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ID PMID Title PublicationDate abstract
18511473 Resistin in serum is associated with higher levels of IL-1Ra in post-menopausal women with 2008 Jul OBJECTIVES: The aim of this study was to investigate associations between serum levels of resistin, an adipokine and markers of inflammation, bone metabolism, plasma lipids and kidney function in post-menopausal RA patients and to evaluate if HRT during 2 yrs affected resistin levels. METHODS: Eighty-eight women were randomly allocated to receive HRT, vitamin D(3) and calcium or vitamin D(3) and calcium alone. Serum levels of resistin, IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-6 soluble receptor, TNF-alpha were measured by ELISA, markers of bone metabolism, carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen by RIA, ESR, CRP, Hb, creatinine and lipids by standard laboratory techniques, BMD and total lean mass (TLM) by DXA and joint destruction by Larsen score. Resistin was also measured in 42 healthy control women. RESULTS: There was no difference in resistin concentration between patients and healthy controls. Resistin was significantly correlated with IL-1Ra, CRP, TNF-alpha, ICTP, glucocorticosteroids and Larsen score and inversely with BMD, hip and with TLM. In multiple regression analysis, IL-1Ra, TLM and use of corticosteroids remained determinants of resistin. Patients treated with HRT displayed significant increase in resistin compared with controls in the first but not the second year. CONCLUSIONS: Resistin was associated with increased inflammation, particularly by the acute-phase reactant IL-1Ra antagonizing IL-1beta, joint destruction, glucocorticosteroids and with reduced BMD and TLM. These findings suggest resistin being a significant mediator in the inflammatory process in RA. Further studies examining the mechanisms behind the relation between resistin and IL-1Ra are encouraged. HRT does not seem to have important long-term effect on resistin.
17705417 Proteomic analysis of peripheral blood mononuclear cells: selective protein processing obs 2007 Sep In a comparative proteome analysis of peripheral blood mononuclear cells (PBMCs), we analyzed 130 two-dimensional gels obtained from 33 healthy control individuals and 32 patients diagnosed with rheumatoid arthritis (RA). We found 16 protein spots that are deregulated in patients with RA and, using peptide mass fingerprinting and Western blot analyses, identified these spots as belonging to 9 distinct proteins. A hierarchical clustering procedure organizes the study subjects into two main clusters based on the expression of these 16 protein spots, one that contains mostly healthy control individuals and the other mostly RA patients. The majority of the proteins differentially expressed in RA patients when compared with healthy controls can be detected as protein fragments in PBMCs obtained from RA patients. This set of deregulated proteins includes several factors that have been shown to be autoantigens in autoimmune diseases.
18772191 Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis 2009 Jul OBJECTIVES: Abatacept is the only agent currently approved to treat rheumatoid arthritis (RA) that targets the co-stimulatory signal required for full T-cell activation. No studies have been conducted on its effect on the synovium, the primary site of pathology. The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFalpha) blocking therapy. METHODS: This first mechanistic study incorporated both dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and arthroscopy-acquired synovial biopsies before and 16 weeks after therapy, providing tissue for immunohistochemistry and quantitative real-time PCR analyses. RESULTS: Sixteen patients (13 women) were studied; all had previously failed TNFalpha-blocking therapy. Fifteen patients completed the study. Synovial biopsies showed a small reduction in cellular content, which was significant only for B cells. The quantitative PCR showed a reduction in expression for most inflammatory genes (Wald statistic of p<0.01 indicating a significant treatment effect), with particular reduction in IFNgamma of -52% (95% CI -73 to -15, p<0.05); this correlated well with MRI improvements. In addition, favourable changes in the osteoprotegerin and receptor activator of nuclear factor kappa B levels were noted. DCE-MRI showed a reduction of 15-40% in MRI parameters. CONCLUSION: These results indicate that abatacept reduces the inflammatory status of the synovium without disrupting cellular homeostasis. The reductions in gene expression influence bone positively and suggest a basis for the recently demonstrated radiological improvements that have been seen with abatacept treatment in patients with RA.
