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ID PMID Title PublicationDate abstract
20034912 [Analgesic and anti-inflammatory effects of Hanshibi tablet in mice and its effect on syno 2009 Dec OBJECTIVE: To evaluate the analgesic and anti-inflammatory effects of Hanshibi tablet in Kunming mice and the effect of the tablet in ameliorating synovial pathology in a rat model of rheumatoid arthritis (RA). METHODS: Stretching test, capillary permeability and ear swelling test of Kunming were performed to observe the analgesic and anti-inflammatory effects of Hanshibi tablet administered intragastrically at different doses. In a SD rat model of RA induced by heat-inactivated Mycobacterium tuberculolytic H37Ra (Mtb), the effect of the tablet on the symptoms and progression of arthritis was observed regularly, and the numbers of the peripheral white blood cells, platelets and lymphocytes and mononuclear cells were measured. HE staining was used to examine the pathology of the rat ankle, and flow cytometry performed to monitor the changes in the T lymphocyte subsets. RESULTS: Hanshibi tablet treatment reduced the writhing response frequency and prolonged the stretching latency of Kunming mice. The tablet also inhibited the acetic acid-induced increase in capillary permeability and ear swelling. In the rat model of RA, administration of the tablet resulted in reduced ratio of CD4(+)/CD8(+), and significantly ameliorated synovial pathology. CONCLUSION: Hanshibi tablet has obvious analgesic and anti-inflammatory effects and ameliorates the synovial pathology in the rat model of RA possibly by regulating CD4(+)/CD8(+) balance.
20521331 Validity and responsiveness of the Michigan Hand Questionnaire in patients with rheumatoid 2010 Nov OBJECTIVE: Millions of patients experience the disabling hand manifestations of rheumatoid arthritis (RA), yet few hand-specific instruments are validated in this population. Our objective was to assess the reliability, validity, and responsiveness of the Michigan Hand Questionnaire (MHQ) in patients with RA. METHODS: At enrollment and at 6 months, 128 RA patients with severe subluxation of the metacarpophalangeal joints completed the MHQ, a 37-item questionnaire with 6 domains: function, activities of daily living (ADL), pain, work, aesthetics, and satisfaction. Reliability was measured using Spearman's correlation coefficients between time periods. Internal consistency was measured using Cronbach's alpha. Construct validity was measured by correlating MHQ responses with the Arthritis Impact Measurement Scales 2 (AIMS2). Responsiveness was measured by calculating standardized response means (SRMs) between time periods. RESULTS: The MHQ demonstrated good test-retest reliability (r = 0.66, P < 0.001). Cronbach's alpha scores were high for ADL (α = 0.90), function (α = 0.87), aesthetics (α = 0.79), and satisfaction (α = 0.89), indicating redundancy. The MHQ correlated well with AIMS2 responses. Function (r = -0.63), ADL (r = -0.77), work (r = -0.64), pain (r = 0.59), and summary score (r = -0.74) were correlated with the physical domain. Affect was correlated with ADL (r = -0.47), work (r = -0.47), pain (r = 0.48), and summary score (r = -0.53). Responsiveness was excellent among arthroplasty patients in function (SRM 1.42), ADL (SRM 0.89), aesthetics (SRM 1.23), satisfaction (SRM 1.76), and summary score (SRM 1.61). CONCLUSION: The MHQ is easily administered, reliable, and valid to measure rheumatoid hand function, and can be used to measure outcomes in rheumatic hand disease.
