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ID PMID Title PublicationDate abstract
21629241 Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. 2011 May 31 The excess risk of cardiovascular disease (CVD) associated with inflammatory rheumatic diseases has long been recognized. Patients with established rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) have higher mortality compared with the general population. Over 50% of premature deaths in RA are attributable to CVD. Excess mortality in SLE follows a bimodal pattern, with the early peak predominantly a consequence of active lupus or its complications, and the later peak largely attributable to atherosclerosis. Patients with RA or SLE are also at increased risk of nonfatal ischemic heart disease. The management and outcome of myocardial infarction and congestive heart failure in patients with RA or SLE differs from that in the general population. Traditional CVD risk factors (TRF) include increasing age, male gender, smoking, hypertension, hypercholesterolemia and diabetes. Whereas some TRFs are elevated in patients with RA or SLE, several are not, and others exhibit paradoxical relationships. Risk scores developed for the general population based on TRFs are likely, therefore, to underestimate CVD risk in RA and SLE. Until additional research and disease-specific risk prediction tools are available, current evidence supports aggressive treatment of disease activity, and careful screening for and management of TRFs.
22043277 Importance of correlation between gene expression levels: application to the type I interf 2011 BACKGROUND: The analysis of gene expression data shows that many genes display similarity in their expression profiles suggesting some co-regulation. Here, we investigated the co-expression patterns in gene expression data and proposed a correlation-based research method to stratify individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using blood from rheumatoid arthritis (RA) patients, we investigated the gene expression profiles from whole blood using Affymetrix microarray technology. Co-expressed genes were analyzed by a biclustering method, followed by gene ontology analysis of the relevant biclusters. Taking the type I interferon (IFN) pathway as an example, a classification algorithm was developed from the 102 RA patients and extended to 10 systemic lupus erythematosus (SLE) patients and 100 healthy volunteers to further characterize individuals. We developed a correlation-based algorithm referred to as Classification Algorithm Based on a Biological Signature (CABS), an alternative to other approaches focused specifically on the expression levels. This algorithm applied to the expression of 35 IFN-related genes showed that the IFN signature presented a heterogeneous expression between RA, SLE and healthy controls which could reflect the level of global IFN signature activation. Moreover, the monitoring of the IFN-related genes during the anti-TNF treatment identified changes in type I IFN gene activity induced in RA patients. CONCLUSIONS: In conclusion, we have proposed an original method to analyze genes sharing an expression pattern and a biological function showing that the activation levels of a biological signature could be characterized by its overall state of correlation.
21078723 Cardiovascular disease is related to hypertension in patients with rheumatoid arthritis: a 2011 Feb OBJECTIVE: To evaluate the incidence of cardiovascular disease (CVD) among Greek patients with rheumatoid arthritis (RA) under medical followup, and to assess the contribution of traditional CVD and RA-specific factors associated with CVD development. METHODS: This is a historic cohort study; information was collected from medical records of patients who had > 2 years' followup. Sociodemographic, clinical, laboratory, and therapeutic variables were evaluated for association with development of CVD. RESULTS: A total of 325 RA patients were studied: 250 women, mean age at RA onset 44 ± 15 years, and 75 men, mean age at RA onset 51 ± 15 years; median followup was 10 years. Fourteen women (5.6%) and 12 men (16%) developed CVD (p = 0.004). Multi-adjusted analysis revealed that hypertension (hazard ratio 3.76, 95% CI 0.99-15.06) was associated with incidence of CVD; late age at disease onset (HR 1.07, 95% CI 1.04-1.11), elevated C-reactive protein (CRP) level 1 year after start of followup (HR 1.03, 95% CI 1.00-1.05), and leflunomide treatment (HR per 1 year of treatment = 1.02, 95% CI 1.00-1.05) were also positively associated with CVD development. CONCLUSION: Hypertension was an important risk factor for CVD development in patients with RA. Late RA onset and inadequate early control of disease activity (as attested by CRP) remain additional risk factors. Leflunomide treatment may have a contributing effect. Early and effective treatment of RA and strict control of hypertension may modify the burden of CVD in RA patients.