17562686 Modelling the cost effectiveness of TNF-alpha antagonists in the management of rheumatoid 2007 Aug OBJECTIVE: To evaluate the cost effectiveness of TNF-alpha antagonist therapies for rheumatoid arthritis (RA) in the United Kingdom using data from the British Society for Rheumatology Biologics Registry (BSRBR). METHODS: A simulation model is constructed to quantify the cost effectiveness of the TNF-alpha antagonist therapies (infliximab, etanercept and adalimumab) as a group versus traditional disease-modifying anti-rheumatic drugs, with a time horizon over the full patient lifetime. Participants are UK NHS patients in the BSRBR with RA who have failed at least two traditional disease-modifying anti-rheumatic drugs. The BSRBR aims to recruit all RA patients starting on a TNF-alpha antagonist agent and follows them 6 monthly via consultant and patient administered questionnaires. Data collected include disease activity scores (DAS28), the Health Assessment Questionnaire and the SF-36. Costs include drug, monitoring and hospitalisations. Benefits are measured in disability and quality of life improvements. The main outcome measure is the incremental cost per quality adjusted life-year gained (discounted). RESULTS: The basecase cost per quality adjusted life-year gained by using TNF-alpha antagonist therapies is estimated at pound23 882, with probabilistic uncertainty analysis suggesting that the probability that treatments are below 30,000 pounds per QALY is around 84%. The results are most sensitive to assumptions concerning long-term disability progression, discount rates and the validity or otherwise of SF6D derived utility measures. Subgroup analysis, monotherapy versus combination with methotrexate, and a limited analysis of sequential therapy with two TNF-alpha antagonist agents, suggest cost-effectiveness ratios around 20,000 pounds to 30,000 pounds. CONCLUSIONS: The BSRBR data provide valuable evidence for estimating cost-effectiveness. The analysis concludes that current policies and practice for the use of TNF-alpha antagonist therapies, after RA patients have failed at least two traditional disease-modifying anti-rheumatic drugs, appear cost-effective in the context of the NICE re-appraisal of 2006 for England and Wales, thus supporting their decision to continue their reimbursement. Decision-makers worldwide might adapt this analysis because differential costs, discount rates and other factors could affect results. There remains uncertainty, particularly on long-term disease progression. Further data collection using the BSRBR is recommended, together with a revision to this analysis when data become available.
18317877 Maximum intensity projection as a tool to diagnose early rheumatoid arthritis. 2008 In this study, we investigated the usefulness of contrast-enhanced MRI with maximum intensity projection (MIP) as a convenient tool for detecting early rheumatoid arthritis (RA). A total of 21 patients with undiagnosed arthritis of the hands at the initial visit were enrolled in a prospective study over a 1-year period. The number of swollen joints found during physical examination at this first visit, the results of serological tests and the number of synovitis joints diagnosed on MIP images were compared between the RA group and non-RA group. Of the 21 patients, 17 (81%) from the initial study who were followed up for an additional 1 year entered this study. Of these, 5 met the conditions for diagnosis of RA during follow-up, and 12 did not. MIP images were used to review the arthritis of RA patients, and a significant difference was found in the number of synovitis inflammations detected with MIP images when compared with findings after physical examinations. The two criteria of positive CARF and/or anti-CCP antibody and symmetrical synovitis in bilateral hands on MIP images allowed the prediction of RA with 100% sensitivity and 75% specificity. Thus, MIP is a useful tool for making early diagnosis of RA because it yields clear visualization even with just one image.
18848428 The relationship between increased hip range of motion, wear, and locking mechanism failur 2009 Sep We performed both clinical and radiographic evaluations of 178 patients (190 hips) who had undergone cementless total hip arthroplasties using Harris-Galante I/II porous cups after an average 12-year follow-up period (range, 8-18 years). We revised 15 Harris-Galante I/II porous cups (7.8%), and the locking mechanism was broken in 10 revised cups (67%). There was a significant association between locking mechanism failure and linear polyethylene wear. We observed a significant positive correlation between linear polyethylene wear and increased ranges of motion such as flexion, adduction, and external rotation at the last follow-up visit after the primary operation. Increased ranges of motion seen in Asians induced higher linear polyethylene wear and locking mechanism failure due to impingement of the neck and cup.