19286850 The gap between practice and guidelines in the choice of first-line disease modifying anti 2009 May OBJECTIVE: To compare rheumatologists' prescription for first disease modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA) in real-life settings with 2 clinical practice guidelines (CPG), the French Society of Rheumatology/STPR 2004 and EULAR/ESCISIT 2007, and thus assess the gap between practices and guidelines. Method. ESPOIR was a French multicenter cohort study of 813 patients with early arthritis between 2002 and 2005. "Definite" and "probable" RA were defined according to ACR criteria and the level of diagnostic certainty. The objectives were to assess conformity between the observed first-line DMARD prescribed for those patients and the DMARD recommended in the guidelines; and to conduct a mail survey of patients' usual rheumatologists to investigate the reasons for their nonconformity with guidelines. RESULTS: In total 627 patients with definite or probable RA were identified. Conformity rates were 58% for STPR guidelines and 54% for EULAR guidelines. At 6 months, 83 (34%) patients with early RA did not receive any DMARD. Main determinants associated with conformity to guidelines were disease activity and presence of severity-predictive factors. The main reason leading to a discrepancy between guidelines and daily practice appeared to be diagnostic uncertainty, i.e., the difficulty to reliably assess RA diagnosis as early as the first visits to the rheumatologist. CONCLUSION: There is a substantial gap between CPG and rheumatologists' daily practice concerning the first DMARD to prescribe in early RA. This is explained mainly by diagnostic uncertainty. More attention should be paid in future guidelines to the diagnostic difficulties of early RA.
19252239 [Recent advances in the pathogenesis of rheumatoid arthritis]. 2009 Mar Rheumatoid arthritis is a chronic inflammatory polyarthritis and is thought to be an autoimmune, multifactorial and polygenic disease. Recent studies have uncovered many important players in the pathogenesis of rheumatoid arthritis. Immune cells, mesenchymal cells, and bone-associated cells are all involved in the pathogenesis and are closely related with each other. The genetic predisposition to rheumatoid arthritis is confirmed by many family studies and HLA association studies. Genome-wide disease association studies identified genetic risk foci, such as HLA-DRB1, PADI4, and PTPN22. In addition to the genetic contribution, environmental factors are increasingly recognized. Many studies revealed that smoking is a risk factor for rheumatoid arthritis. The role of B and T lymphocytes in the pathogenesis has been reevaluated by biological agents such as rituximab (anti-CD20 antibody) and abatacept (CTLA4-Ig) , respectively. T cells in rheumatoid arthritis have been shown to have the altered level of surface molecules such as CD28, cytokine pattern shift, and shortened telomere lengths. Moreover, telomere loss is recognized not only in lymphocytes but also in hematopoietic progenitor cells. This phenomenon and the presence of rheumatoid-specific anti-citrullinated protein antibodies are reported to be associated with HLA haplotypes.
20535795 Factors that influence rheumatologists' decisions to escalate care in rheumatoid arthritis 2010 Jun OBJECTIVE: In order to improve adherence to treatment guidelines and performance indicators advocating tight control of disease activity in rheumatoid arthritis (RA), it is important to gain insight into the factors influencing rheumatologists' decisions whether or not to escalate care. Our objective was to determine the influence of specific attributes relative to a validated measure of disease activity (the Disease Activity Score [DAS]) on rheumatologists' decisions to escalate care. METHODS: We used a computer-based choice-based conjoint analysis survey to determine the relative importance of 6 attributes on rheumatologists' decisions related to escalation of care in RA. We administered the survey in a convenience sample of rheumatologists attending the 2008 American College of Rheumatology Annual Scientific Meeting. Utilities were calculated using hierarchical Bayes modeling, and these results were used to calculate the relative importance of each attribute. RESULTS: Rheumatologists assigned the most importance to the DAS score (relative importance of 30.7%) in their decision to escalate care. The age of the patient (21.5%) and erosions (20.5%) were rated as equally important in this decision. The decision to escalate care was least influenced by change in symptoms reported by the patient (11.1%), current treatment (8.9%), and disease duration (7.4%). CONCLUSION: Our findings suggest that rheumatologists endorse the DAS as a means to guide decision making in RA. We also found that age and erosions are important influences on rheumatologists' decisions to escalate care in RA. Our results add to the literature supporting age bias in RA and suggest that further research is needed to determine how age affects quality of care in clinical practice.
