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ID PMID Title PublicationDate abstract
20934962 Blood serum levels of amino-terminal pro-C-type natriuretic peptide in patients with rheum 2010 PURPOSE: Angiogenesis is a prominent feature of rheumatoid synovitis and contributes to perpetuation of joint disease. The aim of presented study was to evaluate the association of inflammatory response and endothelial dysfunction parameters with serum levels of amino-terminal pro-C-type natriuretic peptide (NT-proCNP), a surrogate measure for a potent regulator of vascular tone and angiogenesis, CNP. MATERIAL/METHODS: We included in this study 40 rheumatoid arthritis (RA) patients (36 female, four male) and 30 healthy controls (28 female, two male). Disease activity score (DAS28), Health Assessment Questionnaire Disability Index (HAQDI), Rheumatoid Arthritis Disease Activity Index (RADAI) and visual analogue scales (VAS) for pain and arthritis were determined. The concentrations of the following laboratory parameters (serum C-reactive protein (CRP), soluble (s) L-, sP-, sE-selectin, NT-proCNP, IgM rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies) were measured using sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentrations of NT-proCNP in RA patients were significantly increased when compared to healthy controls (p<0.001). In RA patients we found significant correlations only between sE-selectin and NT-proCNP levels (p=0.02). No significant associations were found between serum NT-proCNP and soluble selectin levels and patients' age and sex. Also, the parameters of clinical profile in the RA group (HAQ, RADAI, DAS28, VAS-pain, VAS-arthritis, swollen and tender joint counts) showed no association with serum NT-proCNP, sE-, sP- and sL-selectin. CONCLUSIONS: Serum concentration of NT-proCNP reflecting serum CNP level is likely secondary to the activation of endothelium. Nevertheless, the results of our study encourage to further studies over the role of CNP in the pathogenesis of RA, preferably on tissue level.
20516019 ADAMTS5 is a biomarker for prediction of response to infliximab in patients with rheumatoi 2010 Jul OBJECTIVE: To identify a biomarker for prediction of the response to infliximab (IFX) in patients with rheumatoid arthritis (RA), we focused on a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) that seems to play a key role in aggrecan degradation in cartilage. METHODS: Seventy-three randomly selected patients with active RA were treated with IFX. Peripheral blood samples were collected at baseline and ADAMTS5 messenger RNA (mRNA) was quantified using real-time polymerase chain reaction. RESULTS: Baseline ADAMTS5 mRNA levels in the good responder group were significantly lower (1.84 +/- 1.56; p = 0.0408) than those in the moderate and nonresponder groups (2.54 +/- 1.70) at 38 weeks of treatment with IFX. The 28-joint count Disease Activity Score (DAS28) at 38 weeks of treatment was significantly lower in the low ADAMTS5 group (2.30 +/- 1.28; p = 0.0038) than in the high ADAMTS5 group (3.90 +/- 1.61). The percentage reduction of the DAS28 was significantly higher in the low ADAMTS5 group (52.5% +/- 28.8%; p = 0.0156) than in the high ADAMTS5 group (29.4% +/- 27.2%). Further, the Delta Health Assessment Questionnaire (DeltaHAQ) score, an estimate of the improvement in the HAQ score, at 38 weeks of treatment was significantly higher in the low ADAMTS5 group (1.18 +/- 0.60; p = 0.0102) than in the high ADAMTS5 group (0.21 +/- 0.78). The positive predictive value of a low baseline ADAMTS5 level for predicting good response and remission (DAS28 < 2.6 at 38 weeks) was 90.0% and 70.0%, respectively. CONCLUSION: The baseline ADAMTS5 mRNA level is a candidate biomarker for prediction of the response to IFX in patients with RA.