19032807 Are the C-reactive protein values and erythrocyte sedimentation rate equivalent when estim 2008 Sep A formula for calculating disease activity score with 28 joint counts (DAS28) with C-reactive protein (CRP) instead of the erythrocyte sedimentation rate (ESR) has been proposed. OBJECTIVE: Here we analyze the factors that contribute to the differences in the DAS28 when calculated using either the ESR (DAS28-ESR) or the CRP values (DAS28-CRP). METHODS: We analyzed the data from 587 visits made by 220 patients with early arthritis. The age at the onset of the disease was 51+/-16 years old and 76.3% of the patients were women. The disease evolution at the first visit was 5 months and at each visit information related to several variables was collected, including that necessary to calculate the DAS28-ESR and DAS28-CRP. We defined a new variable DIFDAS=DAS28-ESR-DAS28-CRP to analyze which independent variables account for differences between the two indexes. RESULTS: There was a correlation between the two indexes of 0.91 (p<0.0001), although the DAS28-ESR value obtained was higher than that of DAS28-CRP at approximately 90% of the visits. Significantly, the difference between both indexes was higher than 0.6 in 44% of the visits studied. A multivariate analysis showed that female gender and disease duration were associated with the higher values obtained for DAS28-ESR when compared to those of DAS28-CRP. CONCLUSION: Our data show that DAS28-ESR and DAS28-CRP are not fully equivalent, because the former usually produces higher values. This finding is particularly relevant in females and patients with a long disease duration.
18622574 Rheumatologists' knowledge, attitude and current management of fatigue in patients with rh 2008 Dec To describe rheumatologists' knowledge, attitude and current management of fatigue in patients with rheumatoid arthritis (RA), a postal questionnaire was sent to all rheumatologists (N = 204) and trainees (N = 49), members of the Dutch Society of Rheumatology. The overall response rate was 44% (N = 110). In general, rheumatologists' knowledge about RA-related fatigue was in accordance with the literature but they perceive a lack of their own knowledge about aetiology and evidence-based interventions to prevent and treat fatigue. The majority of the rheumatologists believe that fatigue is a multi-disciplinary diagnosis and is preferably managed by the nurse specialist (34%). Assuming that the patient will raise the issue, most of the rheumatologists pay attention to fatigue during the first consultation and less often during follow-up consultations. There is a need for knowledge about causes and treatments for RA-related fatigue to ensure that patient outcomes are improved.
19169297 [Articular diseases and uveitis]. 2008 Ocular inflammation is a common clinical manifestation related to several autoimmune systemic disorders, specially spondyloarthropaties. In this group, there are different clinical diseases that are related to special uveitic patterns. Several discriminative patterns have been defined that closely link uveitis with certain systemic or ophthalmic diseases. Unilateral recurrent anterior acute uveitis is the most frequent form of uveitis related to spondyloarthropaties, and is sometimes the initial manifestation of an undiagnosed spondyloarthropaty. The collaboration of ophthalmologists, rheumatologists and internal medicine specialists is very important for the correct management and treatment of these patients.
16508971 Antigen-induced, tolerogenic CD11c+,CD11b+ dendritic cells are abundant in Peyer's patches 2006 Mar OBJECTIVE: Although oral tolerance is a well-known phenomenon, the role of dendritic cells (DCs) is not well characterized. This study was conducted to better understand the differential role played by each Peyer's patch DC subset in the induction of oral tolerance to type II collagen (CII) in murine collagen-induced arthritis (CIA). METHODS: CII was fed 6 times to DBA/1 mice beginning 2 weeks before immunization, and the effect on arthritis was assessed. We compared the proportion of CD11c+,CD11b+ DCs and CD11c+,CD8alpha+ DCs in the Peyer's patches of CII-fed tolerized and phosphate buffered saline-fed nontolerized mice after the induction of CIA. The immunosuppressive properties of each DC subset were determined using fluorescence-activated cell sorter analysis for intracellular interleukin-10 (IL-10) and IL-12 and mixed lymphocyte culture. The ability of each DC subset to induce CD4+,CD25+ T regulatory cells was also examined. Mice were injected with CII-pulsed CD11c+,CD11b+ DCs isolated from Peyer's patches of tolerized mice, and the effect on CIA was examined. RESULTS: The severity of arthritis was significantly lower in tolerized mice. The proportion of CD11c+,CD11b+ DCs was increased in the Peyer's patches of tolerized mice and those DCs exhibited immunosuppressive characteristics, such as increased IL-10 production, inhibition of T cell proliferative responses to CII, and CD4+,CD25+ regulatory T cell induction. Furthermore, the CD11c+,CD11b+ DCs suppressed the severity of arthritis upon adoptive transfer. CONCLUSION: Our observations demonstrate that CD11c+,CD11b+ DCs, which are abundant in Peyer's patches during the induction of oral tolerance to CII, are crucial for the suppression of CIA and could be exploited for immunotherapy of autoimmune diseases.