19369458 Correlation of CX3CL1 and CX3CR1 levels with response to infliximab therapy in patients wi 2009 Jun OBJECTIVE: To examine the relation between serum chemokine levels and patient responsiveness to infliximab, and the influence of infliximab administration on serum chemokine levels. METHODS: Serum levels of the chemokines CX3CL1, CXCL8, CCL3, and CXCL10 were quantified prior to (at baseline) and after 30 weeks of treatment with infliximab in 20 patients using enzyme-linked immunosorbent assays. Disease status was assessed using the Disease Activity Score (DAS28). The response to infliximab was classified according to the European League Against Rheumatism (EULAR) response criteria. RESULTS: By 30 weeks, infliximab produced a significant overall reduction in DAS28 among the 20 patients with RA, although only 12 achieved a good to moderate response based on EULAR response criteria. A significant reduction in CX3CL1 was seen in the responsive group, although infliximab treatment had no significant effect on the serum levels of the other 3 chemokines. Comparison of patients with lower (<2000 pg/ml) and higher (>or=2000 pg/ml) basal CX3CL1 levels revealed that DAS28, erythrocyte sedimentation rate, C-reactive protein, and CX3CL1 levels were all significantly diminished by infliximab in RA patients with lower basal CX3CL1 levels, but not in those with higher basal levels. In addition, cell-surface expression of CX3CR1 protein in peripheral blood CD8+CD3+ T cells and mRNA expression of CX3CR1 in lymphocytes were both significantly downregulated after infliximab treatment in the responsive group. CONCLUSION: Our results suggest that the CX3CL1-CX3CR1 system in patients with active RA may be sensitive to anti-tumor necrosis factor-alpha therapy, and confirm that CX3CL1 plays a crucial role in the pathogenesis of RA.
20197777 Methotrexate--how does it really work? 2010 Mar Methotrexate remains a cornerstone in the treatment of rheumatoid arthritis and other rheumatic diseases. Folate antagonism is known to contribute to the antiproliferative effects that are important in the action of methotrexate against malignant diseases, but concomitant administration of folic or folinic acid does not diminish the anti-inflammatory potential of this agent, which suggests that other mechanisms of action might be operative. Although no single mechanism is sufficient to account for all the anti-inflammatory activities of methotrexate, the release of adenosine from cells has been demonstrated both in vitro and in vivo. Methotrexate might also confer anti-inflammatory properties through the inhibition of polyamines. The biological effects on inflammation associated with adenosine release have provided insight into how methotrexate exerts its effects against inflammatory diseases and at the same time causes some of its well-known adverse effects. These activities contribute to the complex and multifaceted mechanisms that make methotrexate efficacious in the treatment of inflammatory disorders.
20490517 [How closely does rheumatology treatment follow the guidelines?: ambition and reality]. 2010 Jun In 2005, the first evidence-based German guideline on the management of early rheumatoid arthritis (RA) was published. With data from the national database of the German Collaborative Arthritis Centres and other health care studies we evaluated to what extent current health care is in accordance with the guideline's recommendations.A total of 66% of all newly referred RA patients seen at the national database centers in 2008 achieved the goal of seeing a rheumatologist within 3 months of symptom onset, while 75% were seen within 6 months. Before referral, 25% of the patients had DMARD therapy and 19% glucocorticoids. Of the patients in rheumatological care, 90% received DMARDs. The availability of early arthritis clinics determines the promptness of access to a rheumatologist.After 6 years of rheumatological care, around 80% of patients continuously seen were still under treatment with a conventional or biological DMARD. The highest continuation rates were seen for methotrexate monotherapy. Biologic agents were given in 2008 to 20% of patients. Of those with "severe" or "very severe" disease, 42% received biologics and 21% DMARD combination therapy. Low-dose glucocorticoids are the standard of care; of patients in rheumatological care, 88% received dosages up to 7.5 mg/d and 74% of up to 5 mg/d.
19630919 Cell specific synovial expression of nicotinic alpha 7 acetylcholine receptor in rheumatoi 2009 Aug Neuroimmune interactions are known to influence several chronic inflammatory and rheumatic diseases, but the underlying mechanisms have been insufficiently elucidated. The cholinergic anti-inflammatory pathway is characterized by neural regulation of systemic inflammation, mediated by the vagus nerve and specific cholinergic stimulation of the nicotinic alpha-7 acetylcholine receptor (alpha7nAChR) on immune cells. Moreover, alpha7nAChR has been shown important for immune regulation also in the absence of nerves, but little is known about these mechanisms in chronic joint inflammation. The expression and localization of alpha7nAChR in synovial biopsies from patients with rheumatoid arthritis and psoriatic arthritis was investigated by immunohistochemistry using monoclonal antibody against alpha7nAChR. Surface staining of alpha7nAChR was observed in synovial tissue of all arthritis patients investigated and could also to a lesser extent be detected in the synovium of healthy individuals. alpha7nAChR positive cells were detected in mainly synovial lining cells and vessels. The alpha7nAChR positively stained cells were by double immunofluorescence identified as primarily macrophages and fibroblasts, with the majority of these cells expressing the receptor. These results indicate the importance of alpha7nAChR and cholinergic mechanisms in arthritis pathogenesis and implicate specific cholinergic modulation as a potential anti-inflammatory therapeutic strategy in joint inflammation.
