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ID PMID Title PublicationDate abstract
18440832 Inter-rater reliability of an arthritic glenoid morphology classification system. 2008 Jul To our knowledge, no independent analysis of the inter-rater agreement of the widely used Walch classification for osteoarthritic glenoid morphology has been performed. The computed tomography scans of 24 shoulders with primary osteoarthritis were used by 4 experienced shoulder surgeons to classify the glenoids independently according to Walch et al. The weighted kappa statistic was calculated to determine the inter-rater and intrarater agreement among observers. The overall inter-rater agreement for the Walch classification was fair (kappa = 0.37) when classified into the 5 types (A1, A2, B1, B2, and C). Agreement for the various subclassifications was as follows: A1, kappa = 0.22; A2, kappa = 0.33; B1, kappa = 0.17; B2, kappa = 0.32; and C, kappa = 0.86. When the classification system was simplified to just the 3 major types (A, B, and C), overall agreement was moderate (kappa = 0.44). Agreement for each type was moderate for A (kappa = 0.59) and B (kappa = 0.59) and almost perfect for C (kappa = 0.89). Overall intrarater agreement was fair (kappa = 0.37). We conclude that only fair agreement was found among experienced shoulder surgeons when classifying arthritic shoulders using the classification system of Walch et al. A glenoid classification scheme that relies more upon glenoid morphology and less upon humeral head position may demonstrate greater observer agreement and, therefore, may offer greater value.
16508929 Association of chronic inflammation, not its treatment, with increased lymphoma risk in rh 2006 Mar OBJECTIVE: Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective. METHODS: We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments. RESULTS: The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas. CONCLUSION: Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.
18663553 The changes in serum chemokines following leflunomide therapy in patients with rheumatoid 2009 Jan We undertook this study to evaluate the effects of leflunomide, an oral pyrimidine synthesis inhibitor, on the serum chemokine levels in patients with active rheumatoid arthritis (RA) who were refractory to treatment with methotrexate (MTX) or did not tolerated MTX treatment. RA patients were supposed to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally for the 12 months). Serum concentrations of RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) were assessed by enzyme-linked immunosorbent assay before and after 3, 6, 9, and 12 months of treatment with leflunomide. Three months therapy with leflunomide caused reduction in serum RANTES and MCP-1 (in both cases, p < 0.001) levels. Decrease in the concentration of these chemokines persisted until the end of the study period but was less significant. In the case of IL-8, its serum levels significantly diminished after 6 months of therapy with leflunomide (p < 0.01) and remained stable to the end of the study. Changes in serum chemokine levels were accompanied by significant decrease of disease activity score (DAS; p < 0.001). Prior to the first dose of leflunomide, serum concentrations of studied chemokines correlated with marker of RA activity such as the erythrocyte sedimentation rate and IL-8 level with DAS. Furthermore, we demonstrated significant correlations between serum levels of RANTES, MCP-1, and IL-8. During study period, such associations were far less or not significant. Leflunomide, beside a clinical improvement, reduce serum chemokines concentrations in RA patients. Leflunomide seems to be an effective treatment for RA, alternative to current therapies.
17765835 Hallux metatarsophalangeal joint fusion for the rheumatoid forefoot. 2007 Sep Forefoot problems in patients who have rheumatoid arthritis are common. The progressive joint destruction causes a redistribution of weight about the forefoot, with a diminished weightbearing capacity of the first metatarsophalangeal (MTP) joint. Changes around the first MTP joint include synovitis, joint instability with subluxation, and arthritic change. Hallux MTP fusion in patients who have rheumatoid arthritis acts to permanently restore alignment and restore the medial column support of the foot, while at the same time enabling the first MTP to resume its original weightbearing role. Rheumatoid hallux MTP fusion and its rationale are reviewed.
18507161 [Characteristics of responses of rabbit joint structures to intraarticular introduction of 2008 Mar On a model of autoimmune arthritis in rabbits, reduction of inflammatory-destructive process manifestation was observed in all joint tissues under the influence of the intraarticular introduction of calcitonin. Improving metabolic processes in the matrix of tissue-connecting elements of a joint, this specimen inhibits the inflammatory destruction of the subchondral bone and hyaline cartilage in conditions of experimental rheumatoid inflammation.