20480201 Clinical evaluation of tocilizumab for patients with active rheumatoid arthritis refractor 2010 Aug We retrospectively observed the clinical efficacy and safety of tocilizumab (TCZ) in 74 patients with rheumatoid arthritis (RA) at 13 hospitals, without any restrictions on disease duration or stage, treatment history, and other influencing factors. TCZ was infused by the approved method, and disease activity was evaluated every 4 weeks until week 24 using a joint disease activity score (DAS28). Remission and treatment response were categorised using European League Against Rheumatism (EULAR) definitions. We also analysed the impact of previous treatment with other biologics and of concomitant methotrexate (MTX) therapy on the efficacy of TCZ. At week 24, the DAS28 had improved from 5.5 to 2.7 and the EULAR remission rate was 55.2%. Good and moderate responses according to the EULAR criteria were obtained in 61 and 36% of the patients, respectively. The biologic-naïve group had a significantly better DAS28 (2.1 vs. 2.8) and a significantly higher "good" response rate (86% vs. 54%) than the biologic-exposed group. Although the TCZ + MTX treatment group and the TCZ monotherapy group had a good response rate of 71 and 48%, respectively, the difference was not significant. Based on these results, we conclude that TCZ is able to significantly alleviate disease symptoms in a wide range of patients with RA in a normal clinical context.
19357794 Development and evaluation of a time-specific pulsatile-release tablet of aceclofenac: a s 2009 Jan The objective of this study was to develop and evaluate an oral chronomodulated drug delivery system (CDDS) for the treatment of rheumatoid arthritis with a distinct predetermined lag time of 6 h (+/- 0.25 h). The basic design of the system consisted of an inner core, an intermediate swelling layer and an external acid-resistant enteric layer applied by pan coating. Croscarmellose sodium was used as a disintegrant and swelling agent to create the desired rupturing pressure. A mixture of hydroxypropyl cellulose M (175 mg) and ethyl cellulose (25 mg) was used as an intermediate swelling layer. The lag time for the system was found to be independent of the effect of various parameters such as compression load, paddle rotation speed and pH of dissolution medium. For the enteric coating of the press-coated tablet an aqueous dispersion of Eudragit L30 D55 containing 15% of total solid content plasticized with 20 triethyl citrate was applied by conventional pan coater. An in vitro dissolution study of the prepared tablet was conducted initially for 2 h in simulated gastric fluid, and after that medium was changed to simulated intestinal fluid pH 6.8. A pharmacokinetic study was also used to establish in vitro methodology capable of predicting the subsequent in vivo performance of the time-dependent pulsatile-release system. Various pharmacokinetic parameters studied in rabbits as the animal model demonstrated that drug absorption was not influenced by the in vivo behavior of the pulsatile system. As per guidelines provided by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use and the World Health Organization, the formulation was found to be stable.
19308651 Association of the -1082 G/A promoter polymorphism of interleukin-10 gene with the autoant 2009 Aug Interleukin-10 (IL-10) is an immunoregulatory cytokine, usually considered to mediate the downregulation of the inflammatory response in rheumatoid arthritis (RA). Some effects of IL-10 are not anti-inflammatory; for example, the activation of B cells to promote autoantibody production. Allelic polymorphisms located in the promoter region of the IL-10 gene may contribute to the regulation of autoantibodies production. To examine the putative association between the -1082 G/A polymorphism in the promoter region of the IL-10 gene and the susceptibility to disease onset and severity of RA, a total of 144 patients with RA diagnosed according to the revised criteria of the American College of Rheumatology for RA were consecutively recruited into the study. Radiographic progression of RA was scored according to the Sharp/van der Heijde method. Serum levels of rheumatoid factors (RFs) were measured by enzyme-linked immunosorbent assay. Polymerase chain reaction amplification was used for the analysis of the promoter polymorphism of the IL-10 gene. We observed significant differences in genotype distribution of the -1082 G/A polymorphism between IgM RF, IgA RF, and IgG RF positive/negative subgroups of RA patients, with higher prevalence of the GG genotype within IgM RF (Pg = 0.006), IgA RF (Pg = 0.05), and IgG RF (Pg = 0.007) negative RA patients. Results obtained in this study provide the evidence of an association between the -1082 G/A polymorphism in the IL-10 gene promoter and the production of RFs in RA patients.
