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ID PMID Title PublicationDate abstract
21222644 The role of coagulation in chronic inflammatory disorders: a jack of all trades. 2011 Chronic inflammatory disorders constitute a heterogeneous group of complex and multifactorial diseases, which are often associated with increased cardiovascular morbidity and mortality, independent of the established cardiovascular risk factors. In keeping with this observation, hypercoagulability is frequently observed in patients suffering from atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis although the physiological significance of activated coagulation remained elusive. However, the identification of protease activated receptors (PAR) seem to provide a link between coagulation activation and disease progression as their activation by coagulation factors triggers a broad range of signaling pathways relevant for chronic inflammatory disorders. In experimental animal models, anticoagulation and/or genetic ablation of PAR signaling affords protection against the perpetuation of atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis. It is thus tempting to speculate that targeting the coagulation-PAR axis might have clinical relevance in the setting of chronic inflammatory disorders. In the current review, we discuss the current knowledge on coagulation activation in inflammatory disorders, we discuss the relationship between atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis and we review the current knowledge on PAR signaling in these disorders.
22042492 Primary biliary cirrhosis in a rheumatoid arthritis patient treated with rituximab, a case 2012 Feb Primary biliary cirrhosis (PBC) is an autoimmune disease in which intrahepatic bile ducts are targeted by an immune-mediated injury. This disease tends to progress to fibrosis and cirrhosis with hepatic failure. The authors report a case of a 50-year-old rheumatoid arthritis (RA) patient, with erosions and seropositive for rheumatoid factor and anti-citrullinated peptide antibodies, with 18 years disease duration refractory to prednisolone and several disease-modifying antirheumatic drugs, either conventional or biological (adalimumab and etanercept). In April 2007, she started therapy with rituximab (RTX) with good European League Against Rheumatism response achieved 9 months later. In June 2008, she was admitted with intrahepatic cholestasis, steatorrhea, and spontaneous fractures of various ribs. After excluding cholelitiasis, as well as infectious and neoplastic diseases a liver biopsy was performed that was compatible with the diagnosis of PBC. The antinuclear antibodies (1/160) were positive as well as the antimitochondrial antibodies (1/640). Other antibodies were negative such as anti-SSA and anti-SSB. Afterwards, the patient started ursodesoxycholic acid 15 mg kg(-1) day(-1) with progressive improvement of cholestatic markers. A labial salivary gland biopsy was performed and showed findings compatible with the concomitant diagnosis of Sjögren's syndrome. Based on this clinical report, a detailed review of the clinical aspects of PBC is presented as well as its association with other immune-mediated inflammatory diseases, particularly, with RA.
22251373 Identification and evaluation of novel synovial tissue biomarkers in rheumatoid arthritis 2012 Jan 17 INTRODUCTION: Suitable biomarkers are essential for therapeutic strategies in personalized medicine in terms of diagnosis as well as of prognosis. With highly specific biomarkers, it is possible, for example, to identify patients with poor prognosis, which enables early intervention and intensive treatment. The aim of this study was to identify and validate biomarkers and possible combinations for a prospective use in immunoscintigraphy, which may improve diagnosis of rheumatoid arthritis (RA) patients with consideration of inflammatory activity in the affected joints. Therefore, we tested several monoclonal antibodies (mAbs) directed against cellular-surface molecules on cells likely to be involved in the pathogenesis of RA. METHODS: Synovial tissue from patients with long-standing RA (accompanied by synovitis with varying states of current activity) and patients with acute non-RA arthritis were stained for surface molecules on different cell types by using fluorochrome-labeled antibodies. Tissue analysis was done by laser scanning cytometry (LSC), and statistical evaluation, by discriminant analysis and ROC analysis. RESULTS: CD11b, HLA-DR, CD90, and CD64 revealed significant differences between tissues from patients with RA and acute non-RA arthritis. Especially with the expression of CD64, both patient cohorts could be discriminated with high sensitivity and specificity. RA classification was improved by simultaneously investigating the expression of two or three different surface proteins, such as HLA-DR, CD90, and CD29 in the tissue. The simultaneous analysis of CD64 together with CD304 or the combination of CD11b and CD38 was suitable for the identification of RA patients with high current activity in synovitis. CONCLUSIONS: In this study, we showed that LSC is a novel reliable method in biomarker prevalidation in RA. Hence, identified mAbs in situ may allow their potential use in in vivo approaches. Moreover, we proved that biomarker-combination analysis resulted in better discrimination than did single-marker analysis. Combinations of these markers make a novel and reliable panel for the discrimination between RA and acute non-RA arthritis. In addition, further expedient combinations may be novel promising biomarker panels to identify current activity in synovitis in RA.