17787050 Functional Health Assessment Questionnaire (HAQ) and Psychological HAQ Are Associated with 2007 Sep OBJECTIVE: To evaluate the association between clinical, demographic, and psychological factors and the functional Health Assessment Questionnaire (HAQ) and psychological HAQ (PSHAQ) in patients with rheumatoid arthritis (RA). METHODS: After a mean followup time of 7 years after diagnosis, 112 patients with RA were asked to fill out the HAQ and the PSHAQ. Several clinical variables [erythrocyte sedimentation rate (ESR), visual analog scale (VAS) pain, VAS general well-being, Thompson joint score, and morning stiffness] had been assessed at diagnosis and at followup. In addition, the Impact of Rheumatic diseases on General health and Lifestyle questionnaire, comprising different domains of psychological distress, was assessed at diagnosis. Spearman correlations were calculated to determine associations between functional HAQ and clinical and psychological variables at baseline and to determine the associations between clinical variables and the HAQ and PSHAQ score at followup. Univariate logistic regression analyses were performed to identify possible predictors at diagnosis for a worse HAQ score and PSHAQ score (score > 1) at followup. RESULTS: At followup the functional HAQ score was associated with all clinical variables, whereas the PSHAQ was only associated with more subjective patient related variables (VAS pain, VAS general well-being, and morning stiffness). The final model of the multivariate regression analyses to predict a worse HAQ score at followup only included worse functional ability [odds ratio (OR) 2.63, 95% confidence interval (CI) 1.30-5.32, p = 0.007]. Anxiety (OR 1.13, 95% CI 1.03-1.24, p = 0.007) and a lower ESR value (OR 0.98, 95% CI 0.96-1.00, p = 0.05) assessed at diagnosis were included into the final model as predictors for a high PSHAQ score. CONCLUSION: Overall, the HAQ score, reflecting limitations of daily functioning, is a good representation of disease activity at diagnosis and after a mean disease duration of 7 years, whereas PSHAQ is not.
17266100 HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardi 2007 Feb 15 OBJECTIVE: Cardiovascular (CV) disease is the most common cause of mortality in patients with rheumatoid arthritis (RA). We assessed the contribution of epidemiologic features, clinical features, routine laboratory markers of inflammation, and HLA-DRB1 alleles to CV mortality in patients with RA prospectively followed at a single referral center in Spain. METHODS: Patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo between March and September 1996 were included. HLA-DRB1 phenotype, epidemiologic data, and clinical data were assessed at that time. Patients were prospectively followed and clinical records were examined until patient's death or September 1, 2005. RESULTS: A total of 182 consecutive patients were assessed. Compared with the general Spanish population, the age- and sex-standardized mortality ratio by CV cause was 1.78. CV mortality adjusted by age at disease onset and sex was associated with chronic inflammation determined by C-reactive protein level (CRP; hazard ratio [HR] 1.14, P < 0.001) and erythrocyte sedimentation rate (ESR; HR 1.05, P = 0.003). Patients with HLA-DRB1*04 shared epitope alleles (HR 4.15, P = 0.030), in particular those HLA-DRB1*0404 positive (HR 6.65, P = 0.002), had increased risk of CV mortality. Increased risk of CV events was also associated with CRP level (HR 1.09, P = 0.001), ESR (HR 1.03, P = 0.003), and HLA-DRB1*0404 (HR 4.47, P = 0.002). CONCLUSION: Our results suggest that a chronically high inflammatory response in genetically predisposed individuals promotes an increased risk of CV events and CV mortality in RA.
17962368 Serum amyloid A inhibits apoptosis of human neutrophils via a P2X7-sensitive pathway indep 2008 Jan Neutrophil apoptosis is important for the termination of inflammatory reactions, in that it ensures placid clearance of these potently cytotoxic cells. Various proinflammatory cytokines delay neutrophil apoptosis, which may result in accumulation of these cells, sometimes accompanied by tissue destruction, potentially leading to various inflammatory disease states. Rheumatoid arthritis (RA) is characterized frequently by elevated levels of the acute-phase reactant serum amyloid A (SAA) in circulation and in tissues. SAA is emerging as a cytokine-like molecule with the ability to activate various proinflammatory processes, many of which involve signaling via the formyl peptide receptor-like 1 (FPRL1). In this study, we show that SAA, purified from plasma from RA patients or in recombinant form, suppressed apoptosis of human neutrophils. Blocking FPRL1 did not lessen the antiapoptotic effects of SAA, implying the action of a receptor distinct from FPRL1. In contrast, antagonists of the nucleotide receptor P2X7 abrogated the antiapoptotic effect of SAA completely but did not block intracellular calcium transients evoked by SAA stimulation. Based on these results and also the finding that blocking P2X7 inhibited antiapoptotic actions of unrelated stimuli (LPS and GM-CSF), we propose that P2X7 is a general mediator of antiapoptotic signaling in neutrophils rather than a bona fide SAA receptor.