19849865 Determining a low disease activity threshold for decision to maintain disease-modifying an 2009 INTRODUCTION: The aim of this study was to determine a low disease activity threshold--a 28-joint disease activity score (DAS28) value--for the decision to maintain unchanged disease-modifying antirheumatic drug (DMARD) treatment in rheumatoid arthritis patients, based on expert opinion. METHODS: Nine hundred and sixty-seven case scenarios with various levels for each component of the DAS28 (resulting in a disease activity score between 2 and 3.2) were presented to 44 panelists. For each scenario, panelists had to decide whether or not DMARD treatment (excluding steroids) could be maintained unchanged. In each scenario, for decision, the participants were given the DAS28 parameters, without knowledge of the resultant DAS28. The relationship between panelists' decision, DAS28 value, and components of the score were analysed by multiple logistic regression analysis. Each panelist analysed 160 randomised scenarios. Intra-rater and inter-rater reproducibility were assessed. RESULTS: Forty-four panelists participated in the study. Inter-panelist agreement was good (kappa = 0.63; 95% confidence interval = 0.61 to 0.65). Intra-panelist agreement was excellent (kappa = 0.87; 95% confidence interval = 0.82 to 0.92). Quasi-perfect agreement was observed for DAS28 < or = 2.4, less pronounced between 2.5 and 2.9, and almost no agreement for DAS28 > 3.0. For values below 2.5, panelists agreed to maintain unchanged DMARDs; for values above 2.5, discrepancies occurred more frequently as the DAS28 value increased. Multivariate analysis confirmed the relationship between panelist's decision, DAS28 value and components of the DAS28. Between DAS28 of 2.4 and 3.2, a major determinant for panelists' decision was swollen joint count. Female and public practice physicians decided more often to maintain treatment unchanged. CONCLUSIONS: As a conclusion, panelists suggested that in clinical practice there is no need to change DMARD treatment in rheumatoid arthritis patients with DAS28 < or = 2.4.
20201075 META060 inhibits osteoclastogenesis and matrix metalloproteinases in vitro and reduces bon 2010 Jun OBJECTIVE: The multikinase inhibitor META060 has been shown to inhibit NF-kappaB activation and expression of markers of inflammation. This study was undertaken to investigate the effect of META060 on biomarkers associated with bone and cartilage degradation in vitro and its antiinflammatory efficacy in vivo in both acute and chronic inflammation models. METHODS: Glycogen synthase kinase 3beta (GSK3beta)-dependent beta-catenin phosphorylation was evaluated in RAW 264.7 macrophages to assess kinase inhibition. The inhibition of osteoclastogenesis and tartrate-resistant acid phosphatase (TRAP) activity was evaluated in RANKL-treated RAW 264.7 cells. The inhibition of interleukin-1beta (IL-1beta)-mediated markers of inflammation was analyzed in human rheumatoid arthritis synovial fibroblasts (RASFs). Mice with carrageenan-induced acute inflammation and collagen-induced arthritis (CIA) were used to assess efficacy. RESULTS: META060 inhibited the activity of kinases (spleen tyrosine kinase [Syk], Bruton's tyrosine kinase [Btk], phosphatidylinositol 3-kinase [PI 3-kinase], and GSK3) associated with RA and inhibited beta-catenin phosphorylation. META060 inhibited osteoclastogenesis, as indicated by decreased transformation of RAW 264.7 cells to osteoclasts and reduced TRAP activity, and inhibited IL-1beta-activated prostaglandin E(2), matrix metalloproteinase 3, IL-6, IL-8, and monocyte chemotactic protein 1 in RASFs. In mice with acute inflammation, oral administration of META060 reduced paw swelling similar to the effect of aspirin. In mice with CIA, META060 significantly reduced the arthritis index and decreased bone, joint, and cartilage degradation. Serum IL-6 concentrations in these mice were inhibited in a dose-dependent manner. CONCLUSION: Our findings indicate that META060 reduces swelling in a model of acute inflammation and inhibits bone and cartilage destruction in a model of chronic inflammation. Its efficacy is associated with the inhibition of multiple protein kinases, including Syk, Btk, PI 3-kinase, and GSK3. These results warrant further clinical testing of META060 for its therapeutic potential in the treatment of inflammatory diseases.