22155198 Estrogen metabolism and autoimmunity. 2012 May Epidemiological and experimental immunological evidence suggest that estrogens enhance the humoral immune response, and at the same time, seem to play important roles in pathophysiology of autoimmune rheumatic diseases. Estrogens in human subjects are generally considered as enhancers of cell proliferation (anti-apoptotic), however, rather than through their serum levels (that may exert opposite dose-related effects), they play important roles through their peripheral metabolites especially in autoimmune rheumatic diseases. Several investigations strongly support an accelerated aromatase-mediated peripheral metabolic conversion of upstream androgen precursors to estrogen metabolites in peripheral tissues affected by immune/inflammatory reactions, both, in male and female patients. In RA synovial tissue, biological effects of these metabolites as a consequence of altered peripheral sex hormone synthesis (intracrine, e.g., at the level of macrophages and fibroblasts) mainly results in stimulation of cell proliferation and cytokine production (i.e. TNF). It was shown that RA synovial cells mainly produce the cell proproliferative 16alpha-hydroxyestrone which, in addition to 16alpha-hydroxy-17beta-estradiol, is the downstream estrogen metabolite that interferes with monocyte proliferation. Therefore, a preponderance of 16alpha-hydroxylated estrogens is an unfavorable sign, at least, in synovial inflammation and possibly related synovial tissue hyperplasia. Interestingly, urinary concentration and total urinary loss of 2-hydroxyestrogens was found 10 times higher in healthy subjects compared to RA or SLE patients irrespective of prior prednisolone treatment or sex. The intracrine synthesis of active estrogen metabolites at the level of cells involved in the immune response (e.g. macrophages and fibroblasts) represents a common pathway that characterizes a similar final immune reactivity in both male and female patients.
21763468 Autoimmunity in 2010. 2011 Oct There is now growing evidence that autoimmunity is the common trait connecting multiple clinical phenotypes albeit differences in tissue specificity, pathogenetic mechanisms, and therapeutic approaches cannot be overlooked. Over the past years we witnessed a constant growth of the number of publications related to autoimmune diseases in peer-reviewed journals of the immunology area. Original data referred to factors from common injury pathways (i.e. T helper 17 cells, serum autoantibodies, or vitamin D) and specific diseases such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. As an example, the issue of a latitudinal gradient in the prevalence and incidence rates has been proposed for all autoimmune diseases and was recently coined as geoepidemiology to suggest new environmental triggers for tolerance breakdown. The present article is aimed at reviewing the articles that were published over the past year in the major autoimmunity and immunology journals.
22532509 Accuracy of pharmacy and coded-diagnosis information in identifying tuberculosis in patien 2012 Jun PURPOSE: Previous studies suggest that disease-modifying anti-rheumatic drugs (DMARDs) increase tuberculosis (TB) risk. The accuracy of pharmacy and coded-diagnosis information to identify persons with TB is unclear. METHODS: Within a cohort of rheumatoid arthritis (RA) patients (2000-2005) enrolled in Tennessee Medicaid, we identified those with potential TB using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) diagnosis codes and/or pharmacy claims. Using the Tennessee TB registry as the gold standard for identification of TB, we estimated the sensitivity, specificity, predictive values, and the respective 95% confidence intervals for each TB case-ascertainment strategy. RESULTS: Ten of 18,094 RA patients had confirmed TB during 61,461 person-years of follow-up (16.3 per 100,000 person-years). The sensitivity and positive predictive value (PPV) and respective 95% confidence intervals were low for confirmed TB based on ICD9-CM codes alone (60.0% (26.2-87.8) and 1.3% (0.5-2.9)), pharmacy data alone (20% (2.5-55.6) and 4.1% (0.5-14.3)), and both (20% (2.5-55.6) and 25.0% (3.2-65.1)). CONCLUSIONS: Algorithms that use administrative data alone to identify TB have a poor PPV that results in a high false positive rate of TB detection.
