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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23413281 | The angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to rh | 2015 Mar | INTRODUCTION: The purpose of this study was to examine whether the insertion (I) and deletion (D) of angiotensin-converting enzyme (ACE) polymorphism confers susceptibility to psoriasis, vitiligo and rheumatoid arthritis (RA). MATERIALS AND METHODS: A meta-analysis was conducted on the association between the ACE I/D polymorphisms and psoriasis, vitiligo and RA. RESULTS: Fifteen studies comprising five on psoriasis, five on vitiligo and five on RA were available for the meta-analysis consisting of 2094 cases and 2871 controls. Meta-analysis of the DD+ID genotype showed significant associations with psoriasis (odds ratio (OR) 0.753, 95% confidence interval (CI) 0.601-0.921, p = 0.006). Meta-analysis showed no association between vitiligo and the ACE I/D polymorphism. Meta-analysis of the DD+ID genotype showed an association with RA (OR 2.199, 95% CI 1.379-3.506, p = 0.001). Ethnicity-specific meta-analysis of the D allele showed no association with psoriasis in Europeans, and vitiligo in South Asians. However, subgroup analysis by ethnicity revealed a significant association between the D allele and RA in Arab populations (OR 2.697, 95% CI 1.803-4.034, p = 1.3 × 10(-5)). CONCLUSIONS: Our meta-analysis demonstrates that the ACE I/D polymorphism is associated with susceptibility to RA, especially in Arab populations. | |
24932090 | The influence of vertebral fracture on the functional disability of patients with rheumato | 2014 Jun | The aim of the present study was to identify the influence of vertebral fracture (VF) on the functional disability in patients with rheumatoid arthritis (RA). This study consecutively enrolled 100 female patients aged 50 yr or older with RA. All participants underwent lateral imaging of the thoracolumbar spine by simple radiography to identify any VFs. They also completed questionnaires via interview regarding demographics, medical history, and disease outcomes including functional disability. We used univariate analysis to evaluate associations between functional disability and VF, and made multivariate logistic regression models to test independent effect of the presence of VF, the number of VFs, and the severity of VF on functional disability. Among the 100 RA patients, 47 had at least one VF, but 34 of them were asymptomatic that they had experienced a fracture. The multiple VFs ≥ 3 (OR, 8.95; 95% CI, 1.77-44.15, P = 0.01) and moderate or severe VF (OR, 3.38; 95% CI, 1.26-9.04, P = 0.02) were related to disability in univariate analysis. The multiple VFs ≥ 3 (OR, 6.13; 95% CI, 1.02-36.94, P = 0.048) was associated with functional disability of RA patients after adjusting various confounders and it was mainly in walking and arising. The VF might be an important factor which affects functional disability in RA patients. | |
24654819 | Detection of anti-cyclic citrullinated peptide using a time-resolved fluoroimmunoassay. | 2014 | In an effort to enhance the linear range of anti-CCP we developed a new immunoassay based on time-resolved fluoroimmunoassay. The precision, sensitivity, specificity, and stability of the assay were evaluated ELISA set as control. The anti-CCP IgG TRFIA kit we established had a wider detectable range than commercial ELISA ones. With regard to intra- and inter-assay precision, the TRFIA kit was better than threee commercial ELISA ones. The mean recovery rate was 101.0%. The TRFIA we developed for anti-CCP IgG detection yielded a more sensitive and reliable method for RA diagnosis and large-scale screening programs as well. | |
22562983 | Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate resp | 2013 Jan | OBJECTIVE: In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy. METHODS: Double-blind, 2-year study in which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28-erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage. RESULTS: Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28-ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant-Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively. CONCLUSION: No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients. | |