20697895 Resveratrol induces apoptosis MH7A human rheumatoid arthritis synovial cells in a sirtuin 2012 Jan Resveratrol, a phytoalexin, reduced the viability of MH7A cells, a human rheumatoid arthritis synovial cell line. In the apoptosis assay, resveratrol increased TUNEL-positive cells and stimulated H2A.X phosphorylation. Resveratrol disrupted mitochondrial membrane potentials in MH7A cells and stimulated cytochrome c release from the mitochondria to the cytosol. Resveratrol activated caspase-3 and caspase-9 but not caspase-8 in MH7A cells. Resveratrol upregulated the expression of the NAD-dependent deacetylase sirtuin 1 mRNA and downregulated the expression of the Bcl-X(L) mRNA, and resveratrol-induced MH7A cell death, mitochondrial damage, and caspase-3/-9 activation were prevented by sirtinol, an inhibitor of sirtuin 1. The results of the present study show that resveratrol induces MH7A cell apoptosis by activating caspase-9 and the effector caspase-3 along mitochondrial disruption as a result of reduced Bcl-X(L) expression, allowing cytochrome c release from the mitochondria into the cytosol, in a sirtuin 1-dependent manner. This suggests that resveratrol could suppress hyperplasia of synovial cells, a critical factor of rheumatoid arthritis.
20083537 How to improve DAS28 use in daily clinical practice?--a pilot study of a nurse-led interve 2010 Apr OBJECTIVES: To determine whether DAS28 measurements by a specialized nurse, before the rheumatologist visit, in combination with the advice to rheumatologists to reach a DAS28 < or = 3.2, had beneficial effects on disease activity and medication prescription in patients with RA and to explore possible predictors for variation in medication changes and reasons for non-adherence to the advice to reach a DAS28 < or = 3.2. METHODS: In this pilot study, rheumatologists were randomized to 'usual care' (n = 3) or DAS28 measurement by a nurse prior the rheumatologist visit (n = 4). In the usual care group, the DAS28 was measured but not provided to rheumatologists. Mixed model analyses were used for analysing between-group differences and for the prediction model. Rheumatologists in the intervention group were asked to provide reasons in cases of non-adherence to the advice. RESULTS: After 18 months, DAS28 was reduced by - 0.69 and - 0.66 (P = 0.70) in, respectively, the intervention (144 patients) and the usual care (104 patients) groups. In the intervention group, medication was changed by rheumatologists in 35% of the visits with a DAS28 > 3.2; in the usual care group this was 33% (P = 0.99). Baseline DAS28 (OR 1.6; P< or =0.0001) and HAQ (OR 1.3; P = 0.03) were positively related to a medication change. The most frequently mentioned reason not to change medication was patient refusal (26%). CONCLUSIONS: DAS28 measurement by a nurse was as effective as usual care; however, this intervention without protocolized treatment adjustments is not sufficient to lead to a considerable reduction in disease activity compared with trials with protocolized treatment adjustments.
19264727 Valuing health: does enriching a scenario lead to higher utilities? 2009 May OBJECTIVES: Patients have been found to value their own experienced health state higher than an investigator-constructed scenario of that health state. The aim of this study was to investigate if patients value their own experienced health state higher than a standard EQ-5D scenario of their health state and if "enriching'' this scenario by adding individualized attributes reduces the differences between experienced health and the scenario. METHODS: Face-to-face interviews were held with 129 patients with rheumatoid arthritis. Patients were asked to value in a time tradeoff their own experienced health; 6 standard EQ-5D scenarios, of which the 5th (untold to them) represented their own health state; and a standard EQ-5D scenario of their health state (identified as such) enriched with individual attributes. RESULTS: The own experienced health state was not valued differently from the own standard EQ-5D state and was lower compared to the own enriched EQ-5D state of that same health state. An interaction effect was found for health status. Patients with better health did not report different values for their own experienced health compared with their own standard EQ-5D description; their own experienced state was rated lower than their own enriched EQ-5D description. Patients with poor health valued all 3 health states similarly. Surprisingly, utilities for scenarios enriched with exclusively negative individual attributes were not lower than those for the own standard EQ-5D description. CONCLUSION: The hypothesis that disparities in valuation can be attributed to EQ-5D description being too sparse was not confirmed.