17121034 [Correlations between diagnostic information and therapeutic efficacy in rheumatoid arthri 2006 Oct OBJECTIVE: To explore the correlations between diagnostic information and therapeutic efficacy in rheumatoid arthritis (RA) with decision tree model analysis. METHODS: Three hundred and ninety seven patients came from 9 clinical centers were randomly divided into the Western medicine (WM) group (n=194) treated with non-steroidal anti-inflammatory drugs and slow-acting antirheumatic drug and the Chinese medicine (CM) group (n=203) with basic therapy and syndrome-differentiation dependant TCM treatment. TCM and WM diagnostic information were collected. The ACR 20 was used for efficacy evaluation and the information of patients before treatment was analyzed by SAS 8.2 statistical package. Through single-factor exploratory analysis, odds ratio of efficacy and variable was calculated taken P < 0.2 as the including criteria for data mining analysis with decision tree model. All data were classified into the training set (75%) and verifying set (25%) with efficacy as the variable for layering to make further verification of the data-mining analysis. RESULTS: Twenty variables were included in the CM group and 26 in the WM group in the data-mining model. In the former, 9 variables were positively correlated to the efficacy, including degree of arthralgia, tenderness and morning stiffness, number of swollen joint, and joint with tenderness, levels of IgM, rheumatoid factor (RF), C-reactive protein (CRP), and total assessment from doctor; and disease duration and degree of nocturnal polyuria were negatively correlated to that. While in the latter, 8 were positively correlated to the efficacy, including erythrocyte sedimentation rate (ESR), sour and weak waist and knees, white fur in tongue, joint ache and stiffness, swollen joint, and total assessment from doctor and patient, and red tongue with yellow fur and leucocyte count negatively correlated to it. Data mining with decision tree analysis revealed that different combinations of morning stiffness, slight red tongue, joint tenderness and nocturnal polyuria in the CM group, and those of white fur in tongue, CRP level, leucocyte count and morning stiffness in the WM group showed different efficacy, which were also verified in the randomly chosen verifying set. CONCLUSION: To analyze the correlations between diagnostic information and therapeutic efficacy with decision tree analysis is conformed to the theory of TCM in applying treatment according to syndrome differentiation individually, thus it would contribute to elevate the accuracy of therapy.
16766362 Risk factors for the development of rheumatoid arthritis. 2006 May There is increasing interest in attempting to understand what the risk factors are that lead to the development of rheumatoid arthritis (RA). Twin studies have proved a genetic role but also quantified the non-genetic risk. There is thus scope for identifying environmental predictors that might offer a strategy to prevent the disease. Changes in the female hormonal environment such as in pregnancy, breastfeeding and the use of the oral contraceptive (OC) pill appear to have a role. Of the traditional lifestyle exposures, cigarette smoking has been associated with a consistently increased risk that might also apply to the passive inhalation of smoke. Occupation probably has a minor influence, although exposure to silica dust is of aetiological importance. Recent studies have highlighted a role for diet, with suggestions that diets high in caffeine, low in antioxidants and high in red meat may contribute to an increased risk. The most plausible environmental exposure is infection and although several decades of study have produced few definitive candidate organisms, Epstein-Barr virus (EBV) remains an interesting target.