19926660 Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein a 2010 Mar Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease, characterized by chronic, erosive polyarthritis and by the presence of various autoantibodies in serum and synovial fluid. Since rheumatoid factor (RF) was first described, a number of other autoantibodies have been discovered in RA patients. The autoantigens recognized by these autoantibodies include cartilage components, chaperones, enzymes, nuclear proteins and citrullinated proteins. However, the clinical significances and pathogenic roles of these antibodies are largely unknown except for RF and anticitrullinated protein antibodies (ACPAs), whose clinical usefulness has been acknowledged due to their acceptable sensitivities and specificities, and prognostic values. This review presents and discusses the current state of the art regarding RF and ACPA in RA.
19969325 The involvement of heat-shock proteins in the pathogenesis of autoimmune arthritis: a crit 2010 Oct OBJECTIVES: To review the literature on the role of heat-shock proteins (HSPs) in the pathogenesis of autoimmune arthritis in animal models and patients with rheumatoid arthritis (RA). METHODS: The published literature in Medline (PubMed), including our published work on the cell-mediated as well as humoral immune response to various HSPs, was reviewed. Studies in the preclinical animal models of arthritis as well as RA were examined critically and the data are presented. RESULTS: In experimental arthritis, disease induction by different arthritogenic stimuli, including an adjuvant, led to immune response to mycobacterial HSP65 (BHSP65). However, attempts to induce arthritis by a purified HSP have not met with success. There are several reports of a significant immune response to HSP65 in RA patients. However, the issue of cause and effect is difficult to address. Nevertheless, several studies in animal models and a couple of clinical trials in RA patients have shown the beneficial effect of HSPs against autoimmune arthritis. CONCLUSIONS: There is a clear association between immune response to HSPs, particularly HSP65, and the initiation and propagation of autoimmune arthritis in experimental models. The correlation is relatively less convincing in RA patients. In both cases, the ability of HSPs to modulate arthritis offers support, albeit an indirect one, for the involvement of these antigens in the disease process.
20943049 A study of Adenosine-Deaminase genetic polymorphism in rheumatoid arthritis. 2010 Jul Recent investigations suggest that Adenosine Deaminase (ADA) could play a role in susceptibility to rheumatoid arthritis (RA). The purpose of our study is to investigate the possible role of genetic variability of ADA in the susceptibility to RA. We studied three intragenic ADA polymorphisms, ADA1, ADA2 and ADA6, in a sample of 91 subjects with RA and in 246 healthy subjects from the same Caucasian population and compared genotype and pairwise haplotype distributions between cases and controls. No statistically significant differences between RA and controls are observed for ADA genotypes. A border line difference for ADA1-ADA2 haplotype distribution is observed due to a decreased proportion of ADA1 *2/ADA2 *2 haplotype in RA compared to controls. Our data indicate a border line effect of ADA gene polymorphism on susceptibility to RA that need to be confirmed in other clinical settings.