21905248 Changes in hand bone mineral density and the association with the level of disease activit 2011 Dec OBJECTIVE: To determine if metacarpal bone mineral density (mBMD) gain occurs in patients with rheumatoid arthritis (RA). If mBMD loss is driven by inflammation, we expect to find mBMD gain in patients who are in remission. METHODS: mBMD was measured by digital x-ray radiogrammetry in consecutive radiographs of 145 patients with RA with either continuous high disease activity (HDA; Disease Activity Score [DAS] >2.4), low disease activity (LDA; 1.6 ≥ DAS ≤ 2.4), or continuous clinical remission (CR; DAS <1.6) during a 1-year observation period. The association of mBMD changes with disease activity was investigated with multinomial regression analysis. Next, clinical variables associated with mBMD gain were identified. RESULTS: Mean change in mBMD in CR patients was -0.03%, compared to -3.13% and -2.03% in HDA and LDA patients, respectively (overall, P < 0.001). Of the patients in CR, 32% had mBMD loss (less than or equal to -4.6 mg/cm2/year), compared to 62% and 66% of the patients with HDA or LDA, respectively, whereas 26% of the patients in CR had mBMD gain (≥4.6 mg/cm2/year), compared to 2% of the patients with HDA and 5% of the patients with LDA. Patients in CR had a higher chance of having mBMD gain, compared with LDA and HDA (relative risk [RR] 14.9, 95% confidence interval [95% CI] 3.0-18.7 and RR 4.7, 95% CI 1.2-6.3, respectively). CR, hormone replacement therapy, and lower age were significant independent predictors of mBMD gain. CONCLUSION: In RA, mBMD gain occurs primarily in patients in continuous (≥1 year) CR and rarely in patients with continuous HDA or LDA. This suggests that mBMD loss is driven by inflammation.
21285171 Clinical consequences of delayed addition of adalimumab to methotrexate therapy over 5 yea 2011 May OBJECTIVE: This Year 5 analysis of an open-label extension (OLE) study assessed radiographic progression, clinical efficacy, and safety of adalimumab with concomitant methotrexate (MTX) for patients with active rheumatoid arthritis. METHODS: In a double-blind study (DE019, NCT00195702), inadequate responders to MTX were randomized to MTX plus either adalimumab 40 mg eow, adalimumab 20 mg weekly, or placebo for 52 weeks. Eligible patients entered an ongoing OLE and received adalimumab 40 mg eow plus MTX. Longterm efficacy and safety were evaluated. RESULTS: Of 457 patients who had enrolled in the OLE, 304 remained in the study at Year 5, including 112, 107, and 85 from the original adalimumab 40 mg, adalimumab 20 mg, and placebo groups, respectively. Year 5 radiographs demonstrated mean changes in modified total Sharp score for the original adalimumab 40 mg eow and 20 mg weekly groups of 0.8 and 2.6, respectively, versus 3.9 for placebo; 58% from the adalimumab 40 mg eow group had no radiographic progression versus 40% of those who initially received placebo. Of patients who received adalimumab 40 mg eow for 5 years, 26.1% achieved clinical remission (Disease Activity Score 28-joint count < 2.6), had no radio graphic progression (change in modified total Sharp score ≤ 0.5), and had normal function (Health Assessment Questionnaire ≤ 0.5), versus 11.9% of those who initially received placebo. Serious infection rate for 553 patients who received at least one dose of adalimumab was 4.4/100 patient-years. CONCLUSION: A 52-week delay in adding adalimumab to MTX led to worse radiographic, functional, and clinical outcomes at Year 5 for most patients who initially received placebo instead of adalimumab.