18265799 [The diagnostic accuracy of anti-citrullin antibody assessment in the diagnosis of patient 2008 Jan 12 OBJECTIVE: To determine whether assessment of antibodies directed against citrullin provides additional value in the diagnosis of rheumatoid arthritis (RA) in general practice. DESIGN: Retrospective. METHODS: In a 6-month period in 2004 (May-December), all sera sent to our laboratory for assessment of rheumatoid factor (RF-IgM), were also analysed for the presence of antibodies directed against citrullinated fibrinogen (anti-citrullin). We analysed 691 sera sent in by general practitioners using a homemade assay. To determine the disease classification, general practitioners were asked to provide information pertaining to the American College of Rheumatology disease classification criteria. The response was 97.6%. For patients who were referred to a rheumatologist in the last 2 years (December 2004-December 2006), the diagnosis of the rheumatologist was also considered in the analysis. RESULTS: A total of 28 patients (4%) were diagnosed with rheumatoid arthritis. Only 25% of these patients were positive for anti-citrullin, and only 25% were positive for RF-IgM. These 2 groups only partially overlapped. The positive and negative predictive values of anti-citrullin were 36 and 96%, respectively. CONCLUSION: The presence of anti-citrullin provided no additional value compared to rheumatoid factor in classifying RA in a general practice population.
16447061 Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis. 2006 Sep Rheumatoid arthritis (RA) is commonly associated with decreased bone mineral density (BMD) due to numerous factors. BsmI polymorphism of the vitamin D receptor (VDR) gene has been implicated in the pathogenesis of osteoporosis. Vitamin D has several immunomodulatory effects and thus may play a role in the course of arthritis. However, little data is available on the possible relationship between RA and VDR gene polymorphisms. In this study, the frequency of BsmI polymorphism genotypes were compared with that found in other countries. In this study, 64 RA patients and 40 healthy controls were tested for VDR gene BsmI polymorphism genotypes. Frequencies of B and b alleles were associated with markers of bone metabolism and RA. Among control subjects, the frequency of the BB genotype is relatively high (27.5%). In RA with secondary osteopenia/osteoporosis the BB genotype was more rare, the bb was more common than in control subjects. Markers of bone metabolism were associated with the B allele. RA patients carrying the B allele had lower BMD and increased bone loss over 1 year. The B allele was also correlated with increased osteoclast and osteoblast function, as determined by the assessment of biochemical markers of bone metabolism. Rheumatoid factor titer, which is an independent marker for disease progression in RA, was higher in bb patients. Our data suggest, that the imbalance in B and b allele expression may be involved in the pathogenesis of RA-associated osteoporosis. The possible involvement of vitamin D and VDR gene polymorphisms in the development and progression of RA needs further elucidation.
17671742 Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibrobla 2007 Sep Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of anti-apoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumin-induced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E(2) synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.
16646979 Osteogenic protein 1 in synovial fluid from patients with rheumatoid arthritis or osteoart 2006 The measurement of body fluid levels of biochemical markers in joint tissues has begun to provide clinically useful information. Synovial fluid (SF) plays an important role in articular joint lubrication, nutrition, and metabolism of cartilage and other connective tissues within the joint. The purpose of our study was to identify and characterize osteogenic protein 1 (OP-1) in SF from patients with rheumatoid arthritis (RA) or with osteoarthritis (OA) and to correlate levels of OP-1 with those of hyaluronan (HA) and antigenic keratan sulfate (AgKS). SF was aspirated from the knees of patients with either RA or OA and from the knees of asymptomatic organ donors with no documented history of joint disease. The presence of detectable OP-1 in SF was demonstrated by western blots with specific anti-pro-OP-1 and anti-mature OP-1 antibodies. Measurement of levels of OP-1, HA and AgKS was performed using ELISAs. OP-1 was identified in human SF in two forms, pro-OP-1 and active (mature) OP-1--mature OP-1 being detected only in SF from OA patients and RA patients. Levels of OP-1 and HA were higher in RA patients than in OA patients and asymptomatic donors, while the level of AgKS was highest in SF from asymptomatic donors. Statistically significant differences were found between SF levels of OP-1 in RA and OA patients and between SF levels of AgKS among the three groups tested. The SF content of OP-1 tended to correlate positively with HA levels, but negatively with AgKS concentrations. In conclusion, the results of this study suggest that measurement of OP-1 in joint fluid may have value in the clinical evaluation of joint disease processes.