23490466 | Tissue factor expression in rheumatoid synovium: a potential role in pannus invasion of rh | 2013 Sep | Angiogenesis, as well as pannus formation within the joint, plays an important role in the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). Tissue factor (TF), an essential initiator of the extrinsic pathway of blood coagulation, is also involved in the angiogenesis and the pannus formation of RA progression. In the present study, we used immunofluorescence and confocal scanning methods to characterize TF immunolocalization in RA synovium. We showed that positive staining of TF could be immunolocalized in synoviocytes, CD19(+) B cells and CD68(+) macrophages, whereas weak or negative staining of tissue factor could be found in CD34(+) endothelial cells of neo-vessels, CD3(+) T cells and CD14(+) monocytes in RA synovium tissues. Our study demonstrates a detailed local expression of TF in the rheumatoid synovium, and supports the notion that TF, expressed not only by the synoviocytes themselves, but also the infiltrating CD19(+) B cells and CD68(+) macrophages, is involved in the pannus invasion in the progression of rheumatoid arthritis. | |
25172936 | Understanding how patients (vs physicians) approach the decision to escalate treatment: a | 2015 Feb | OBJECTIVE: We performed a qualitative study to better understand how patients with RA approach risk-benefit trade-offs inherent in the choice of remaining with their current treatment vs escalating care. METHODS: We used a think-aloud protocol to examine how patients with RA approach risk-benefit trade-offs inherent in the choice of remaining with their current treatment vs adding a biologic. The data emerging from the protocols were used to develop a conceptual model describing how patients approach the decision to escalate care. RESULTS: Participants who were strongly impacted by their disease were not open to considering alternative options. For some patients, being highly impacted by their disease results in a strong preference to escalate care. For others, the same level of distress is reason to unconditionally refuse additional medications. In contrast, those who were moderately impacted were more open to consider treatment options. Among these participants, however, subjects' risk-benefit trade-offs were consistently modified by factors unrelated to medication, including sociodemographic characteristics, role responsibilities and the quality of the patient-physician relationship. CONCLUSION: The conceptual model indicates that patients approach the decision to escalate care differently from physicians. In order to improve care in RA, it is important to recognize that many patients with moderate to high disease activity are not open to alternative treatments, which is a prerequisite to engaging in decision making. Routine clinical encounters should enable health care providers to identify these patients in order to tailor education prior to recommending treatment escalation. | |
23972958 | Clinical aspects and management of cutaneous leishmaniasis in rheumatoid patients treated | 2013 Nov | Patients under immunosuppressive therapy with tumor necrosis factor alpha (TNF-α) antagonists are vulnerable to various opportunistic infections including leishmaniasis. We present a case series of 8 travellers developing cutaneous leishmaniasis whilst on TNF-α antagonist treatment and review the literature on aspects of cutaneous leishmaniasis developing in patients treated with TNF-α antagonists. We make interim recommendations regarding the drug therapy used to maintain remission in travellers with rheumatoid disease travelling to leishmania prone areas. Despite having a medical condition requiring continued rheumatological review the interval to diagnosis appears not to be reduced compared to that described in non-rheumatoid patients. Rheumatologists and family doctors should be aware of the need for post-travel surveillance for leishmaniasis in rheumatoid patients on TNF-alpha antagonist treatment. | |
23599436 | Safety profile of protein kinase inhibitors in rheumatoid arthritis: systematic review and | 2014 May | OBJECTIVE: To summarise the adverse events (AE) reported in patients with rheumatoid arthritis (RA) treated with protein kinase inhibitors (PKi), and identify family and molecule-related AEs. METHODS: Systematic review of the PKi used in clinical trials (CTs) in RA. Medline, Embase, Cochrane Library, Web of Knowledge, and international abstracts of congress were reviewed, (up to 31 October 2012). Search was limited to interventional studies of PKi used in CTs in RA, written in English, and reporting frequencies of AE. Diseases with similar comorbidity burden also were included. Frequency of AE, serious AE (SAE), death and discontinuation due to  AEs (DCAE) were recorded. Risk of bias was assessed. Meta-analysis was carried using pooled relative risk (RR) with 95% CI as effect measure. RESULTS: The search produced 4410 hits. Forty-one articles reporting data on 21 PKi