21463736 Current concepts in the management of the rheumatoid hand. 2011 Apr Hand surgeons are an integral part of the management team for patients with rheumatoid arthritis. There is now a greater understanding of the national use of rheumatoid hand surgery, which highlights the differences between hand surgeons and rheumatologists regarding the treatment of the rheumatoid hand. Advances in medical treatments have also decreased the prevalence of hand deformities caused by this disease. Hand surgeons today have less exposure to treating rheumatoid hand, but despite more effective medical options, surgery may still offer patients hope for improvement of hand function and appearance. This article summarizes the current state of rheumatoid hand surgery and discuss the surgical treatment strategies for optimizing outcomes for patients with rheumatoid arthritis.
21482840 Cost-effectiveness of adding magnetic resonance imaging to rheumatoid arthritis management 2011 Apr 11 BACKGROUND: Early, aggressive treatment of rheumatoid arthritis (RA) improves outcomes but confers increased risk. Risk stratification to target aggressive treatment of high-risk individuals with early RA is considered important to optimize outcomes while minimizing clinical and monetary costs. Some advocate the addition of magnetic resonance imaging (MRI) to standard RA risk stratification with clinical markers for patients early in the disease course. Our objective was to determine the incremental cost-effectiveness of adding MRI to standard risk stratification in early RA. METHODS: Using a decision analysis model of standard risk stratification with or without MRI, followed by escalated standard treatment protocols based on treatment response, we estimated 1-year and lifetime quality-adjusted life-years, RA-related costs, and incremental cost-effectiveness ratios (with MRI vs without MRI) for RA patients with fewer than 12 months of disease and no baseline radiographic erosions. Inputs were derived from the published literature. We assumed a societal perspective with 3.0% discounting. RESULTS: One-year and lifetime incremental cost-effectiveness ratios for adding MRI to standard testing were $204,103 and $167,783 per quality-adjusted life-year gained, respectively. In 1-way sensitivity analyses, model results were insensitive to plausible ranges for every variable except MRI specificity, which published data suggest is below the threshold for MRI cost-effectiveness. In probabilistic sensitivity analyses, most simulations produced lifetime incremental cost-effectiveness ratios in excess of $100,000 per quality-adjusted life-year gained, a commonly cited threshold. CONCLUSION: Under plausible clinical conditions, adding MRI is not cost-effective compared with standard risk stratification in early-RA patients.
21240502 Greek NHS capacity constraints regarding intravenous treatment for rheumatoid arthritis pa 2012 Apr Intravenous (iv) infusion of biologic agents is a highly effective therapeutic option for active rheumatoid arthritis (RA). In Greece, it is mandatory that all infusions are administered in a hospital setting; therefore, they are strongly correlated with the system's capacity in terms of resources. The objective of this paper was to assess the capacity of the Greek National Health System (NHS) hospitals to meet current/projected demand for iv treatment of RA patients. Semi-qualitative interviews on the basis of a strictly structured questionnaire were conducted with the Heads of all NHS RA infusion sites to record available resources, service utilization and ability to meet current/projected demand. Out of 31 NHS infusion sites, 28 responded (90.3%). On average, 41.6% of Greek NHS RA patients are treated with a biologic agent and 61.5% of respondents stated that available resources are insufficient to meet current demand. The most important constraints in selection order were as follows: space (93%), staff (89.5%), equipment (61.5%) and working hours (57%). Fifty-six percent of respondents stated that they may decline treatment to patients due to constraints. Overall, respondents estimated that the number of iv patients could be increased by 104%, were there no capacity constraints. An important proportion of the estimated 40.000 RA patients in Greece, for whom iv biologic treatment in the hospital setting is essential for disease control, may be declined treatment due to constraints in RA-specific resources. Rationalization and reallocation of NHS resources is required to ensure equity in access to effective treatment for all RA patients.
22281393 [Assessment of depression in rheumatoid arthritis: a cross sectional study on 60 patients] 2012 May OBJECTIVE: To assess the prevalence of depression in a series of Tunisian patients with rheumatoid arthritis (RA) and to identify factors associated with its occurrence. METHODS: We performed a cross sectional study on 60 patients with RA. The evaluation of depression was performed using the Montgomery and Asberg depression rating scale. RESULTS: Our study revealed a high prevalence of depression in RA patients (45%). The main predictor factors of its occurrence were female gender, absence of professional activity, absence of social support, high activity of RA, impaired quality of life and existence of structural damage. PERSPECTIVES: Our results highlight the importance of a good management of RA in order to prevent the occurrence of depression. They also underline the interest of screening for depression in RA patients to avoid its adverse effects on the course of RA.