18336871 Role of interleukin-6 in the anemia of chronic disease. 2009 Apr OBJECTIVES: To review evidence supporting the involvement of interleukin-6 in the pathophysiology of anemia of chronic disease, to discuss the possible molecular mechanisms driving this condition in patients with end-stage renal disease and rheumatoid arthritis, and to review clinical manifestations in these patients. METHODS: A literature search was performed using MEDLINE and the reference lists of relevant review articles. The following key words were used in the MEDLINE search: interleukin-6, "anemia of chronic disease" OR "anemia of inflammation," "pathophysiology," "end-stage renal disease," and "rheumatoid arthritis." The search was limited to English-language articles. RESULTS: Interleukin-6 is a multifunctional cytokine that regulates the hepatic acute-phase response, the immune response, inflammation, and hematopoiesis. Interleukin-6 appears to be the central mediator of anemia of chronic disease in a range of inflammatory diseases, including end-stage renal disease and rheumatoid arthritis, through increased generation of hepcidin and the resultant alterations in iron metabolism. Clinically, patients with anemia of chronic disease are more likely to experience increased disease severity and duration than patients who have chronic disease without anemia. CONCLUSIONS: The integral role of interleukin-6 in the pathogenesis of anemia of chronic disease suggests that it could be an important therapeutic target. Currently available treatments target interleukin-1, and tumor necrosis factor-alpha and its receptors, and have been only partially successful. Given the complexity of the cytokine pathways that are involved in the pathogenesis of inflammatory disease, further studies are required to test other molecular targets.
16798046 Recommendations of the French Society for Rheumatology. TNFalpha antagonist therapy in rhe 2006 Jul OBJECTIVES: To develop recommendations for TNFalpha-antagonist therapy in patients with rheumatoid arthritis (RA) seen in everyday practice, under the aegis of the French Society for Rheumatology. METHOD: We used the methods recommended by the French Agency for Healthcare Accreditation and Evaluation, the AGREE collaboration, and the European League against Rheumatism (EULAR). The recommendations focus on patient selection, monitoring, and treatment adjustments. RESULTS: Criteria for selecting patients eligible for TNFalpha-antagonist treatment of RA include: 1) a definitive diagnosis of RA; 2) disease activity for longer than 1 month, including presence of objective signs of inflammation; or radiographic progression; 3) previous failure of methotrexate in the highest tolerated dosage or of another disease-modifying antirheumatic drug in patients with contraindications to methotrexate; 4) absence of contraindications to TNFalpha-antagonist therapy. When starting TNFalpha-antagonist therapy 1) a thorough baseline evaluation should be conducted; 2) any of the three available agents can be used, as no differences in efficacy have been identified in patient populations; 3) concomitant methotrexate therapy is recommended regardless of the TNFalpha antagonist used; and 4) patients should receive standardized follow-up at regular intervals. Treatment adjustments should be based on the following: 1) the treatment objective is achievement of a EULAR response; 2) when such a response is not achieved, the dosage or dosing interval can be changed, or the patient can be switched to another TNFalpha antagonist; 3) in patients who experience intolerance to a TNFalpha antagonist, another TNFalpha antagonist may be tried, depending on the nature of the adverse event; 4) occurrence of a remission should lead to a reduction in symptomatic medications, most notably glucocorticoids where used; in the event of a prolonged remission, either the TNFalpha antagonist or the concomitant disease-modifying antirheumatic drug may be reduced. CONCLUSION: These recommendations are intended to help physicians use TNFalpha antagonists in their everyday practice with RA patients. They do not constitute regulations.
17414949 Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis. 2007 May PURPOSE OF REVIEW: The calcineurin inhibitors cyclosporine and tacrolimus are important treatments for patients with active rheumatoid arthritis, especially in cases of resistance or intolerance to methotrexate or other disease-modifying antirheumatic drugs. Here, we discuss the mechanism, efficacy and safety of cyclosporine and tacrolimus in the treatment of rheumatoid arthritis. RECENT FINDINGS: Recent clinical trials of cyclosporine have shown the advantages of its combination with methotrexate, glucocorticoids and leflunomide in the treatment of active rheumatoid arthritis. In Japan, tacrolimus monotherapy was found to be quite effective and combination therapy with methotrexate had positive results in an American study. The inhibitory effects of both drugs not only on T lymphocytes, but also on human osteoclast formation, have been demonstrated in basic studies. SUMMARY: Cyclosporine and tacrolimus are clinically available disease-modifying antirheumatic drugs. Numerous clinical studies have shown the usefulness of these calcineurin inhibitors in monotherapy and also when combined with methotrexate. Although these drugs have similar effects, there are some differences in adverse reactions.