of the Janus kinase (JAK), SYK, p38 and cKit families were selected for detailed analysis. In patients treated with p38 inhibitors, RR for dizziness was 2.36 (1.20 to 4.63), and in patients treated with c-Kit inhibitors, RR for oedema was 3.43 (1.58 to 7.42). In patients treated with the JAK inhibitor tofacitinib, RR for hypercholesterolaemia was 1.70 (1.10 to 2.63) that was dose related. In patients treated with the Syk inhibitor fostamatinib, pooled RR for hypertransaminasaemia, hypertension, diarrhoea and neutropenia were 2.93 (1.02 to 8.43), 2.80 (1.58 to 5.99), 5.20 (3.19 to 8.49) and 9.24 (2.22 to 38.42), respectively. Serious infections and malignancies were not significantly more frequent in PKi-treated patients than in comparator groups. CONCLUSIONS: Event rates of serious infections and malignancies with PKi are not different from biologics. In addition, PKi have a unique safety profile related to target and off-target inhibition of kinases, at times dose related. | |
22825547 | Epstein-Barr virus and methotrexate-related CNS lymphoma in a patient with rheumatoid arth | 2013 Jul | Patients with rheumatoid arthritis (RA), especially those treated with methotrexate (MTX), might have an increased risk of lymphoproliferative disorders that are associated with Epstein-Barr virus (EBV). We describe a case of EBV-associated central nervous system (CNS) lymphoma (diffuse large B-cell lymphoma) in a patient with RA on a short course of MTX treatment. The neoplastic cells express the B-cell surface markers (CD20, Pax-5 and CD30), and EBV-encoded RNA was demonstrated by in situ hybridization. The patient's lymphoma did not recur for the 8-year follow-up period after the tumor resection and cessation of MTX. MTX may promote EBV-positive CNS lymphoma in RA patient due to its immunosuppressive properties as well as reactivating latent EBV infection. | |
24100773 | [Economic evaluation of rheumathoid arthritis monotherapy with tocilizumab and adalimumab] | 2013 Jul | BACKGROUND: Tocilizumab (TCZ) was superior to adalimumab (ADA), as monotherapy, in reducing signs and symptoms of adult rheumatoid arthritis (RA) when methotrexate (MTX) treatment is poorly tolerated or inappropriate. The aim of the study was to analyze the cost-effectiveness of TCZ vs ADA in these patients. METHODS: Economic evaluation of the cost per response or remission of TCZ vs ADA from ADACTA (time horizon: 24 weeks). Clinical response criteria ACR or disease remission criteria, DAS28. PERSPECTIVE: National Health System. The costs included (acquisition, administration and monitoring of medicines; € 2012) were obtained from Spanish sources. Simple univariate sensitivity analyzes were performed. RESULTS: ACR20, ACR50 and ACR70 response rates with TCZ and ADA were obtained in 65% and 49.4% (p <0.01), 47.2% and 27.8% (p <0.01); and 32.5% and 17.9% (p <0.01) of patients, respectively. DAS28 remission occurred in 39.9% and 10.5%, respectively (p <0.0001). The cost per response was lower with TCZ than with ADA (ACR20: € 8,105 and € 11,553; ACR50: € 11,162 and € 20,529; ACR70: € 16,211 and € 31,882) respectively. The cost of DAS28 remission was € 13,204 and € 54,352, respectively. Treatment with TCZ was dominant (more effective, with lower costs vs ADA) in all scenarios analyzed. CONCLUSIONS: According to this analysis, in Spain TCZ monotherapy is an efficient strategy vs ADA for treating RA patients intolerant to MTX or in which there is inappropriate response. | |
24293569 | Sleep problems in patients with rheumatoid arthritis. | 2014 Jan | OBJECTIVE: To investigate sleep problems, and the relationship between sleep and disease activity, in Belgian patients with established rheumatoid arthritis (RA). METHODS: This cross-sectional, observational, multicenter study assessed sleep quality using the Athens Insomnia Scale (AIS) and Pittsburgh Sleep Quality Index (PSQI), and daytime sleepiness using the Epworth Sleepiness Scale (ESS). Additional patient-reported outcomes included visual analog scales (VAS) for fatigue and pain, the Medical Outcomes Study Short Form-36 Health Survey, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Positive and Negative Affect Schedule. Multivariate regression and structural equation modeling identified factors associated with sleep quality, with the 28-joint Disease Activity Score [DAS28-C-reactive protein (CRP)] as a continuous or categorical variable. Analyses were performed on the total population and on patients stratified by disease activity status: remission/low (DAS28-CRP ≤ 3.2) or moderate to high (DAS28-CRP > 3.2). RESULTS: Among 305 patients, mean (SD) age was 57.00 (12.38) years and mean (SD) disease duration was 11.77 (9.94) years. Mean (SD) AIS, PSQI, and ESS scores were 6.8 (4.79), 7.8 (4.30), and 7.3 (4.67), respectively. Mean (SD) VAS fatigue, VAS pain, and HAQ-DI were 45.22 (26.29), 39.04 (26.21), and 1.08 (0.75), respectively. There were significant positive relationships between DAS28-CRP and AIS/PSQI, but a significant negative relationship between DAS28-CRP and ESS. Several potentially confounding factors were identified. CONCLUSIONS: Poor control of RA is associated with a reduction in sleep quality and decreased daytime sleepiness, which is likely explained by pain-related alertness. Future prospective studies are needed to confirm potential relationships between sleep quality, sleepiness, and RA treatment. | |
24811196 | Evolution of direct costs in the first years of rheumatoid arthritis: impact of early vers | 2014 | OBJECTIVES: To estimate annual direct costs of early RA by resource component in an inception cohort, with reference to four distinct treatment strategies: no disease modifying antirheumatic drugs (DMARDs), synthetic DMARDs only, biologic DMARDs in the first year ('first-year biologic', FYB), and biologic DMARDs from the second year after inclusion ('later-year biologic', LYB); to determine predictors of total and non-DMARD related costs. METHODS: The ESPOIR cohort is a French multicentric, prospective study of 813 patients with early arthritis. Data assessing RA-related resource utilisation and disease characteristics were collected at baseline, biannually during the first two years and annually thereafter. Costs predictors were determined by generalised linear mixed analyses. RESULTS: Over the 4-year follow-up, mean annual direct total costs per treatment strategy group were €3,612 for all patients and €998, €1,922, €14,791, €8,477 respectively for no DMARDs, synthetic DMARDs only, FYB and LYB users. The main predictors of higher costs were biologic use and higher Health Assessment Questionnaire (HAQ) scores at baseline. Being a biologic user led to a higher total cost (FYB Rate Ratio (RR) 7.22, [95% CI 5.59-9.31]; LYB RR 4.39, [95% CI 3.58-5.39]) compared to non-biologic users. Only LYB increased non-DMARD related costs compared to all other patients by 60%. CONCLUSIONS: FYB users incurred the highest levels of total costs, while their non-DMARD related costs remained similar to non-biologic users, possibly reflecting better RA control. | |
25536122 | Outcomes related to methotrexate dose and route of administration in patients with rheumat | 2015 Mar | OBJECTIVES: Methotrexate (MTX) is considered the 'anchor drug' in the therapy of rheumatoid arthritis (RA), yet many physicians do not optimise MTX regimens in spite of high RA disease activity. The recent development of an auto-injector for the subcutaneous (subQ) administration of MTX has prompted re-evaluation of MTX utilisation. The purpose of this systematic literature review is to determine the optimal dose, drug level, and route of administration for MTX in the context of relevant pharmacokinetics and pharmacogenomics. METHODS: A systematic literature review was performed in Medline searching specifically for randomised controlled trials, systematic reviews, case control and cohort studies evaluating outcomes related to MTX dose and route of administration. Articles fulfilling these inclusion criteria were reviewed. Data on MTX dose, route of administration, clinical response, drug levels and adverse events were evaluated. RESULTS: Our search identified 420 articles of which 6 were eligible for inclusion using the above criteria. These included 2 systematic reviews, 2 randomised open label trials, one longitudinal study and one retrospective cohort study. CONCLUSIONS: Efficacy and toxicity for MTX appear related to absorbed dose of MTX, not to route of administration. While bioavailability is greater for parenteral MTX, there is no evidence yet that splitting the oral dose of MTX is less advantageous, less safe or less tolerable than administering parenteral MTX. However, there appear to be modest benefits in beginning with higher doses of MTX, and switching to parenteral MTX when the clinical response to an oral dose is inadequate. | |