21898075 Delayed treatment with tumor necrosis factor inhibitors in incomplete responders to synthe 2012 Apr We aimed to investigate whether delayed treatment with tumor necrosis factor (TNF) inhibitors in incomplete responders to synthetic disease-modifying anti-rheumatic drugs (DMARDs) was effective among patients with very early rheumatoid arthritis (RA) with poor prognosis factors. We examined 22 patients with very early RA who were positive for anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. The mean disease duration at entry was 14.1 weeks. A treat-to-target strategy, aiming at simplified disease activity index (SDAI) remission, was initiated with synthetic DMARDs. SDAI remission was not achieved in 9 of the 22 patients with synthetic DMARDs alone, and TNF inhibitors were added in these patients. SDAI values in these 9 patients were further examined for the following 6 months. The TNF inhibitors (infliximab 8, etanercept 1) were added at a mean interval of 34.1 weeks after the initiation of synthetic DMARDs. SDAI remission was achieved in 4 of the 9 patients (44.4%) at 3 months and in 8 of the 9 patients (88.9%) at 6 months after the introduction of the TNF inhibitors. Radiographic damage had not progressed in these patients. Delayed treatment with TNF inhibitors is effective and tolerable for patients with very early RA with poor prognosis factors.
22714601 Sweet's syndrome in a patient with rheumatoid arthritis, Sjögren's syndrome and lymph nod 2011 Feb 2 Sweet's syndrome (SS) is an acute neutrophilic dermatosis characterised by abrupt onset of fever, leukocytosis and cutaneous eruption, with dermal neutrophilia on skin biopsy. Most cases are idiopathic but SS can be associated with various affections, especially neoplastic, inflammatory and infectious diseases. The authors report the case of an SS occurring in a patient with a known rheumatoid arthritis associated with a secondary Sjögren's syndrome, with incidental finding of concurrent lymph node tuberculosis. In case of SS, an associated disease (malignant, inflammatory or infectious diseases) must imperatively be searched for, knowing that two or more of these affections can coexist.
21987483 Quantitative characterization of bone marrow edema pattern in rheumatoid arthritis using 3 2012 Jan PURPOSE: To develop imaging techniques that provide quantitative characterization of bone marrow edema pattern (BME) in wrist joints of patients with rheumatoid arthritis (RA), including volume, signal intensity changes, and perfusion properties. MATERIALS AND METHODS: Fourteen RA patients and three controls were scanned using 3 Tesla MR. BME was semi-automatically segmented in water images obtained from iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) sequences. BME perfusion parameters (enhancement and slope) were evaluated using three-dimensional (3D) dynamic enhanced MRI (DCE-MRI). Experimental reproducibility, inter- and intra-observer reproducibility of BME quantification were evaluated using root mean square coefficients of variation (RMS-CV) and intraclass correlation (ICC). RESULTS: The RMS-CV for BME volume quantification with repeated scans were 6.9%. The inter-observer ICC was 0.993 and RMS CV was 5.2%. The intra-observer ICC was 0.998 and RMS CV was 2.3%. Both maximum enhancement and slope during DCE-MRI were significantly higher in BME than in normal bone marrow (P < 0.001). No significant correlation was found between BME quantification and clinical evaluations. CONCLUSION: A highly reproducible semi-automatic method for quantifying BME lesion burden in RA was developed, which may enhance our capability of predicting disease progression and monitoring treatment response.