19597294 Expression of ICAM1 and VCAM1 serum levels in rheumatoid arthritis clinical activity. Asso 2009 To investigate the association of sICAM-1 and sVCAM-1 with ICAM1 721G>A and VCAM1 1238G>C polymorphisms and rheumatoid arthritis (RA) clinical activity, sixty RA patients and 60 healthy non-related subjects (HS) matched for age and sex were recruited. Soluble adhesion molecules were determined by ELISA technique. Rheumatoid factor (RF), C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured by routine methods. Disability and clinical activity was measured with Spanish-HAQ-DI and DAS28 scores, respectively. The ICAM1 and VCAM1 polymorphism were identified using the PCR-RFLP procedure. Inter-group comparison showed increased levels of sICAM-1 and sVCAM-1 in RA patients (284 and 481 ng/mL) versus HS (132 and 280 ng/mL); in the RA group, significant correlations between sVCAM-1 and RF (r = 0.402), ESR (r = 0.426), Spanish-HAQ-DI (r = 0.276), and DAS28 (r = 0.342) were found, whereas sICAM-1 only correlated with RF (r = 0.445). In RA patients, a significant association with the 721A allele of ICAM1 polymorphism (p = 0.04), was found. In addition, the allele impact (G/A+A/A) of this polymorphism was confirmed, (p = 0.038, OR = 2.3, C.I. 1.1-5.0). sVCAM-1 and sICAM-1 serum levels reflected the clinical status in RA, independently of the ICAM1 and VCAM1 polymorphism. However, the ICAM1 721A allele could be a genetic marker to RA susceptibility.
18762862 Response of early active rheumatoid arthritis to tumor necrosis factor inhibitors: evaluat 2009 Inflammatory changes (synovitis and bone marrow edema) and destructive changes (bone erosion) were evaluated by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA), and their relations with disease activity were assessed during treatment with tumor necrosis factor (TNF) inhibitors. Ten patients with early active RA underwent MRI at 0 and 16 weeks of TNF-inhibitor treatment. The carpal bones of the dominant hand were evaluated by the outcome measures in rheumatology clinical trials MRI score for RA. After 16 weeks, the mean disease activity score (DAS 28) decreased significantly from 5.54 to 2.70, while the number of tender joints, number of swollen joints, and inflammatory parameters were also significantly improved. The mean synovitis and marrow edema scores determined by MRI showed a significant decrease from 6.1 to 2.2 and 12.8 to 6.2, respectively, while the annual bone-erosion progression score decreased from 12.6 to 2.0. Although synovitis persisted in some patients, imaging remission was achieved in two patients. In conclusion, TNF-inhibitor therapy achieved an early decrease of disease activity and MRI revealed amelioration of joint destruction. The MRI score for RA is useful for assessing the early response to TNF inhibitors.
20659309 'I start my day by thinking about what we're going to have for dinner'--a qualitative stud 2011 Jun The aim of this study was to address the question of how older men with somatic diseases living in their own home approach the question of food-related activities (FRA). Further, any adaptations of these activities necessitated by effects of diseases and of altered life circumstances were explored. Interviews were conducted with a purposeful sample of 18 co-living and single-living men, 64-84 years old. They were diagnosed with Parkinson's disease, rheumatoid arthritis or stroke. In the analysis, a thematic framework was used. The findings revealed three food-related approaches, namely 'Cooking as a pleasure', describing joy in cooking; 'Cooking as a need', indicating no habits or skills in cooking; and 'Food is served', that is, being served meals by a partner. It was found that gender-related roles in particular, but also changed life circumstances, activity limitations, personal interests, and a wish to maintain continuity and independence, affected the men's approaches to these activities. This knowledge may be useful in attempts to facilitate and support FRA among elderly men with diseases. Health care efforts to promote FRA should preferably be individualised in respect to older men's approaches to these activities.