23711145 | Celastrol induced DNA damage, cell cycle arrest, and apoptosis in human rheumatoid fibrobl | 2013 | Celastrol is one of the principal active ingredients of Tripterygium wilfordii Hook.f., a toxic Chinese medical herb traditionally prescribed for controlling pain and inhibiting inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA). Resistance to apoptosis of fibroblast-like synoviocytes is considered a major characteristic of RA. In this study, we test celastrol's cytotoxic effect and potential mechanisms in human rheumatoid synovial fibroblasts (RA-FLS). In the cytotoxic assay, we found that celastrol dose-dependently decreased RA-FLS viability and increased LDH release. The apoptotic nuclear morphology was observed after celastrol treatment as determined by DAPI fluorescence staining. Flow cytometry analysis with PI and Annexin V revealed that celastrol induced RA-FLS cell cycle arrest in the G2/M phase and apoptosis. Furthermore, celastrol dramatically increased expression of Bax/Bcl-2, proteolytic cleavage of Caspase-3, -9, PARP, and decreased expression of FasR. In addition, celastrol treatment resulted in DNA damage. Collectively, we concluded that celastrol inhibits RA-FLS proliferation by inducing DNA damage, cell cycle arrest, and apoptosis in vitro, which might provide data for its application in RA treatment. | |
23266629 | Different coexpressions of arthritis-relevant genes between different body organs and diff | 2013 Feb 25 | Structural changes in different parts of the brain in rheumatoid arthritis (RA) patients have been reported. RA is not regarded as a brain disease. Body organs such as spleen and lung produce RA-relevant genes. We hypothesized that the structural changes in the brain are caused by changes of gene expression in body organs. Changes in different parts of the brain may be affected by altered gene expressions in different body organs. This study explored whether an association between gene expressions of an organ or a body part varies in different brain structures. By examining the association of the 10 most altered genes from a mouse model of spontaneous arthritis in a normal mouse population, we found two groups of gene expression patterns between five brain structures and spleen. The correlation patterns between the prefrontal cortex, nucleus accumbens, and spleen were similar, while the associations between the other three parts of the brain and spleen showed a different pattern. Among overall patterns of the associations between body organs and brain structures, spleen and lung had a similar pattern, and patterns for kidney and liver were similar. Analysis of the five additional known arthritis-relevant genes produced similar results. Analysis of 10 nonrelevant-arthritis genes did not result in a strong association of gene expression or clearly segregated patterns. Our data suggest that abnormal gene expressions in different diseased body organs may influence structural changes in different brain parts. | |
25381982 | Decrease of asymmetric dimethyl arginine after anti-TNF therapy in patients with rheumatoi | 2014 Nov | Chronic inflammatory diseases such as rheumatoid arthritis (RA) are associated with accelerated atherosclerosis and increased morbidity and mortality for cardiovascular events. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, contributes to the impairment of endothelial function, the earlier and reversible stage of atherosclerotic plaque formation. Since tumor necrosis factor (TNF) inhibits enzymatic degradation of ADMA, anti-TNF agents could restore its physiological level. The aim of this study was to investigate the effect of TNF inhibitors on ADMA serum levels in patients with RA. Our results suggest a possible effect of anti-TNF drugs on ADMA serum levels; longer studies would be necessary to confirm the role ADMA in assessing cardiovascular risk in RA. | |
25120317 | The risk of osteoporotic fractures according to the FRAX model in Korean patients with rhe | 2014 Aug | The aim of the current study is to identify patients without osteoporosis who met the criteria of the fracture risk assessment tool (FRAX) of the National Osteoporosis Foundation (NOF) only. The incidence of fractures was investigated in patients who met only the FRAX criteria of the NOF and patients who presented osteoporosis. Five hundred and forty five patients with rheumatoid arthritis who visited a single center were recruited in Korea. In the follow-up period of median 30 months, the new onset of fractures was investigated. Of 223 patients who have no osteoporosis, 39 (17.4%) satisfied the FRAX criteria for pharmacological intervention. During the follow-up period, 2 new onset fractures occurred in patients who met only the FRAX criteria and 22 new onset fractures did in patients with osteoporosis by bone mineral density. The incidence rate for new onset fractures of patients who met only the FRAX criteria was with 295.93 per 10,000 person-years higher than in the general population with 114.99 per 10,000 person-years. Patients who met the FRAX criteria of the NOF only need pharmacological intervention because their numbers of incidence for new onset fractures are similar to those of patients with osteoporosis by BMD. | |
