arthritis. Primary Sjögren patients may develop RA after a long course of stable Sjögren. | |
20798264 | The complexity of the treatment: the decision-making process among women with rheumatoid a | 2011 Feb | There are effective medications available for the treatment of rheumatoid arthritis (RA); yet, medication adherence remains a problem. In this study, grounded theory methodology was used to investigate the decision-making process used by 30 women with RA when deciding to participate in an evidence-based treatment regimen for this disease. From the study findings, a four-phase process was identified. Pain, life functioning, and exhaustion of health care resources are the components of the initial phase, decision initiation. During knowledge acquisition, the second phase, patients attain information about RA and medications used for its treatment from varying sources. The third phase, trusting the health care provider, is defined by a trusting relationship between patients and health care providers. Patients decide to take or not take medications for RA during the final phase, decision is made. The participating women with RA used a complex decision-making process when deciding to take medications for this disease. | |
21889771 | Lack of association between IL6 single nucleotide polymorphisms and cardiovascular disease | 2011 Dec | INTRODUCTION: Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis. IL-6 is a key mediator of inflammation in RA. A recent study showed an association between IL6-174 G/C gene polymorphism and cardiovascular (CV) disease in UK individuals with RA. To confirm this association we assessed the influence of three IL6 gene polymorphisms in the risk of CV disease in a large series of patients with RA. MATERIAL AND METHODS: We studied 1250 Spanish patients with RA. Besides genotyping the traditional single nucleotide polymorphism (SNP) promoter -174G/C (rs1800795), we assessed another two SNPs (rs2069827 and rs2069840) located in the IL6 gene that were selected by SNP-tagging. RESULTS: Two-hundred and twenty (17.6%) of the 1250 patients experienced CV events. No significant differences in the genotype, allele and haplotype frequencies between RA patients with and without CV events were observed. CONCLUSION: Our results do not confirm in a Spanish population the association of IL6 gene with CV disease in RA previously reported in the UK. | |
22794095 | Taking advances from bench to bedside during the last decade. | 2012 Apr | The remarkable advances in understanding the pathogenesis and therapeutic options for rheumatoid arthritis over the last 10 years are a leap forward in the treatment of this disease. This has led to a shift in focus from established disease to early identification and treatment. Actualisation of treatment guidelines aiming for remission, and a vastly growing arsenal of new synthetic and biological agents have been major achievements. An area of ongoing research is the discovery and development of additional and improved biomarkers for (early) disease with the goal of designing a more personalised treatment regimen to prevent structural tissue damage. Developing valid tools to predict response and outcome for the individual patient remains, however, a great challenge. We will herein summarise some of the major achievements in diagnostic and therapeutic discoveries in rheumatoid arthritis of the past decade. | |
21807793 | OMERACT 10 Patient Perspective Virtual Campus: valuing health; measuring outcomes in rheum | 2011 Aug | This workshop reviewed progress in a number of areas related to patient perspective outcomes that were not specifically included within other areas of the program. A substantial review of the work of the valuing health outcomes group (the "QALY" working group) with participation and feedback from the plenary audience resulted in guidance to refocus on the use of patient preferences in the elaboration of more robust outcome measures for patient-reported outcomes and life impact measures. Progress and developments in the areas of fatigue and sleep in rheumatoid arthritis, outcome measures in hip and knee arthroplasty clinical trials, and scleroderma were outlined, and the challenge of truly understanding the nature of clinically important improvement was reviewed. | |
22898218 | Comparison of expectations of physicians and patients with rheumatoid arthritis for rheuma | 2012 Aug | AIM: To describe and compare expectations of patients with rheumatoid arthritis (RA) and their physicians with regard to what is most important to achieve during a rheumatology clinic visit. METHODS: Subjects were RA patients enrolled in four centers from China, one from Japan and one from the USA, and rheumatologists at those centers. The questionnaires were provided at clinics and patients were asked to list their three top priorities for the rheumatology clinic visit. Physicians were contacted separately and asked to give three general expectations, not for specific visits. We classified clinical expectations into a series of 24 terms for patients and 17 for physicians. We compared physicians' to patients' responses, compared expectations among centers in China, Japan and the USA, and evaluated relationships between patients' responses and age, gender, nationality, disease duration and DAS-28 (Disease Activity Score-28). RESULTS: Patients' clinical expectations for visits focused primarily on control of pain (63.7%), improvement of function (49.3%) and discussion of effects of medication (38.1%). Physicians also included control of pain (59.5%), but also emphasized inquiry about drug side-effects (47.8%) and objective assessment of disease activity (41.4%). We found no differences related to patients' gender, disease duration and DAS-28, but there were some differences related to age and nationality. CONCLUSION: We found some agreement and some discordance of clinical expectations between RA patients and physicians. There appear to be some different expectations in different countries. Findings from this pilot survey may help physicians consider patients' expectations in planning rheumatology clinic visits and may lead to further hypothesis-driven studies. |