21031285 Comprehensive rehabilitation of patients with rheumatic diseases in a warm climate: a lite 2010 Nov OBJECTIVE: To present the evidence for the efficacy of comprehensive rehabilitation in a warm climate of patients with a wide variety of rheumatic diseases. METHODS: A systematic review of the literature was undertaken, searching in PubMed, Cinahl, Pedro, SweMed and Embase from 1970 to 2010, and using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation system) criteria. RESULTS: Six studies met the inclusion criteria. For patients with rheumatoid arthritis, moderate evidence was found for reduction of disease activity, pain, fatigue, and global disease impact. The evidence was also moderate that comprehensive rehabilitation in a warm climate did not improve fitness or reduce activity limitation beyond levels reached by rehabilitation in Scandinavia. Among patients with ankylosing spondylitis, low evidence was found for reduction of disease activity, pain, joint range of motion, activity limitation, and global disease impact. In groups with mixed rheumatic diagnoses, low evidence was found for reduction of pain, activity limitation, global disease impact and improved health-related quality of life. No studies on psoriatic arthritis, osteoarthritis, fibromyalgia or osteoporosis were found. CONCLUSION: Well-designed studies to validate and improve the low-to-moderate evidence found for the efficacy of comprehensive rehabilitation in a warm climate among patients with inflammatory rheumatic disease are greatly needed.
20542894 Persistently moderate DAS-28 is not benign: loss of function occurs in early RA despite st 2010 Oct OBJECTIVES: Current UK management of RA initially employs conventional DMARDs, with biological therapy reserved for DMARD-resistant RA patients with persistently high 28-joint disease activity score (DAS-28). The aim of this study was to examine the effect on patient-reported function of persistently moderate DAS-28 despite modern step-up DMARD therapy in an early arthritis cohort. METHODS: Data were obtained from the Yorkshire Early Arthritis Register, a cohort of early (<12 months) RA patients treated with dose-escalated DMARDs. Change in HAQ exceeding the minimum clinically important difference (MCID) was determined for three values of MCID (0.22, 0.31 and 0.49). Changes in HAQ over Months 6-12 were compared between patients whose DAS-28(ESR) was persistently high (> 5.1 at 6- and/or 9-month visits and at the 12-month visit), persistently moderate (>3.2 and ≤ 5.1) or persistently low (≤ 3.2). RESULTS: We selected 194 patients for this analysis. Deteriorating HAQ scores were observed in 10.9% of patients with persistently low DAS-28 compared with 21.4% (persistently moderate DAS-28) and 46.7% (persistently high DAS-28), respectively, for MCID = 0.22; 7.3, 14.3 and 20.0% for MCID = 0.31; 5.5, 10.7 and 11.1% for MCID = 0.49. CONCLUSIONS: A high DAS-28 was generally associated with a greater degree of functional decline, but persistent moderate elevation of DAS-28 was associated with important functional deterioration in 10-21% of early RA patients (depending on choice of MCID) following a modern DMARD protocol. A proportion of patients with persistently moderate DAS-28 may therefore benefit from more aggressive therapy than that allowed by current UK recommendations.