18776783 The centralization of extensor tendons during wrist surgery. 2008 Sep After a wrist surgery in patients with rheumatoid arthritis, the extensor tendons have a tendency to shift toward the ulnar side of the wrist. This is caused by the dorsal tenosynovectomy, disruption of extensor retinaculum, and exteriorization and anatomical orientation of the superficial group of forearm extensor tendons. This article describes a technique as an adjunct to the wrist surgery, which aims to stabilize and centralize tendons of the fourth dorsal wrist compartment over the midline of the wrist. This is achieved by creating a distally based sling, harvested from the extensor carpi radialis longus tendon, then wrapped around the extensor digitorum communis and the extensor indicis proprius tendons, and finally anchored onto the extensor carpi radialis brevis. This adjunctive procedure is recommended in situations when after the wrist surgery, particularly wrist arthroplasty, tendons of the fourth dorsal wrist compartment tend to lay ulnar to the central axis of the hand.
17117490 Rheumatoid arthritis and spondyloarthropathies: geographical variations in prevalence in F 2007 Jan OBJECTIVE: To determine geographical variation in the prevalence of rheumatoid arthritis (RA) and spondyloarthropathies (SpA) in France. METHODS: The survey sample was drawn from 7 areas of France. Households were randomly selected using the national telephone directory, and an individual within each household was randomly chosen by the next-birthday method. All cases of suspected RA and SpA were confirmed by the patient's rheumatologist or by clinical examination. Standardized estimates of prevalence were compared between regions and groups of regions. RESULTS: In total 15,219 anonymous telephone numbers were selected. An average response rate of 64% led to a total of 9395 respondents included in the study. The highest regional rates of RA were observed in the south (range 0.59-0.66%), and the lowest in the north (range 0.14-0.24%), with a national rate of 0.31% (95% CI 0.18-0.48%). Regional heterogeneity was observed for SpA, with the highest rates in Bretagne (0.47%) and the Sud-Est (0.53%) and a national rate of 0.30% (95% CI 0.17-0.46%). CONCLUSION: This study is the largest of its kind conducted in France. It shows inter-regional variations, mainly in RA, with a higher prevalence in the south of the country. The many potential reasons for the heterogeneity observed, including genetic and environmental factors, warrant further research.
16454702 Chemokines in rheumatic diseases. 2006 Jan Chemotactic cytokines, termed chemokines, mediate the ingress of leukocytes into the inflamed synovium. In this review, authors discuss the role of the most relevant chemokines and chemokine receptors involved in chronic inflammatory rheumatic diseases. Rheumatoid arthritis was chosen as a prototype to discuss these issues, as the majority of studies on the role of chemokines in inflammatory diseases were carried out in arthritis. However, other rheumatic diseases including systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, mixed connective tissue disease, polymyositis/dermatomyositis, antiphospholipid syndrome and systemic vasculitides are also discussed in this context. Apart from discussing the pathogenic role of chemokines and their receptors, authors also review the regulation of chemokine production by other inflammatory mediators, as well as the important relevance of chemokines for antirheumatic therapies.
19226097 Primary ceramic-on-ceramic total hip replacement versus metal-on-metal hip resurfacing in 2008 Nov The purpose of this study was to compare clinical outcomes between ceramic-on-ceramic total hip replacement and metal-on-metal hip resurfacing arthroplasty in comparable groups of young active patients at a 3- to 6-year follow-up. The first 250 patients (mean age, 49.54 years) of a series of 930 resurfacing arthroplasties were compared clinically and functionally with a series of 190 patients (mean age, 46.76 years) with ceramic-on-ceramic uncemented total hip prostheses. The total Harris hip score was 97.9 in the resurfacing group vs 92.1 in the ceramic group. In the resurfacing group, 60.71% had a strenuous activity level vs 30.43% in the ceramic group.