21245770 Vascular endothelial growth factor gene polymorphisms and rheumatoid arthritis. 2011 Mar OBJECTIVE: To investigate polymorphisms of the vascular endothelial growth factor (VEGF) gene in patients with rheumatoid arthritis (RA) and their relationship to clinical features. METHOD: A total of 198 unrelated Chinese individuals were enrolled in this study, including 98 patients with RA and 100 healthy controls. Eight different polymorphisms of the VEGF gene were analyzed using Sequenom MassArray platform. RESULT: All 8 polymorphisms were in Hardy-Weinberg equilibrium in controls. The frequencies of rs833070 A allele and rs325010 C allele were elevated in the patients with RA compared with the controls. There were increased genotype frequencies in GA of rs833070, GC of rs3025030, CT of rs3025039 and decreased genotype frequencies in GG of rs833070, GG of rs3025030, CC of rs3025039 in the patients with RA compared with the controls. The frequencies of haplotype GA in rs2010963 and rs833070 were higher in the patients with RA than in the controls. There was no significant difference in the genotype or allele frequencies in the RA group sorted by complications, serum markers, or age of onset. CONCLUSION: Our data suggested a trend of association between VEGF gene polymorphisms and RA, and patients who carried the haplotype GA of rs2010963 and rs833070 were more susceptible to RA. Our study was performed in a small population, and further studies in other populations are needed to confirm these results.
22476205 Quality of life of patients with rheumatoid arthritis in Argentina: reliability, validity, 2012 Jul The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is the first needs-based instrument specifically designed to measure quality of life (QoL) of patients with rheumatoid arthritis (RA). The aims of our study were to develop an Argentinean version of the RAQoL and to determine its reproducibility, validity, and sensitivity to change in patients with RA. Translation process was performed according to internationally accepted methodology. Internal consistency and test-retest reliability were calculated. Criterion and construct validity were assessed by comparing the RAQoL with parameters of disease activity, the Health Assessment Questionnaire (HAQ), and the Medical Outcomes Study 36-item health survey (SF-36) questionnaire. Sensitivity to change was measured at 6-12 months using standardized response mean (SRM). The minimal important change was defined as a change of 1 or 1.96 times the standard error of measurement. A total of 97 patients with RA were included. Cronbach's α was 0.93, and test-retest reliability was 0.95. The RAQoL showed moderate to strong correlation with parameters of disease activity, the HAQ, and the SF-36. Functional status was the main determinant of patients' level of QoL. The SRM of the RAQoL was 0.24. Agreement between 20 % improvement in RAQoL and ACR20 response was moderate. Minimal important change was 2.2 (1 SEM) or 4.3 (1.96 SEM). The Argentinean version of the RAQoL is the first Spanish translation of this questionnaire. Our findings show it to be valid, reliable, and sensitive to changes in RA clinical status.
22623274 HLA-DRβ1*04 typing by simple in-house PCR-SSP technique for rheumatoid arthritis patients 2013 Apr A strong association between rheumatoid arthritis (RA) and human leukocyte antigen (HLA) has been observed in many different populations and that accounts for approximately one-third of the genetic component of RA susceptibility. The greatest effect comes from DRβ1 gene where the strongest association has been found with DRβ1*04 (DR4) allele. As serology has some disadvantages over polymerase chain reaction (PCR)-based techniques and commercially available PCR-based kits are expensive, this study was aimed to standardize simple in-house PCR-SSP technique. Accuracy of this test was further checked with standard PCR-SSOP (RLS) results. The frequency HLA-DRβ1*04 was significantly increased among RA patients when compared with normal controls. In this study, a very simple, convenient and more cost-effective in-house PCR-SSP technique was standardized for HLA-DRβ1*04 typing that is helpful to RA diagnosis in developing countries like India, which can be used as a good screening test.
22214810 The effects of disease modifying anti-rheumatic drugs on osteoclastogenesis and bone destr 2011 Finding the means to ameliorate and prevent bone destruction as well as control inflammation is an urgent issue in the treatment of rheumatoid arthritis (RA). Recently, it has been demonstrated that osteoclastogenesis plays an important role in the bone destruction and pathogenesis of RA. Here, we review the effects of disease modifying anti-rheumatic drugs (DMRAD) on the amelioration of bone destruction and osteoclastogenesis.