19277815 Cardiovascular disease is associated with extra-articular manifestations in patients with 2009 Jul The objective of this study was to examine the clinical and genetic variables associated with extra-articular rheumatoid arthritis (ExRA). This was a cross-sectional study in which 538 Northwestern Colombian patients with rheumatoid arthritis (RA) were included. Information about demographics and clinical characteristics including disease activity, inflammatory markers, co-morbidities, cardiovascular (CV) risk factors, history of familial autoimmunity and therapy was recorded. The presence of HLA "shared epitope" (SE) alleles and TNF gene polymorphism was assessed. A multivariate statistical analysis was performed. ExRA was found in 32% of the patients, of which nodulosis, Sjögren's syndrome, and lung involvement were registered in 21%, 9%, and 4% of patients, respectively. Patients with ExRA were older than patients without it and they presented longer disease duration as well. Thus, an association between disease duration and ExRA manifestations was also observed. Patients with ExRA presented significant higher titers of anti-CCP antibodies as compared to patients without ExRA. Hypertension and thrombosis were significantly associated with ExRA. Never having smoked constituted a protective factor against ExRA onset. Associations between ExRA and the presence of traditional CV risk factors were also found. Our results show that duration of RA, CV disease and high titers of anti-CCP antibodies are associated with ExRA in Colombian patients with RA, and highlight the importance of preventing smoking in those who are prone to develop autoimmune diseases including RA.
20602811 The use of glucocorticoids in rheumatoid arthritis--no 'rational' approach yet. 2010 The relationship between glucocorticoids and bone mineral density in rheumatoid arthritis is complex. Further study into the optimal dosing, timing and duration of glucocorticoid use in rheumatoid arthritis is necessary.
20495924 [Recommendations of the German rheumatology society on the use of tocilizumab in rheumatoi 2010 Jun The humanized anti-IL-6 receptor monoclonal antibody tocilizumab (TCZ) represents a new therapy approach for moderately severe to severe cases of rheumatoid arthritis (RA). The IL-6 concentration in the synovial fluid and peripheral circulation of patients with RA is elevated. TCZ recognises the IL-6 binding site of human IL-6R and blocks the IL-6 signaling pathway. TCZ is capable of correcting a multitude of pathological processes in RA, as has been shown in a number of studies. TCZ treatment should be combined with methotrexate. If the latter cannot be administered, TCZ can also be used as a monotherapy. The recommended dose is 8 mg/kg once every 4 weeks; the minimum dose per infusion is 480 mg. Close monitoring, in particular for infectious complications, is necessary. Clinical effects of TCZ are usually seen several weeks following initiation of therapy. If no significant clinical response is seen within 6 months, TCZ therapy should be ceased.
19684147 Developing a standardized definition for disease "flare" in rheumatoid arthritis (OMERACT 2009 Oct OBJECTIVE: Traditional outcome measures in randomized controlled trials (RCT) include well-established response criteria as well as ACR EULAR responses using Disease Activity Score 44 (DAS44)/DAS28 to assess improvement; however, a measure to assess worsening of disease has yet to be developed. This special interest group (SIG) was established to develop an evidence-based, consensus-driven standard definition of "flare" in rheumatoid arthritis (RA). METHODS: At OMERACT 8, the need for a standardized definition of RA flare was recognized; interested individuals developed a proposal to form a SIG. A literature review was performed to identify publications and abstracts with flare definitions applied in RA, JIA, and lupus RCT as well as concerning patient perspectives on disease worsening. A SIG was held at OMERACT 9 with breakout sessions for patients and investigators. RESULTS: The RA flare SIG was attended by about 120 participants, including 11 patients. Patients and investigators held separate breakout sessions to discuss various aspects of disease worsening. The following consensus was obtained at OMERACT 9: a working definition of flare should indicate worsening of disease activity (88%), persistence, and duration as critical elements (77%), and consideration of change or increase in therapy (74%). CONCLUSION: A working definition of RA flare was developed based on these votes: flare is any worsening of disease activity that would, if persistent, in most cases lead to initiation or change of therapy; and a flare represents a cluster of symptoms of sufficient duration and intensity to require initiation, change, or increase in therapy. Using this working definition, evaluation of candidate domains will be conducted via Delphi exercise and further informed by patient focus groups. Validation of candidate definitions in appropriate RCT will be required.