22521292 Sulfuretin, a major flavonoid isolated from Rhus verniciflua, ameliorates experimental art 2012 May 22 AIM: Sulfuretin, a major flavonoid isolated from Rhus verniciflua, is known to have anti-inflammatory effects. However, the mechanisms underlying the anti-inflammatory effect of sulfuretin on rheumatoid arthritis have not been elucidated. In this study we investigated whether sulfuretin treatment modulates the severity of arthritis in an experimental model. MAIN METHODS: We evaluated the effects of sulfuretin on tumor necrosis factor-α (TNF-α)-treated human rheumatoid fibroblast-like synoviocytes (FLS) in vitro and on collagen-induced arthritis (CIA) mice in vivo. KEY FINDINGS: In vitro experiments demonstrated that sulfuretin suppressed the chemokine production, matrix metalloproteinase secretion, and cell proliferation induced by tumor necrosis factor-α in rheumatoid FLS. In addition, sulfuretin inhibited the osteoclast differentiation induced by macrophage colony-stimulating factor and receptor activator of NF-κB ligand in bone marrow macrophages. In mice with CIA, early intervention with sulfuretin prevented joint destruction, as evidenced by a lower cumulative disease incidence and an absence of diverse disease features based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels. In mice with established arthritis, sulfuretin treatment significantly reduced synovial inflammation and joint destruction. The in vitro and in vivo protective effects of sulfuretin were mediated by inhibition of the NF-κB signaling pathway. SIGNIFICANCE: These results suggest that using sulfuretin to block the NF-κB pathway in rheumatoid joints reduces both inflammatory responses and joint destruction. Therefore, sulfuretin may have therapeutic value in preventing or delaying the progression of rheumatoid arthritis.
22253030 Total serum immunoglobulin levels in patients with RA after multiple B-cell depletion cycl 2012 May OBJECTIVE: To investigate whether the incidence of secondary hypogammaglobulinaemia in patients with RA following rituximab was related to patterns of B-cell return and relapse. METHODS: CD19(+) B-cell and serum immunoglobulin (sIg) determinations were done every 2 or 3 months in 137 consecutive patients treated with one or more courses of rituximab-based B-cell depletion therapy. The pattern of B-cell return, either concordant or discordant with relapse, was also recorded. RESULTS: There were 119 responders. Before treatment, three patients had low IgM and four had low IgG. After the first cycle, low IgM or IgG was present in 9.2% (11/119) and 11.8% (14/119) of the patients, respectively, increasing to 38.8% (8/18) and 22.2% (4/18) after five cycles. The mean percent maximum sIg decrease/cycle was relatively constant. The CD19(+) B-cell count at repopulation was not correlated with immunoglobulin (Ig) levels after each cycle. Patients discordant for B-cell return and relapse developed significantly lower serum IgM and more low IgM episodes than concordant patients (P < 0.05). CONCLUSION: Patients with lower baseline sIg levels tended to develop persistent IgM and IgG hypogammaglobulinaemia, resulting from an accumulation of incremental decreases after repeat cycles. This was not due to lower numbers of returning B cells in those developing low sIgs. The association of low IgM in patients with a discordant pattern of relapse suggests that underlying defects in B cells relating to survival and maturation into Ig-secreting cells, as well as attrition of IgG plasma cells may be contributing to low sIg levels in some patients.