22419152 Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by usi 2012 Apr Rheumatoid arthritis (RA) is the most severe type of chronic inflammatory disease and has always been a research hotspot in different fields. In this study, a non-targeted metabonomics approach was carried out to profile metabolic characteristics of RA and its Chinese medicine subtypes by using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Plasma samples of 57 RA patients and 23 healthy controls were collected. On the basis of the traditional Chinese medicine (TCM), RA patients were classified into two main patterns, the cold pattern and the heat pattern. By using univariate and multivariate data analysis, we found that the RA patients presented diverse dysfunctions in inositol phosphate metabolism, lipid metabolism, amino acid metabolism, glucose metabolism, ascorbate metabolism, glyoxylate and dicarboxylate metabolism. The metabolic phenotypes were different between the RA cold pattern and the RA heat pattern. Compared with the RA cold pattern, the RA heat pattern showed elevated plasma concentrations of glycochenodeoxycholate, proline, saturated and mono-unsaturated phosphatidylcholine (PC) but decreased levels of urea, free fatty acid (FFA) and polyunsaturated PC. Our data show that metabonomics is a valuable tool in disease and TCM subtype research.
20480164 A fatal case of acute exacerbation of interstitial lung disease in a patient with rheumato 2012 Dec A 68-year-old man, who was a patient with established rheumatoid arthritis (RA) with RA-associated interstitial lung disease (RA-ILD) and pulmonary emphysema, began taking tocilizumab. Subsequently, he developed dyspnea parallel to improvement of RA. At 10 months after the administration of tocilizumab, he was urgently admitted because of exacerbation of ILD. He died despite receiving steroid pulse therapy and antibiotic therapy on a respirator. This is the first case report to describe the exacerbation of ILD during treatment with tocilizumab in the postmarketing surveillance (PMS) period.
23171316 Associations of the IL-1F7 gene polymorphisms with rheumatoid arthritis in Chinese Han pop 2013 Jun Our aim was to investigate whether genetic polymorphism of IL-1F7 (rs3811047) was involved in the susceptibility to rheumatoid arthritis (RA) in Chinese Han population. Single nucleotide polymorphism (SNP) of IL-1F7 gene (rs3811047) was analyzed in 184 unrelated Chinese Han patients with RA and 184 healthy controls by ligase detection reaction based on high temperature ligase detection reactions polymerase chain reaction (LDR-PCR). There were no statistically significant differences in the genetic polymorphism (genotypes and allele frequencies) of IL-1F7 (rs3811047) in the patients with RA compared with control. Although all of the clinical and laboratory measures were similar to each other among patients with different genotypes, RA patients carrying AA or AG genotypes had lower swollen joint count, swollen joint index, rest pain and health assessment questionnaire (HAQ) score than that in patients having GG genotype (P < 0.05). These findings show that no evidence for the involvement of a pro-inflammatory polymorphism in the IL-1F7 in the susceptibility to RA in China. Patients carrying A allele had less severe disease activity than those not carrying this allele, suggesting that the A allele of IL-1F7 gene (rs3811047) may have a protective effect on RA.
21965642 The influence of the definition of patient global assessment in assessment of disease acti 2011 Nov OBJECTIVE: Patient global assessment (PGA) is one of the 4 items included in the Disease Activity Score (DAS28) for evaluation of activity of rheumatoid arthritis (RA). We studied the influence of the use of 3 different techniques of PGA on the assessment of disease activity. METHODS: We evaluated 3 different DAS28 according to the technique of PGA in 108 patients with active RA before and after 12 weeks of etanercept therapy. RESULTS: The reliability (intraclass coefficient of correlation) between screening and baseline was very high and similar for the 3 DAS28. The percentage of patients in the different states of disease (from remission to higher disease activity) and the sensitivity to change across the 3 DAS28 scales were very similar. CONCLUSION: The different techniques of collection of PGA to be included in the DAS calculation yield similar results. However, an accepted, unequivocal technique should be encouraged in order to reduce heterogeneity in scoring DAS among patients with RA.