19101756 Therapeutic effect of anti-vascular endothelial growth factor receptor I antibody in the e 2009 Mar Synovial angiogenesis plays an important role in the inflammation in rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) is a key molecule in angiogenesis and binds to specific receptors, known as vascular endothelial growth factor receptor I (VEGF RI). In this study, we investigated the therapeutic efficacy of anti-VEGF RI antibody (Ab) on RA using a collagen-induced arthritis (CIA) mouse model. Twelve DBA/1 mice were divided into three groups. All mice except controls were injected with type II collagen. Mice in the anti-VEGF-RI-Ab-treated groups were injected on one posterior paw with 50 microg anti-VEGF RI Ab twice weekly for 3 weeks. Arthritis score and paw thickness were measured and histopathologic assessment of joint sections was performed by hematoxylin-eosin. The infiltration of CD45+ inflammatory cells and neovascularization were evaluated by immunohistochemical staining. Anti-VEGF RI Ab significantly attenuated the arthritis severity and histopathologic findings in the CIA mice model. The infiltration of CD45+ cells decreased in anti-VEGF-RI-Ab-treated joint tissues. Staining for CD31 revealed reduced synovial neovascularization after anti-VEGF RI Ab treatment. The data showing that in vivo administration of anti-VEGF RI Ab suppressed arthritis in established CIA mice suggest anti-VEGF RI Ab treatment may serve as a new therapeutic modality for RA.
19882340 Anti-cyclic citrullinated peptide antibodies as a discriminating marker between rheumatoid 2011 Jan Articular involvement is a frequent extrahepatic manifestation of hepatitis C virus (HCV) infection. The distinction between HCV-related polyarthropathy and true RA may be very difficult, especially with recent onset RA before articular damage and erosions develop. The objective of the study is to assess the diagnostic utility of anti-CCP antibodies and compare it with that of rheumatoid factor (RF) in distinguishing between rheumatoid arthritis (RA) and HCV-related polyarthropathy. Anti-cyclic citrullinated peptide (CCP) antibodies and RF were determined in the sera of 30 patients with RA and 22 patients with HCV-related polyarthropathy. Anti-CCP antibodies were positive in 83.3% of patients with RA and in 4.5% in patients with HCV and polyarthropathy. RF was positive in 90% of RA patients and in 81.1% of HCV patients with polyarthropathy. The anti-CCP antibodies showed higher specificity for RA compared with RF (95.4 vs. 18.2%). However, the sensitivity of anti-CCP was comparable to that of RF (83.3 vs. 90%). In conclusions, anti-CCP antibodies are reliable laboratory markers to differentiate between RA and HCV-related polyarthropathy.
20668905 Prevalence of reactivation of hepatitis B virus replication in rheumatoid arthritis patien 2011 Feb Reactivation of hepatitis B involves the reappearance of active necroinflammatory liver disease after an inactive hepatitis B surface antigen (HBsAg) carrier state or resolved hepatitis B, occurring during or after immunosuppression therapy or chemotherapy. We prospectively investigated the reactivation rate for hepatitis B virus (HBV) DNA replication in cases of rheumatoid arthritis (RA) with resolved hepatitis B. HBV markers were evaluated in 428 RA patients. Patients with positive findings of HBsAg or HBV DNA at enrolment were excluded. The study population comprised 422 RA patients, with resolved hepatitis B diagnosed in 135 patients based on HBsAg-negative and antihepatitis B core antibody/antihepatitis B surface antibody-positive results. HBV DNA was measured every 3 months in this group, and if HBV DNA became positive after enrolment, measurement was repeated every month. HBV DNA became positive (≥3.64 log copies/mL) in 7 of 135 patients for 12 months. Use of biologic agents was significantly more frequent in patients who developed reactivation of HBV DNA replication (85.7%) than in patients who did not (36.0%, p = 0.008). Hazard ratios for use of biologic agents and etanercept were 10.9 (p = 0.008) and 6.9 (p = 0.001), respectively. RA patients with resolved hepatitis B need careful monitoring when receiving biologic agents, regardless of HBV DNA levels.
19880998 [Progress of research in osteoarthritis. Pharmacological effects of hyaluronan]. 2009 Nov Hyaluronan of high molecular weight is now widely used by intraarticular injection into knee joints in patients with osteoarthritis and rheumatoid arthritis. Proinflammatory cytokines and matrix degradation products (matrikines) increased in osteoarthritic and rheumatoid arthritic joints induce catabolic enzymes such as collagenase and aggrecanase that cause cartilage degradation. The recent studies have shown that hyaluronan inhibits the catabolic actions by cytokines and matrikines via its cell surface receptors. This paper describes the chondroprotective effects of hyaluronan on osteoarthritis and rheumatoid arthritis.