21670670 Cardiovascular risk factors in inflammatory arthritis. 2011 Aug PURPOSE OF REVIEW: To assess factors that promote atherogenesis and cardiovascular disease (CVD) in rheumatoid arthritis (RA). Also, to determine how control of inflammation with conventional and biological antirheumatic drugs affects cardiovascular risk. RECENT FINDINGS: An excess risk of CVD occurs early in the RA disease course and indeed may predate disease onset. Inflammation is a key driver of CVD risk as it adversely affects body composition, glucose handling and lipid function, especially the atheroprotective role of high-density lipoprotein. Therapies for RA, especially hydroxychloroquine and methotrexate (MTX) have positive effects on cardiovascular risk factors such as glycaemic control and reverse cholesterol transport. MTX and antitumour necrosis factor-alpha drugs also appear to have beneficial effect on CVD event risk, although the data on MTX appears more consistently to favour such a benefit. SUMMARY: Future work needs to understand which aspects of the inflammatory state contribute most to CVD risk and whether specific anti-inflammatory agents, either alone or in combination, afford maximal CVD protection in RA.
22000818 Noninvasive cardiovascular imaging in rheumatoid arthritis: current modalities and the eme 2012 Apr OBJECTIVES: Rheumatoid arthritis (RA) is associated with premature atherosclerosis and increased prevalence of cardiovascular disease. The objective of this review is to summarize current and emerging imaging modalities for the evaluation of subclinical atherosclerosis in RA, with an emphasis on potential application of novel modalities, high-resolution magnetic resonance imaging and positron emission tomography, as screening tools for early cardiovascular disease risk stratification. METHODS: A PubMed literature search was undertaken using the search terms "rheumatoid arthritis" AND "cardiovascular disease" OR "atherosclerosis" OR "plaque" and including all relevant terms for imaging modalities. RESULTS: Two noninvasive imaging modalities have been widely adopted for direct visualization of arterial wall: carotid ultrasonography and cardiac computed tomography. Published studies in the RA population using these 2 modalities are reviewed. Novel cardiovascular imaging modalities are described, with an emphasis on high-resolution magnetic resonance imaging and positron emission tomography. Emerging research tools in vascular imaging, including dynamic and cardiac stress perfusion contrast-enhanced magnetic resonance imaging, are presented. The incremental imaging capabilities to characterize plaque composition and vessel wall inflammation as well myocardial abnormalities and published studies are systematically reviewed. CONCLUSIONS: An increasing number of cardiovascular imaging modalities with improved characterization of features associated with plaque vulnerability have been developed. Given the heightened cardiovascular risk profile of the RA population, these novel imaging modalities offer promise for risk stratification and drug safety evaluation.
20967860 The incidence of gastrointestinal perforations among rheumatoid arthritis patients. 2011 Feb OBJECTIVE: Gastrointestinal (GI) perforation has emerged as a novel safety concern in relation to medications used to treat rheumatoid arthritis (RA). This study was undertaken to characterize the incidence and risk factors for GI perforation in RA patients. METHODS: Using administrative databases of a large US health plan, we identified RA patients treated with biologic agents, methotrexate (MTX), oral glucocorticoids, and nonsteroidal antiinflammatory drugs (NSAIDs). Additional risk factors we evaluated included diverticulitis. Hospitalization with GI perforation was identified using a validated algorithm. Incidence rates and risk factors were evaluated using Cox proportional hazards models. RESULTS: Among 40,841 RA patients, 37 hospitalizations with GI perforation were identified. The rate of GI perforation among patients currently being treated with biologic agents who were also receiving oral glucocorticoids was higher (1.12 per 1,000 person-years [95% confidence interval (95% CI) 0.50-2.49]) than for patients being treated with biologic agents who were not also receiving glucocorticoids (0.47 per 1,000 person-years [95% CI 0.22-0.98]) or for patients being treated with MTX who were also receiving glucocorticoids (0.87 per 1,000 person-years [95% CI 0.36-2.10]). Neither biologic agents nor MTX was significantly associated with GI perforation, in contrast to current treatment with glucocorticoids and NSAIDs together (hazard ratio 4.7 [95% CI 1.9-12.0]) or glucocorticoids alone (hazard ratio 2.8 [95% CI 1.3-6.1]). Diverticulitis also was a strong risk factor (hazard ratio 9.1 [95% CI 3.1-26.4]). Seventy percent of patients with GI perforation received glucocorticoids, had antecedent diverticulitis, or both. CONCLUSION: GI perforation is an uncommon but serious adverse event among RA patients. Because a majority of patients with GI perforation were being treated with glucocorticoids or had previously experienced diverticulitis, these individuals should be considered at higher risk.