24293568 | The OMERACT-RAMRIS rheumatoid arthritis magnetic resonance imaging joint space narrowing s | 2014 Feb | OBJECTIVE: To test the intrareader and interreader reliability of assessment of joint space narrowing (JSN) in rheumatoid arthritis (RA) wrist and metacarpophalangeal (MCP) joints on magnetic resonance imaging (MRI) and computed tomography (CT) using the newly proposed OMERACT-RAMRIS JSN scoring method, and to compare JSN assessment on MRI, CT, and radiography. METHODS: After calibration of readers, MRI and CT images of the wrist and second to fifth MCP joints from 14 patients with RA and 1 healthy control were assessed twice for JSN by 3 readers, blinded to clinical and imaging data. Radiographs were scored by the Sharp/van der Heijde method. Intraclass correlation coefficients (ICC) and smallest detectable differences (SDD) were calculated, and the performance of various simplified scores was investigated. RESULTS: Both MRI and CT showed high intrareader (ICC ≥ 0.95) and interreader (ICC ≥ 0.94) reliability for total (wrist + MCP) assessment of JSN. Agreement was generally lower for MCP joints than for wrist joints, particularly for CT. Intrareader SDD for MCP/wrist/MCP + wrist were 1.2/6.1/6.4 JSN units for MRI, while 2.7/8.3/9.9 JSN units for CT. JSN on MRI and CT correlated moderately well with corresponding radiographic JSN scores (MCP 2-5: 0.49 and 0.56; wrist areas assessed by Sharp/van der Heijde: 0.80 and 0.95), and high ICC between scores on MRI and CT were demonstrated (MCP: 0.94; wrist: 0.92; MCP + wrist: 0.92). CONCLUSION: The OMERACT-RAMRIS MRI JSN scoring system showed high intrareader and interreader reliability, and high correlation with CT scores of JSN. The suggested JSN score may, after further validation in longitudinal studies, become a useful tool in RA clinical trials. | |
22872022 | Etanercept normalises left ventricular mass in patients with rheumatoid arthritis. | 2013 Jun | BACKGROUND: Cardiovascular mortality is increased in patients with rheumatoid arthritis (RA). RA is associated with an increased left ventricular mass index (LVMI), a strong marker of cardiovascular mortality, and vessel abnormalities. Experimental studies have suggested that tumour necrosis factor α (TNFα) may induce LV hypertrophy. OBJECTIVE: To study the effect of medium-term (3- and 6-months) treatment with the TNFα inhibitor etanercept (ETN) and synthetic disease-modifying antirheumatic drugs (sDMARDs) on LV morphological features and arterial stiffness in patients with RA. METHODS: Consecutive female patients with active RA requiring treatment with ETN (n=28) or sDMARDs (n=20) were included. Clinical and biological monitoring, echocardiography and pulse wave velocity (PWV) assessment were performed at inclusion and at 3 and 6 months after the start of treatment. Paired t tests and multivariate linear regression analysis were used. RESULTS: Mean LVMI tended to be higher at baseline in the ETN group than in the sDMARD group (96.5±19.8 vs 84.3±26.8 g/m2; p=0.11 for the ETN and sDMARD groups, respectively). In patients with ETN treatment, mean LVMI was significantly decreased at 3 and 6 months (-6.3±7.6 and -14.2±9.3 g/m2; p<0.001), with no change from baseline for patients with sDMARD treatment (-2.2±10.9 and -2.7±10.2 g/m2, respectively). Blood pressure (BP) and aortic PWV were not changed by either treatment. CONCLUSIONS: ETN induced a significant decrease in LVMI with medium-term treatment with no change in BP or PWV. TNFα may be an important factor of LV hypertrophy, which may explain the benefit of TNF inhibitors on cardiovascular morbidity and mortality in RA. These results need to be confirmed by larger studies and with other TNF inhibitors. | |
22562750 | A comparative analysis of serologic parameters and oxidative stress in osteoarthritis and | 2013 Sep | In chronic diseases such as rheumatoid arthritis and osteoarthritis, the progression of the disease is characterized by stress oxidative, inflammation, and elevated levels of cholesterol. In mevalonate kinase deficiency, an auto-inflammatory disease, the correlation between inflammation and cholesterol levels is opposite. The metabolic pathway that underlies the production of cholesterol is the mevalonate pathway; it is also essential for the biosynthesis of isoprenoids involved in the control of several cell functions. This divergence of cholesterol levels, associated with these two inflammatory disorders, is probably due to a different etiology, pathogenesis, and progression. |