17306036 Mesenchymal stromal cells. Nurse-like cells reside in the synovial tissue and bone marrow 2007 A major question concerning the immunopathology of rheumatoid arthritis is why the disease is localized to particular joints. A possible explanation could be the presence within the synovium of cells that foster inflammation or easy accessibility of the synovium to migratory disease enhancing cells. Within both the bone marrow and the synovium, fibroblastic stromal cells play an important role in supporting the differentiation and survival of normal cells, and also contribute to the pathologic processes. Among fibroblastic stromal cells in synovial tissue and bone marrow, nurse-like cells are a unique population having the specific capacity to promote pseudoemperipolesis (adhesion and holding beneath) of lymphocytes, and also the ability to promote the growth and function of some populations of lymphocytes and monocytes. Nurse-like cells could therefore contribute to the immunopathogenesis of rheumatoid arthritis, and may contribute to the localization of inflammation within specific joints. The present review considers the evidence that supports these possibilities.
18226183 Inflammation, carotid intima-media thickness and atherosclerosis in rheumatoid arthritis. 2008 Carotid intima-media thickness (cIMT) reflects early atherosclerosis and predicts cardiovascular events in the general population. An increased cIMT is present in patients with rheumatoid arthritis, compared with control individuals, from the early stages of the disease and is thought to indicate accelerated atherosclerosis, but direct evidence is not available. Whether cIMT is susceptible to rapid and potentially reversible change depending on the intensity of inflammation in states of high-grade systemic inflammation, such as rheumatoid arthritis, remains unknown. If this is the case, an increased cIMT in such disease states may not reflect structural vessel wall damage, and may not be a good predictor of future cardiovascular events in these particular populations. Prospective, long-term, longitudinal studies are needed to address these questions.
18388160 MRI bone oedema is the strongest predictor of subsequent radiographic progression in early 2009 Mar OBJECTIVE: To identify predictors of radiographic progression in a 2-year randomised, double-blind, clinical study (CIMESTRA) of patients with early rheumatoid arthritis (RA). METHODS: Patients with early RA (n = 130) were treated with methotrexate, intra-articular betamethasone and ciclosporin/placebo-ciclosporin. Baseline magnetic resonance imaging (MRI) of the wrist (wrist-only group, n = 130) or MRI of wrist and metacarpophalangeal (MCP) joints (wrist+MCP group, n = 89) (OMERACT RAMRIS), x-ray examination of hands, wrists and forefeet (Sharp/van der Heijde Score (TSS)), Disease Activity Score (DAS28), anti-cyclic citrullinated peptide antibodies (anti-CCP), HLA-DRB1-shared epitope (SE) and smoking status were assessed. Multiple regression analysis was performed with delta-TSS (0-2 years) as dependent variable and baseline DAS28, TSS, MRI bone oedema score, MRI synovitis score, MRI erosion score, anti-CCP, smoking, SE, age and gender as explanatory variables. RESULTS: Baseline values: median DAS28 5.6 (range 2.4-8.0); anti-CCP positive 61%; radiographic erosions 56%. At 2 years: DAS28 2.0 (0.5-5.7), in DAS remission: 56%, radiographic progression 26% (wrist+MCP group, similar for wrist-only group). MRI bone oedema score was the only independent predictor of delta-TSS (wrist+MCP group: coefficient = 0.75 (95% CI 0.55 to 0.94), p<0.001; wrist-only group: coefficient = 0.59 (95% CI 0.40 to 0.77), p<0.001). Bone oedema score explained 41% of the variation in the progression of TSS (wrist+MCP group), 25% in wrist-only group (Pearson's r = 0.64 and r = 0.50, respectively). Results were confirmed by sensitivity analyses. CONCLUSION: In a randomised controlled trial aiming at remission in patients with early RA, baseline RAMRIS MRI bone oedema score of MCP and wrist joints (and of wrist only) was the strongest independent predictor of radiographic progression in hands, wrists and forefeet after 2 years. MRI synovitis score, MRI erosion score, DAS28, anti-CCP, SE, smoking, age and gender were not independent risk factors. TRIAL REGISTRATION NUMBER: NCT00209859.