23102064 Connective tissue disease-associated lung disease. 2012 Nov This article provides a broad overview of the complex intersection between the connective tissue diseases (CTDs) and their pulmonary manifestations. Indirect pulmonary complications - such as respiratory infection and medication-induced lung toxicity - are briefly discussed, and the importance of a comprehensive assessment of the patient with CTD with respiratory symptoms is emphasized. A concise review of the many pulmonary manifestations of each specific CTD is provided, and particular emphasis is placed on CTD-associated interstitial lung disease.
21794790 [Descriptive study of the use of DMARD in patients with rheumatoid arthritis or persistent 2011 Mar INTRODUCTION: Rheumatoid arthritis is clinically very heterogeneous and variable in its progression, and no one treatment works the same for all patients, as this will depend on the clinical course and specific situations. OBJECTIVE: To describe the treatment with DMARDs established for the first time in patients with rheumatoid arthritis (RA) or persistent arthritis (PA) in routine clinical practice in Spain. MATERIAL AND METHODS: Epidemiological, cross-sectional, uncontrolled, multicenter study in 15 regions of Spain during a period of five months (July to November 2006). We included patients of both genders, aged 18 years and diagnosed with RA according to ACR criteria or PA defined as any arthritis (oligoarthritis or polyarthritis) lasting ≥12 weeks, which would be given DMARD to treat their disease. RESULTS: 1079 patients were recruited, 915 analyzed (33% ♂/♀ 67%) meeting all the criteria required to be evaluated in the study. Mean age of patients was 54.6 (SD=15.4) years. The mean time from onset of symptoms until the 1st visit with the rheumatologist was 6.3 (11.3) months and the time from the 1st visit with the rheumatologist and the start of treatment was 4 (13.5) months. Of the patients tested, 96.7% was treated with at least one DMARD, 62.1% were given NSAIDs, corticosteroids to 59.2% and 3.8% biological therapy. In patients who received DMARDs, 90.3% received treatment with a single DMARD, 9.5% with 2 DMARDs and 0.2% with three DMARDs. In polytherapy, the DMARDs that are most often administered together were MTX + hydroxychloroquine (4.8%), MTX + leflunomide (2.0%) and MTX + sulfasalazine (1.5%). The most frequently used DMARD in monotherapy was MTX (81.3%), followed by leflunomide (4.1%) and hydroxychloroquine (3.2%). In 89.6%, the treatment of first choice was adequate according to the SER. CONCLUSION: The most common pattern of initial treatment of RA is MTX monotherapy. Treatment of RA by rheumatologists has been homogenized in recent years.
21859702 The Sheffield rheumatoid arthritis health economic model. 2011 Sep The Sheffield RA health economic model has been used in several published cost-effectiveness analyses in both the UK and internationally to evaluate different treatments for patients with RA. This article presents the key methods and assumptions that underpin the model, including justifications for using an individual patient sampling methodology, and why the model has used the HAQ to track disease activity. The article also details how trial and observational data are used in the model to address specific questions. The model has been used to support health policy in both the UK and internationally, although the limited evidence still provides a challenge when using an economic model to determine the cost-effectiveness of RA treatments. The results of analyses using the Sheffield RA model are presented. The limitations of the model are discussed, and improvements are continually required to provide a model that is appropriate to address health economic questions in the future. The Sheffield RA model continues to be used and refined, and allows health economic questions to be answered using a transparent and flexible modelling methodology.