20187135 Two-year clinical and radiographic results with combination etanercept-methotrexate therap 2010 Mar OBJECTIVE: To evaluate how continuation of and alterations to initial year 1 combination etanercept-methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and radiographic progression in early, active rheumatoid arthritis. METHODS: Subjects were randomized at baseline for the entire 2-year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n = 111) or received etanercept monotherapy (the EM/E group; n = 111) in year 2; the original MTX monotherapy group either received combination therapy (the M/EM group; n = 90) or continued monotherapy (the M/M group; n = 99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28] <2.6) and radiographic nonprogression (change in the modified Sharp/van der Heijde score < or = 0.5) at year 2. A last observation carried forward analysis from the modified intention-to-treat population (n = 398) and a post hoc nonresponder imputation (NRI) analysis (n = 528) were performed for remission. RESULTS: At year 2, DAS28 remission was achieved by 62/108, 54/108, 51/88, and 33/94 subjects in the EM/EM, EM/E, M/EM, and M/M groups, respectively (P < 0.01 for the EM/EM and M/EM groups versus the M/M group). This effect was corroborated by a more conservative post hoc 2-year NRI analysis, with remission observed in 59/131, 50/134, 48/133, and 29/130 of the same respective groups (P < 0.05 for each of the EM/EM, EM/E, and M/EM groups versus the M/M group). The proportions of subjects achieving radiographic nonprogression (n = 360) were 89/99, 74/99, 59/79, and 56/83 in the EM/EM (P < 0.01 versus each of the other groups), EM/E, M/EM, and M/M groups, respectively. No new safety signals or between-group differences in serious adverse events were seen. CONCLUSION: Early sustained combination etanercept-MTX therapy was consistently superior to MTX monotherapy. Combination therapy resulted in important clinical and radiographic benefits over 2 study years, without significant additional safety risk.
20082104 Assessment of the effectiveness of low-level laser therapy on the hands of patients with r 2010 May Assess the effectiveness of low-level laser therapy on pain reduction and improvement in function in the hands of patients with rheumatoid arthritis. A randomized double-blind controlled trial was carried out on 82 patients with rheumatoid arthritis. The experimental group was submitted to the application of laser therapy, whereas the control group received a placebo laser. Aluminum gallium arsenide laser was used, at a wavelength of 785 nm, dose of 3 J/cm(2) and mean power of 70 mW. The groups were homogenous at the beginning of the study with regard to the main variables (p > 0.05). There were no statistically significant differences between groups in most of the measurements taken at the end of the intervention including the primary variables; the following variables were the exceptions: favoring the experimental group-inflammation of the interphalangeal joint of the right thumb (p = 0.012) and perimetry of the interphalangeal joint of the left thumb (p = 0.013); and favoring the control group-flexion of the proximal interphalangeal joint of the right fifth finger (p = 0.021), perimetry of the third proximal interphalangeal joint of the right hand (p = 0.044), grip strength in the left hand (p = 0.010), and the work domain of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire (p = 0.010). We conclude that low-level aluminum gallium arsenide laser therapy is not effective at the wavelength, dosage, and power studied for the treatment of hands among patients with rheumatoid arthritis.
20942734 Knee cartilage quality assessed with dGEMRIC in rheumatoid arthritis patients before and a 2010 Nov BACKGROUND: TNF-α inhibitors are potent anti-inflammatory drugs that have revolutionized the treatment of rheumatoid arthritis (RA). Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a non-invasive method to study cartilage quality, in particular the glycosaminoglycan (GAG) content. PURPOSE: To evaluate knee cartilage quality before and after treatment with a TNF-α inhibitor (infliximab) in patients with RA using dGEMRIC and to study clinical parameters and serum cartilage oligomeric protein (COMP) after the same treatment. MATERIAL AND METHODS: Seven patients with chronic RA received infusions of 3 mg/kg infliximab at weeks 0, 2, 6, 14, and 22. Clinical examination, serum COMP level, and dGEMRIC scans (1.5 T) were performed at baseline and after 7 months. The dGEMRIC index (ms), reflecting cartilage GAG content, was calculated using an inversion recovery sequence in the femoral weight-bearing cartilage. Seven years after treatment, charts were reviewed regarding joint replacement surgery (TKA). RESULTS: Clinical parameters showed an improvement for all patients after the 7-month treatment period. Serum COMP decreased from 13±4.5 to 11±3.4 (μg, mean ± SD) μg/ml (P<0.05). The dGEMRIC index was lower at follow-up than at baseline, 332±85 and 382±69 (ms, mean ± SD), respectively (P<0.05), indicating loss of GAG. The two patients with the lowest dGEMRIC index had received a TKA 7 years after treatment. CONCLUSION: This longitudinal study indicates a substantial GAG loss from the knee cartilage matrix in patients with chronic RA. Treatment with infliximab does not seem to protect the cartilage from further deterioration despite improvements in clinical parameters and decreased serum COMP.