18176869 Organ-specific autoantibodies in patients with rheumatoid arthritis treated with adalimuma 2008 Feb BACKGROUND: Rheumatoid arthritis (RA) is frequently associated with organ or non-organ-specific autoantibodies or overt autoimmune disorders. Aim of our study was to assess the prevalence and concentration of a panel of organ-specific autoantibodies in patients with RA and to evaluate their relationship with clinical manifestations and treatment efficacy. METHODS: Clinical and serological data from 20 patients with active RA (3M/17F), aged from 28 to 80 years and 50 healthy controls were analyzed. All patients fulfilled the 1987 American College of Rheumatology (ACR) classification criteria for RA and were treated with adalimumab and methotrexate. At baseline and after 6 months of therapy we tested anti-thyroid antibodies for thyroperoxidase (TPOAb) and thyroglobulin (TgAb) using an automated immunochemiluminescence assay (Immulite 2000, DPC, Los Angeles, CA), and anti-tissue transglutaminase (anti-tTG) using the ELISA assay (Phadia, Freiburg, Germany). Anti-smooth muscle (SMA), anti-liver kidney microsome (LKM), anti-parietal cells (APCA), anti-mitochondrial (AMA) and anti-liver cytosolic protein type 1 (LC1), anti-adrenal gland (ACA), anti-pancreatic islet (ICA) and anti-steroid-producing cell (stCA) antibodies were analyzed using a commercially available indirect immunofluorescence methods. Statistics were performed by the SPSS statistical software for Windows, using non parametric tests. RESULTS: At baseline 6 out of 20 (30%) patients were positive for TPOAb and 8 (40%) for TgAb. After 6 months of treatment 5 (25%) patients had TPOAb and 8 (40%) TgAb. At baseline and after 6 months of treatment only 1 (5%) patient tested positive for IgA anti-tTG (celiac disease was confirmed by intestinal biopsy), and no patients had IgG anti-tTG. However, in RA patients IgG anti-tTG levels significantly increased during treatment (p = 0.017) and were higher than in healthy individuals both at baseline (p = 0.028) and after 6 months of treatment (p = 0.001). Only 1 (5%) patient was positive for APCA and no patient was positive for the other anti-organ-specific antibodies either at baseline or after 6 months of treatment. CONCLUSION: The prevalence of organ-specific antibodies does not seem to change during anti-TNF treatment in RA patients. However, a slight and probably irrelevant increase of IgG anti-tTG antibody levels was observed.
17644545 Changes in bone mineral density in patients with recent onset, active rheumatoid arthritis 2008 Jun OBJECTIVES: We examined the effects of four different treatment strategies on bone mineral density (BMD) in patients with recently diagnosed, active rheumatoid arthritis (RA) and the influence of disease-related and demographic factors on BMD loss after 1 year of follow-up in the BeSt trial. METHODS: BMD measurements of the lumbar spine and total hip were performed in 342 patients with recent onset RA at baseline and after 1 year. Multivariable regression analyses were performed to determine independent associations between disease and demographic parameters and BMD loss after 1 year. RESULTS: Median BMD loss after 1 year was 0.8% and 1.0% of baseline in the spine and the hip, respectively. No significant differences between the treatment groups, including corticosteroids and the anti-tumour necrosis factor-alpha infliximab, were observed with regard to BMD loss after 1 year of treatment. Joint damage at baseline and joint damage progression according to the Sharp-van der Heijde score were independently associated with more BMD loss after 1 year. The use of bisphosphonates independently protected against BMD loss. CONCLUSIONS: After 1 year of follow-up in the BeSt study, we did not find differences in BMD loss between the four treatment strategies, including high doses of corticosteroids and anti-tumour necrosis factor-alpha. Joint damage and joint damage progression are associated with high BMD loss, which emphasises that BMD loss and erosive RA have common pathways in their pathogenesis.
17080519 Metabolic syndrome and subclinical atherosclerosis in rheumatoid arthritis. 2006 Dec OBJECTIVE: We assessed whether features of metabolic syndrome (MetSyn) were risk factors for subclinical atherosclerosis independent of previously identified determinants of cardiovascular disease in 74 patients with rheumatoid arthritis (RA). We further evaluated the clinical utility of currently recommended MetSyn definitions in the identification of RA patients with subclinical atherosclerosis. METHODS: We investigated the associations of MetSyn features and MetSyn definitions with ultrasonographically determined common carotid artery intima-media thickness (CCA-IMT) and plaque, with adjustment for age, radiographic scores (cumulative inflammation), polymorphonuclear cell counts (current inflammation), or hypothyroidism. RESULTS: The Quantitative Insulin Sensitivity Check Index (QUICKI) (partial R = -0.24 to -0.26, p = 0.04 to 0.02), log triglycerides (partial R = 0.23 to 0.30, p = 0.05 to 0.01), and systolic blood pressure (partial R = 0.22 to 0.30, p = 0.06 to 0.002) were consistently associated with the log CCA-IMT. Log triglycerides (OR 1.04, 95% CI 1.01-1.08, p = 0.02) and the QUICKI (OR 0.22, 95% CI 0.05-0.91, p = 0.03) were associated with plaque after adjusting for cumulative inflammation. Hypertension (blood pressure > or = 130/85 mm Hg or drug treatment for hypertension) was consistently associated with CCA-IMT (p = 0.05 to 0.0003) and plaque (p = 0.03 to 0.006). The WHO-defined MetSyn was associated with CCA-IMT (p = 0.08 to 0.04) but not with plaque (p > or = 0.1). The National Cholesterol Education Program-defined MetSyn was not associated with CCA-IMT or plaque (p > or = 0.3). CONCLUSION: In this RA cohort, the MetSyn features of hypertension, insulin resistance, and triglycerides were risk factors for subclinical atherosclerosis, independent of previously identified determinants of cardiovascular disease. Individual MetSyn features were more strongly associated with subclinical atherosclerosis than were currently recommended MetSyn definitions.