21774066 'I have come here to learn how to cope with my illness, not to be cured': a qualitative st 2011 Dec BACKGROUND: Self-management programmes (SMPs) have been developed to help patients with chronic rheumatic diseases to manage their health problems. Patients' expectations prior to treatment are important determinants of outcomes, and should therefore be identified, to ensure that interventions meet the participants' needs. The aim of the present study was to determine participant expectations with respect to a one-week inpatient SMP for those with fibromyalgia (FM) and rheumatoid arthritis (RA). METHODS: A qualitative study consisting of semi-structured interviews was used to explore the expectations of eight participants with FM and eight with RA. The data were analysed using thematic analysis. RESULTS: The findings show that the participants expected the SMP to be a turning point towards a better future and to empower them to assume more responsibility for their own health and self-care. They also expected the SMP to facilitate acceptance, help them to gain new knowledge and be a forum in which to share their experience. Participants who were employed assumed that participation in the SMP would help to ensure that they would continue in their jobs. CONCLUSIONS: This qualitative study indicated that identifying expectations prior to an SMP provides important information which has implications for the programme's implementation. Additional themes, such as acceptance of the illness and management of work, should also be included in the programmes and they should focus more on sharing experience.
21279966 Evaluation of intra-pelvic screw position prior to revision total hip arthroplasty--a repo 2011 Jan Neurovascular injury during total hip revision arthroplasty is rare, but potentially catastrophic. We report two patients requiring revision total hip arthroplasty with intrapelvic screw tips located close to the iliac artery. The screw tips were separated from artery by a retroperitoneal exposure prior to revision surgery. Assessment of screw position by computed tomography (CT) is important prior to revision total hip arthroplasty.
22972032 Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for drug the 2012 Sep 12 INTRODUCTION: We aimed to investigate the sensitivity and reliability of two-dimensional ultrasonographic endpoints at the metacarpophalageal joints (MCPJs) and their potential to provide an early and objective indication of a therapeutic response to treatment intervention in rheumatoid arthritis (RA). METHODS: A randomized, double-blind, parallel-group, two-center, placebo-controlled trial investigated the effect on ultrasonographic measures of synovitis of repeat dose oral prednisone, 15 mg or 7.5 mg, each compared to placebo, in consecutive two-week studies; there were 18 subjects in a 1:1 ratio and 27 subjects in a 2:1 ratio, respectively. All subjects met the 1987 American College of Rheumatology criteria for the diagnosis of RA, were ≥18 years-old with RA disease duration ≥6 months, and had a Disease Activity Score 28 based on C-reactive protein (DAS28(CRP)) ≥3.2. Subjects underwent high-frequency (gray-scale) and power Doppler ultrasonography at Days 1 (baseline), 2, 8 and 15 in the dorsal transverse and longitudinal planes of all 10 MCPJs to obtain summated scores of quantitative and semi-quantitative measures of synovial thickness as well as vascularity. The primary endpoint was the summated score of power Doppler area measured quantitatively in all 10 MCPJs in the transverse plane at Day 15. Clinical efficacy was assessed at the same time points by DAS28(CRP). RESULTS: All randomized subjects completed the trial. The comparison between daily 15 mg prednisone and placebo at Day 15 yielded a statistically significant treatment effect (effect size = 1.17, P = 0.013) in change from baseline in the primary endpoint, but borderline for prednisone 7.5 mg daily versus placebo (effect size = 0.61, P = 0.071). A significant treatment effect for DAS28(CRP) was only observed at Day 15 in the prednisone 15 mg group (effect size = 0.95, P = 0.032). However, significant treatment effects at all time points for a variety of ultrasound (US) endpoints were detected with both prednisone doses; the largest observed effect size = 2.33. Combining US endpoints with DAS28(CRP) improved the registration of significant treatment effects. The parallel scan inter-reader reliability of summated 10 MCPJ scores were good to excellent (ICC values >0.61) for the majority of US measures. CONCLUSIONS: Ultrasonography of MCPJs is an early, reliable indicator of therapeutic response in RA with potential to reduce patient numbers and length of trials designed to give preliminary indications of efficacy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00746512.
21954144 Thresholds in disease activity for switching biologics in rheumatoid arthritis patients: e 2011 Dec OBJECTIVE: To examine the threshold in disease activity associated with switching biologic treatment regimens in rheumatoid arthritis (RA) patients in real-world clinical practice. METHODS: Using data from a prospective observational North American cohort of RA patients through December 30, 2009, patients who initiated a new anti-tumor necrosis factor α (anti-TNFα) agent with ≥6 months of followup were identified. Patients were classified as switchers or maintainers depending on whether they continued their anti-TNF treatment or switched (including discontinuation) within 12 months. Level of disease activity measured by the Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints (DAS28) at the time of the switch (corresponding followup visit for maintainers) was examined and random-effect multivariable logistic regression was used to adjust for covariates. RESULTS: Mean age and RA duration among 1,549 eligible patients were 56.1 and 9.6 years, respectively, 80% were women, 62% were initiating their first biologic, and 30% were initiating their second biologic. At the time of the switch, the median DAS28 and CDAI score were 3.1 and 8.4 among maintainers and 4.0 and 15.2 among switchers, respectively. Maintainers also experienced a greater amount of reduction in disease activity compared with switchers (CDAI: -7.7 versus -2.3, DAS28: -1.1 versus -0.3). The threshold to switch decreased over calendar time, with the greatest amount of reduction observed among patients with moderate disease activity. CONCLUSION: On average, physicians and patients were willing to continue biologic treatment for patients who were at or near low disease activity. The threshold to switch decreased over time, especially among partial responders.
21688627 [The region of orthopaedic surgery and rheumatology]. 2011 Jun NSAIDs can cause serious GI complications such as peptic ulcers, perforations and bleeds and this risk increases with age, concurrent use of other medications, and probably with the duration of therapy. The recommendation that in patients with increased GI risk, either a COX-2 selective agent or a non-selective NSAID with co-prescription of a PPI or misoprostol for gastroprotection should be considered is supported by evidence from a systematic review of RCTs. There was no evidence for similar gastroprotection with H2 receptor antagonists and treatment with misoprostol is associated with an increase risk of diarrhea. The GI protection that is associated with the use of COX-2 selective agents is largely lost when low-dose aspirin is administered concurrently for CV prophylaxis.
22990668 Activation of liver X receptors suppresses inflammatory gene expressions and transcription 2013 Jan OBJECTIVES: Liver X receptors (LXR) are nuclear receptors that play important roles in lipid metabolism and transport. LXR also suppress inflammatory responses in macrophages through a unique mechanism of transrepression. This study was performed to investigate whether the synthetic LXR agonist GW3965 can modulate the inflammatory status of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and to identify the mechanism for their effect. METHODS: RA FLS were treated with 0.1 and 1 μM of GW3965, a synthetic LXR agonist. The mRNA expressions of pro-inflammatory mediators were measured using quantitative real-time PCR. Apoptotic cell death of RA FLS was assessed using TUNEL assay and determination of caspase-3 activity by a colorimetric assay. The levels of transcriptional corepressors including NCoR and SMRT were determined using western blot analyses. RESULTS: Treatment of RA FLS with GW3965 induced dose-dependent reductions in mRNA expression of pro-inflammatory mediators (IL-1β, IL-6, MMP-9, CCL-2, CCL-7, and COX-2). However, treatment with GW3965 at the concentration selected for this study had no effect on apoptosis of RA FLS. Decreased productions of NCoR and SMRT by LPS stimulation was attenuated by GW3965 treatment. CONCLUSIONS: GW3965 treatment suppressed mRNA expressions of pro-inflammatory mediators from RA FLS and inhibited the clearance of transcriptional corepressors. These data suggest that LXR activation can be used as a therapeutic approach to reduce the synovial inflammation in RA.