20536600 Incidence of gastroduodenal ulcers during treatment with celecoxib or diclofenac: pooled r 2010 May AIM: To test whether treatment with celecoxib reduces the incidence of gastroduodenal ulcers compared to diclofenac in Asian patients with osteoarthritis (OA) or rheumatoid arthritis (RA) with minimal significant risk factors. METHODS: Patients with a clinical diagnosis of OA or RA of at least 3 months were randomized to 12 weeks of double-blind treatment with celecoxib 100 mg twice daily (n = 440) or diclofenac 50 mg twice daily (n = 440). The primary outcome was the gastric and/or duodenal ulcer rate at endpoint as determined by upper gastrointestinal endoscopy performed during the screening week, and at endpoint. RESULTS: There was no significant difference in the overall incidence of gastroduodenal ulcers at 12-week endpoint for celecoxib compared to diclofenac (2.8% vs. 5.1%; Cochran-Mantel-Haenszel [CMH] chi(2) P = 0.083). However, there was a significantly lower incidence of gastric ulcers on celecoxib versus diclofenac (0.5% vs. 3.6%; CMH chi(2) P = 0.002). Approximately 59% of patients in both treatment groups had no visible gastric lesions at endpoint; and a similar proportion were found to have one or more erosions on celecoxib (n = 85; 21.4%) and diclofenac (N = 91; 23.3%). A survival analysis of time to ulcer was significant for gastric ulcers (log-rank P = 0.004), but not for duodenal ulcers, or for gastroduodenal ulcers combined. Fewer patients reported at least one adverse event on celecoxib compared to diclofenac (42.4% vs. 50.3%; chi(2), 5.52; P = 0.019). CONCLUSIONS: In Asian patients with minimal significant risk factors, treatment with celecoxib was associated with a modest but significantly reduced incidence of gastric ulcers at the end of 12 weeks.
19811352 Lack of an association of GNB3 C825T polymorphism and blood pressure in patients with rheu 2009 Jul G-protein beta 3 subunit (GNB3) C825T (rs5443) single nucleotide polymorphism (SNP) has been implicated as a risk factor for essential hypertension in the general population. The effects of this SNP may be more prominent in subjects with endothelial dysfunction (ED). Rheumatoid arthritis (RA) is associated with ED and has a high prevalence of hypertension. Thus far, this SNP has not been studied in RA patients. We genotyped 383 RA patients and 432 controls. GNB3 C825T was identified using real-time polymerase chain reaction (PCR) and melting curve analysis. There were no differences in the frequencies of the GNB3 C825T genotype and alleles between RA and controls. Within RA patients, prevalence of hypertension did not differ across genotypes. The TT versus CC+CT contrast yielded an adjusted odds ratio (OR) of 0.92 (95% CI: 0.49 to 1.76, p = 0.813), the contrast of TT+CT versus CC an adjusted OR of 2.17 (95% CI: 0.885 to 5.30, p = 0.091), whereas that of the T allele versus C allele an adjusted OR of 1.11 (95% CI: 0.76 to 1.61, p = 0.604). Systolic and diastolic blood pressure levels were not significantly different across the three genotypic groups. No significant interaction was observed between GNB3 825C/T polymorphism and serum endothelin levels. Data from the present study suggest that the T825 variant of the G protein beta 3 subunit gene is unlikely to constitute major susceptibility loci for essential hypertension in Caucasian RA patients. Further larger studies are required to confirm our findings and assess the interaction of rs5443 with environmental factors.