18930662 Tumor necrosis factor (TNF) inhibitor therapy for rheumatoid arthritis. 2008 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by inflammation involving large and small joints. Systemic manifestations as well as involvement of paraoral tissues contribute to morbidity. Tumor necrosis factor (TNF) plays a central role in RA by amplifying inflammation in multiple pathways that lead to joint destruction. Tumor necrosis factor inhibitors were first licensed for clinical use in 1998; 3 have been approved for the treatment of RA: Iinfliximab, etanercept, and adalimumab. The purpose of this paper is to review the pathogenesis of RA, the state of the art of therapy, and the most current information on the safety and efficacy of TNF inhibitors for treatment of RA.
18001463 Ultrasonography, magnetic resonance imaging, radiography, and clinical assessment of infla 2007 The aim of the present study was to assess ultrasonography (US) for the detection of inflammatory and destructive changes in finger and toe joints, tendons, and entheses in patients with psoriasis-associated arthritis (PsA) by comparison with magnetic resonance imaging (MRI), projection radiography (x-ray), and clinical findings. Fifteen patients with PsA, 5 with rheumatoid arthritis (RA), and 5 healthy control persons were examined by means of US, contrast-enhanced MRI, x-ray, and clinical assessment. Each joint of the 2nd-5th finger (metacarpophalangeal joints, proximal interphalangeal [PIP] joints, and distal interphalangeal [DIP] joints) and 1st-5th metatarsophalangeal joints of both hands and feet were assessed with US for the presence of synovitis, bone erosions, bone proliferations, and capsular/extracapsular power Doppler signal (only in the PIP joints). The 2nd-5th flexor and extensor tendons of the fingers were assessed for the presence of insertional changes and tenosynovitis. One hand was assessed by means of MRI for the aforementioned changes. X-rays of both hands and feet were assessed for bone erosions and proliferations. US was repeated in 8 persons by another ultrasonographer. US and MRI were more sensitive to inflammatory and destructive changes than x-ray and clinical examination, and US showed a good interobserver agreement for bone changes (median 96% absolute agreement) and lower interobserver agreement for inflammatory changes (median 92% absolute agreement). A high absolute agreement (85% to 100%) for all destructive changes and a more moderate absolute agreement (73% to 100%) for the inflammatory pathologies were found between US and MRI. US detected a higher frequency of DIP joint changes in the PsA patients compared with RA patients. In particular, bone changes were found exclusively in PsA DIP joints. Furthermore, bone proliferations were more common and tenosynovitis was less frequent in PsA than RA. For other pathologies, no disease-specific pattern was observed. US and MRI have major potential for improved examination of joints, tendons, and entheses in fingers and toes of patients with PsA.
18055470 The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretre 2008 Aug OBJECTIVE: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFalpha expression in the synovium before initiation of treatment. METHODS: Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as the expression of various cytokines, adhesion molecules and growth factors. Stained sections were evaluated by digital image analysis. Student t tests were used to compare responders (decrease in DAS28 > or =1.2) with non-responders (decrease in DAS28 <1.2) and multivariable regression was used to identify the independent predictors of clinical response. RESULTS: Synovial tissue analysis confirmed our hypothesis that the baseline level of TNFalpha expression is a significant predictor of response to TNFalpha blocking therapy. TNFalpha expression in the intimal lining layer and synovial sublining were significantly higher in responders than in non-responders (p = 0.047 and p = 0.008, respectively). The numbers of macrophages, macrophage subsets and T cells (all able to produce TNFalpha) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1beta, IL6, IL18, IL10, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was not associated with response to anti-TNFalpha treatment. CONCLUSION: The effects of TNFalpha blockade are in part dependent on synovial TNFalpha expression and infiltration by TNFalpha producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanisms.