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ID PMID Title PublicationDate abstract
19837054 Ten years of infliximab (remicade) in clinical practice: the story from bench to bedside. 2009 Nov 25 Infliximab was first introduced in Europe in 1999 for Crohn's disease. During the following decade major progress was made in the understanding of the pathophysiology of inflammatory bowel diseases and treatment with infliximab. Today, treatment algorithms with anti-TNF and optimization of anti-TNF use in daily clinical practice are important research topics in Crohn's disease and ulcerative colitis. TNF blockade has also changed the rheumatology practice during the last 10 years. Earlier treatment, combination with disease modifying anti-rheumatic drugs, and identification of risk factors of poor prognosis are hot research topics today. The introduction of infliximab (among other biological therapies) has thus changed the way how inflammatory bowel diseases and rheumatoid conditions are treated. More importantly, infliximab has offered significant improvement of the quality of life of many patients. In addition, we currently collect data indicating that infliximab is changing the natural course of these inflammatory diseases.
19796530 Association of salivary S. mutans colonisation and mannose-binding lectin deficiency with 2009 Mar OBJECTIVE: The present study aimed to investigate the interactions among salivary S. mutans colonisation, serum mannose binding lectin level (MBL), oral ulcer activity and disease course in patients with Behçet's disease (BD). METHODS: One hundred and six BD patients, 25 patients with rheumatoid arthritis (RA) and 42 healthy controls (HC) were included in the study. BD patients were grouped as active (n=52) or inactive (n=54) according to oral ulcer status of the previous 3 months. Salivary colonisation of S. mutans levels were investigated by standard Caries Risk Test (CRT) Bacteria kits (Ivoclar, Vivadent). S. mutans colonies were categorized as high (> or =10(5) colony forming unit (CFU)/ml of saliva) or low (10(5)CFU/ml). Serum mannose binding lectin (MBL) levels were measured by ELISA. RESULTS: High levels of salivary S. mutans colonisation was significantly more present in BD (50%) than HC (28.6%)(p=0.039), whereas no significant difference was observed between RA and other groups (p>0.05). S. mutans presence in saliva was associated with oral ulcers (61.5% in patients with active oral ulcers vs 38.9% in inactives) (p=0.020). S. mutans colonisation in saliva was significantly higher among male BD patients with a severe disease course than a milder disease (p=0.04). Increased salivary S. mutans colonisation was also related to very low serum MBL (<100 ng/ml) in BD compared to controls (p=0.04). CONCLUSION: The relationship between increased presence of S. mutans and MBL deficiency with active disease pattern may indicate an impaired innate immune response in BD patients which may predispose to oral infections and a severe disease course.
20509981 Fish oil and rheumatoid arthritis: past, present and future. 2010 Aug Meta- and mega-analysis of randomised controlled trials indicate reduction in tender joint counts and decreased use of non-steroidal anti-inflammatory drugs with fish-oil supplementation in long-standing rheumatoid arthritis (RA). Since non-steroidal anti-inflammatory drugs confer cardiovascular risk and there is increased cardiovascular mortality in RA, an additional benefit of fish oil in RA may be reduced cardiovascular risk via direct mechanisms and decreased non-steroidal anti-inflammatory drug use. Potential mechanisms for anti-inflammatory effects of fish oil include inhibition of inflammatory mediators (eicosanoids and cytokines), and provision of substrates for synthesis of lipid suppressors of inflammation (resolvins). Future studies need progress in clinical trial design and need to shift from long-standing disease to examination of recent-onset RA. We are addressing these issues in a current randomised controlled trial of fish oil in recent-onset RA, where the aim is to intervene before joint damage has occurred. Unlike previous studies, the trial occurs on a background of drug regimens determined by an algorithm that is responsive to disease activity and drug intolerance. This allows drug use to be an outcome measure whereas in previous trial designs, clinical need to alter drug use was a 'problem'. Despite evidence for efficacy and plausible biological mechanisms, the limited clinical use of fish oil indicates there are barriers to its use. These probably include the pharmaceutical dominance of RA therapies and the perception that fish oil has relatively modest effects. However, when collateral benefits of fish oil are included within efficacy, the argument for its adjunctive use in RA is strong.
20078616 Is there an anti-inflammatory effect of statins in rheumatoid arthritis? Analysis of a lar 2010 Jan WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * The increasing evidence of the anti-inflammatory action of statins has stimulated interest in whether these might be beneficial in disease management of rheumatoid arthritis (RA), a chronic diseases characterized by high levels of inflammation. * The TARA trial (McCarey 2004) suggested a significant reduction in disease activity outcomes in RA patients randomized to atorvastatin compared with those assigned to the placebo harm. * However, as the signal reported by the trial was small, more evidence is needed. WHAT THIS PAPER ADDS: * We investigated the possible anti-inflammatory effect of statins in a cohort of RA patients using a large health insurance claims database. * To our knowledge, this is the largest study ever conducted on the anti-inflammatory effects of statins. * Our data do not show any beneficial effect of statins in reducing disease inflammation in RA patients. AIM: To investigate the possible anti-inflammatory effect of statins in a cohort of rheumatoid arthritis (RA) patients. METHODS: We conducted a cohort study consisting of all patients with at least one claim for RA using LifeLink, a health insurance claims database. Initiation and cessation of oral steroid (OS) therapy were treated as surrogate for inflammatory flare-up and controlled inflammation, respectively. We split the RA patients into two sub-cohorts based on whether they were using OS within a specified time window of the RA index date (first recorded claim for RA in the database). Cox proportional hazard models were used to evaluate the association between time-varying exposure to any statins and (i) initiation of OS therapy in the non-users of OS at RA index date and (ii) cessation of OS therapy in the users of OS at RA index date controlling for potential confounders. RESULTS: We found 31 451 non-users of OS at RA index date and 6026 users of OS within the time window at RA index date. The results on both sub-cohorts were both consistent with no association of statin exposure with the risk of initiation/cessation of OS: the hazard ratio (HR) of initiating OS therapy was 0.96 (95% confidence interval 0.9, 1.01) in the sub-cohort of non-users and the HR of cessation of OS therapy was 0.95 (0.87, 1.05) in the sub-cohort of users of OS therapy at RA diagnosis. CONCLUSIONS: These data do not show any beneficial effect of statins in reducing disease inflammation in RA patients.
19445880 [Methotrexate-associated lymphoproliferative disorder presenting as oral ulcers in a patie 2009 Mar Methotrexate-associated lymphoproliferative disorders are a heterogeneous group of lymphoid proliferations or lymphomas that develop in patients with autoimmune diseases treated using methotrexate. These lymphoproliferative disorders are often associated with Epstein-Barr virus infection and occasionally regress after the withdrawal of methotrexate therapy. The lymphoproliferative disorder in this case was diffuse large B-cell lymphoma, unusually presenting as oral ulcers in a 79-year-old woman on treatment with methotrexate for longstanding rheumatoid arthritis. Latent membrane protein 1 positivity was detected by immunohistochemistry and Epstein-Barr-virus encoded small RNA positivity by chromogenic in situ hybridization. Clonality was confirmed by immunohistochemistry (kappa light-chain restriction), polymerase chain reaction (monoclonal immunoglobulin H gene rearrangement), and capillary electrophoresis (GeneScan). Staging procedures were negative. Withdrawal of methotrexate therapy led to complete remission within 6 weeks, and the patient is alive and disease-free 18 months after the diagnosis was made. The oral cavity is not often involved in the initial presentation of methotrexate-associated lymphoproliferative disorders, and presentation with intraoral ulcers is very rare. We have performed a review of the literature on methotrexate-associated lymphoproliferative disorders presenting as ulcers in the oral cavity.
21073728 Novel method of monitoring trace cytokines and activated STAT molecules in the paws of art 2010 Nov 12 BACKGROUND: The use of mouse models to study human disease provides useful data that can provide support for research projects or an existing drug discovery program. How well a model recapitulates the human condition and the ease and reproducibility of data collected will determine how much confidence a scientist can place on results obtained. Designing new treatments for rheumatic diseases, such as rheumatoid arthritis (RA), requires complex immunocompetent models that depend on intricate cytokine networks. Using local cytokines, signal transduction and transcription factor molecules as potential biomarkers to monitor disease and treatment efficacy is the best method to follow the progression of tissue damage and repair when testing an unknown compound or biologic. Described here in this report, a novel method for the non-enzymatic extraction and measurement of cytokines and signal transducers and activators of transcription (STAT) molecules using Luminex® bead array technology in two different mouse models for human RA--collagen antibody-dependent arthritis (CAIA) and collagen-induced arthritis (CIA). RESULTS: Dynamic expression of several pro-inflammatory cytokines responsible for promoting disease augmentation overtime were monitored, such as IL-1β, TNFα, IL-6 and IL-12, locally in the paws of affected animals directly ex vivo. Local cytokine responses could be matched with serum cytokine levels and joint pathology results. In addition, STAT1, 3, and 5a/b activation status could be monitored with confidence using specifically formulated extraction buffer that protected the phosphorylation site. STAT3 activation followed paw swelling and cytokine levels in both models and correlates of disease could be ablated upon treatment with dexamethasone. Here reported a novel method of extracting joint fluid from the paws of inflamed mice coupled with powerful multiplex bead technology allowing us to measure cytokine responses, pharmacodynamic markers such as STATs and pharmacokinetic analysis of dosed agent all from the same sample directly ex vivo. CONCLUSIONS: This method is powerful in that it is applicable to multiple autoimmunity model types, streamlines ex vivo readouts in a high-throughput manner, and allows multiplexing providing the investigator with an array of options and possible analytes when developing preclinical animal models to support drug discovery efforts in the search for new treatments for rheumatic diseases.
19255426 Telomerase insufficiency in rheumatoid arthritis. 2009 Mar 17 In rheumatoid arthritis (RA), chronically stimulated T lymphocytes sustain tissue-destructive joint inflammation. Both naïve and memory T cells in RA are prematurely aged with accelerated loss of telomeres suggesting excessive proliferative pressure or inadequate telomeric maintenance. Upon stimulation, RA naïve CD4 T cells are defective in up-regulating telomerase activity (P < 0.0001) due to insufficient induction of the telomerase component human telomerase reverse transcriptase (hTERT); T cell activation and cell cycle progression are intact. Telomerase insufficiency does not affect memory T cells or CD34 hematopoietic stem cells and is present in untreated patients and independent from disease activity. Knockdown of hTERT in primary human T cells increases apoptotic propensity (P = 0.00005) and limits clonal burst (P = 0.0001) revealing a direct involvement of telomerase in T cell fate decisions. Naïve RA CD4 T cells stimulated through the T cell receptor are highly susceptible to apoptosis, expanding to smaller clonal size. Overexpression of ectopic hTERT in naïve RA T cells conveys apoptotic resistance (P = 0.008) and restores proliferative expansion (P < 0.0001). Telomerase insufficiency in RA results in excessive T cell loss, undermining homeostatic control of the naive T cell compartment and setting the stage for lymphopenia-induced T cell repertoire remodeling. Restoring defective telomerase activity emerges as a therapeutic target in resetting immune abnormalities in RA.
20112385 Association of the response to tumor necrosis factor antagonists with plasma type I interf 2010 Feb OBJECTIVE: Despite the substantial clinical efficacy of tumor necrosis factor alpha (TNFalpha) antagonist therapy in patients with rheumatoid arthritis (RA), some patients respond poorly to such agents. Since an interferon (IFN) signature is variably expressed among RA patients, we investigated whether plasma type I IFN activity might predict the response to TNF antagonist therapy. METHODS: RA patients (n = 35), the majority of whom were Hispanic, from a single center were evaluated before and after initiation of TNF antagonist therapy. As controls, 12 RA patients from the same center who were not treated with a TNF antagonist were studied. Plasma type I IFN activity was measured using a reporter cell assay, and disease status was assessed using the Disease Activity Score in 28 joints (DAS28). Levels of interleukin-1 receptor antagonist (IL-1Ra) were determined in baseline plasma samples using a commercial enzyme-linked immunosorbent assay. The clinical response was classified according to the European League Against Rheumatism criteria for improvement in RA. RESULTS: Plasma type I IFN activity at baseline was significantly associated with clinical response (odds ratio 1.36 [95% confidence interval 1.05-1.76], P = 0.020), with high baseline IFN activity associated with a good response. Changes in DAS28 scores were greater among patients with a baseline plasma IFNbeta/alpha ratio >0.8 (indicating elevated plasma IFNbeta levels). Consistent with the capacity of IFNbeta to induce IL-1Ra, elevated baseline IL-1Ra levels were associated with better therapeutic outcomes (odds ratio 1.82 [95% confidence interval 1.1-3.29], P = 0.027). CONCLUSION: The plasma type I IFN activity, the IFNbeta/alpha ratio, and the IL-1Ra level were predictive of the therapeutic response in TNF antagonist-treated RA patients, indicating that these parameters might define clinically meaningful subgroups of RA patients with distinct responses to therapeutic agents.
19424730 The characteristics of bony ankylosis of the facet joint of the upper cervical spine in rh 2009 Aug This study investigated the bony ankylosis of the upper cervical spine facet joints in patients with a cervical spine involvement due to rheumatoid arthritis (RA) using computed tomography (CT) and then examined the characteristics of the patients showing such ankylosis. Forty-six consecutive patients who underwent surgical treatment for RA involving the cervical spine were reviewed. The radiographic diagnoses included atlanto-axial subluxation in 30 cases, vertical subluxation (VS) in 10 cases, VS + subaxial subluxation in 3 cases and cervical spondylotic myelopathy in 3 cases. The patients were classified into two groups, those developing bony ankylosis or not and then the differences in the patient characteristics between the two groups was investigated. Furthermore, cervical spine disorders and surgeries were also evaluated in patients who demonstrated such bony ankylosis. The CT reconstruction image demonstrated bony ankylosis in 12 patients (group BA), and the remaining 34 cases (group NB) showed no bony ankylosis. The level at which bony ankylosis occurred was atlanto-occipital joint (AOJ) in eight cases, atlanto-axial joint (AAJ) in two cases and AOJ, AAJ in two cases. No differences were observed between the two groups (age P > 0.54, gender P > 0.39, duration of RA P > 0.72). There was a significant difference between two groups in the patients showing obvious neurological impairment (P = 0.017). In BA group, arthrodesis or decompression was adapted for a caudal region of bony ankylosis. In conclusion, bony ankylosis of the facet joint of the upper cervical spine was detected in 12 of 46 RA patients with involvement of the cervical spine who thus required surgery. These findings showed that the patients demonstrating such ankylosis showed severe cervical myelopathy. In addition, we suggest that the occurrence of bony ankylosis was a risk factor for instability of AAJ, and subaxial instability or stenosis.
19359106 Reconstruction of the extensor central slip using a distally based flexor digitorum superf 2009 May Several methods have been reported for reconstruction of the extensor central slip. We describe the successful use of a distally based slip of the flexor digitorum superficialis tendon for the reconstruction of an incompetent central slip of the extensor mechanism. The flexor digitorum superficialis tendon was transferred from volar to dorsal through the base of the middle phalanx and then woven through the extensor tendon over the proximal phalanx. The technique is straightforward and appears to be robust.
19714586 Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-in 2009 Sep OBJECTIVE: To evaluate the expression and functional ability of the high-affinity interleukin-7 receptor (IL-7Ralpha) in patients with rheumatoid arthritis (RA). METHODS: Expression of IL-7Ralpha and IL-7 was determined in synovial tissue from RA patients and was compared with that in synovial tissue from patients with undifferentiated arthritis (UA) and osteoarthritis (OA). IL-7Ralpha expression on CD4 T cells, CD19 B cells, and CD14 monocyte/macrophages from RA synovial tissue, synovial fluid, and peripheral blood was also assessed. The proliferative capacity of IL-7Ralpha(bright) and IL-7Ralpha(dim/-) T cells was measured. In addition, we examined IL-7R blockade with soluble human IL-7Ralpha (hIL-7Ralpha) in the prevention of immune activation of peripheral blood mononuclear cells. RESULTS: We found significantly higher IL-7Ralpha expression in RA and UA synovial tissue than in OA synovial tissue, and the level of IL-7Ralpha expression correlated significantly with the levels of CD3 and IL-7 expression. CD4 T cells from RA synovial fluid and synovial tissue strongly expressed IL-7Ralpha. A substantial percentage of B cells and macrophages from RA synovial fluid and synovial tissue also expressed IL-7Ralpha, although less prominently than T cells. We found that peripheral blood IL-7Ralpha(bright) T cells that did not express FoxP3 were highly proliferative as compared with IL-7Ralpha(dim/-) T cells that did express high levels of FoxP3. Soluble hIL-7Ralpha inhibited IL-7-induced proliferation and interferon-gamma production by mononuclear cells from RA patients. CONCLUSION: Our data suggest that enhanced expression of IL-7Ralpha and IL-7 in RA patients contributes significantly to the joint inflammation by activating T cells, B cells, and macrophages. The inhibition of IL-7R-mediated immune activation by soluble hIL-7Ralpha further indicates an important role of IL-7Ralpha in inflammatory responses in RA, suggesting IL-7Ralpha as a therapeutic target for immunotherapy in RA.
20406613 Psychometric properties of an index of three patient reported outcome (PRO) measures, term 2010 Mar OBJECTIVES: To evaluate the psychometric properties of an index based on 3 patient reported outcomes measures, termed PRO-CLinical ARthritis Activity (PRO-CLARA), in order to facilitate rapid and easy rheumatoid arthritis (RA) activity assessment in daily routine. METHODS: 196 patients partially or not responding to disease modifying anti-rheumatic drugs (DMARDs), consented to participate in a multicentre cross-sectional study. For the evaluation of the psychometric properties of the PRO-CLARA, this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study and who satisfying minimal disease activity and remission definitions. All patients completed the PRO-CLARA, combining patient's physical function, self-administered tender joint count and perception of global health status into a single measure of disease activity. Additional comparator composite indices were analysed. Internal consistency was assessed with Cronbach's alpha coefficient. A confirmatory factor analysis was carried out to test factor structure. Concurrent validity was analyzed using Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis, kappa statistics were calculated. RESULTS: In testing for internal consistency, we found that Cronbach's alpha for the PRO-CLARA was 0.893, indicating high reliability. PRO-CLARA proved to be significantly correlated to established RA activity assessment tools. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator indices. CONCLUSIONS: The study showed satisfactory psychometric properties of the PRO-CLARA.
20398020 Early disease control by low-dose prednisone comedication may affect the quality of remiss 2010 Apr In order to identify rate and stability of remission induced by low-dose prednisone comedication in early rheumatoid arthritis (RA), we evaluated patients with early RA (<1 year) who were randomized to receive (P) or not (non-P) low-dose prednisone in association with step-up disease-modifying antirheumatic drug therapy over 2 years. Prevalence and duration of clinical remission were evaluated in the first and second year. Each treatment group included 105 patients; no significant differences were found at baseline. During the first year, P patients achieved higher rates of clinical remission with a time-averaged odds ratio (OR) of 1.965 (CI 95% 1.214-3.182, P= 0.006). Moreover, they showed a higher probability of sustained remission during the second year (OR 4.480, CI 95% 1.354-14.817, P= 0.014). In conclusion, we found as in early RA low-dose prednisone comedication is associated with higher rate of clinical remission, earlier disease activity control and more stable remission over time.
20065639 Golimumab. 2009 Sep Golimumab, a human anti-TNFalpha IgG1kappa monoclonal antibody, was approved in the US and Canada in April 2009 as a treatment for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and is undergoing regulatory review in the EU for these indications. The product was developed by Centocor and Janssen Pharmaceutical KK (Johnson & Johnson subsidiaries), in collaboration with Schering-Plough and Mitsubishi Tanabe Pharma. Golimumab faces numerous protein therapeutic competitors on the market, but, as the first patient-administered, once-monthly dosed anti-TNFalpha drug, it will likely be an attractive option for patients.
20223054 Temporal trends in primary total hip and knee arthroplasty surgery: results from a UK regi 2010 Apr INTRODUCTION: The aim of this study was to evaluate temporal trends in the prevalence of primary total hip and knee replacements (THRs and TKRs) throughout the Trent region from 1991 to 2004. PATIENTS AND METHODS: The Trent Regional Arthroplasty Study records details of primary THR and TKR prospectively and data from the register were examined. Age and gender population data were provided by the Office for National Statistics. RESULTS: A total of 26,281 THRs and 23,606 TKRs were recorded during this period. Analysis showed that females had an increased incidence rate ratio (IRR) for both primary THR (IRR = 1.29; 95% CI 1.26-1.33; P < 0.001) and TKR (IRR = 1.17; 95% CI 1.14-1.20; P < 0.001). Patients aged 74-85 years had the largest IRR for both primary THR (IRR = 6.7; 95% CI 6.4-7.0; P < 0.001) and TKR (IRR = 15.3; 95% CI 14.4-16.3; P < 0.001). CONCLUSIONS: The prevalence of primary TKR increased significantly over time whereas THR remained steady in the Trent region between 1991 and 2004.
20495735 Matrix metalloproteinases involvement in pathologic conditions. 2010 Matrix metalloproteinases (MMPs) have a great variability that provides a complex intervention in pathophysiological conditions. MMPs roles in pathology may be grouped into the following main types: (1) tissue destruction, as in cancer invasion and metastasis, rheumatoid arthritis, osteoarthritis, different types of ulcers, periodontal disease, brain injury and neuroinflammatory diseases; (2) fibrosis, as in liver cirrhosis, fibrotic lung disease, otosclerosis, atherosclerosis, and multiple sclerosis; (3) weakening of matrix, as in dilated cardiomyopathy, epidermolysis bullosa, aortic aneurysm and restenotic lesions. Recent data also adds new MMPs functions in angiogenesis and apoptosis. Interesting opposite intervention in escaping mechanisms vs. antitumor defensive mechanisms had been also reported. As MMP-7 is expressed by tumor cells of epithelial and mesenchymal origin, it may be used as a biological marker of an aggressive phenotype and as a target of therapeutic intervention. MMPs play a pivotal role in the pathogenesis of arthritis, atherosclerosis, pulmonary emphysema, and endometriosis. Although MMP involvement in pathology is more than simple excessive matrix degradation, or an imbalance between them and their specific tissular inhibitors (TIMPs), MMP inhibition may be of therapeutic benefit, so synthetic MMPs inhibitors had been developed and are currently under clinical testing.
21044441 Folate supplementation during methotrexate therapy for rheumatoid arthritis. 2010 Sep Methotrexate (MTX), an antifolate, is an anchor drug for the treatment of rheumatoid arthritis (RA). Both folic acid (FA) and folinic acid (FLN) supplements have been shown to reduce the toxicity of MTX when used in RA therapy. The effect of folate supplementation on MTX efficacy still needs to be studied. FA supplementation has been found to have a beneficial effect on homocysteine (hcy) metabolism and may prevent the formation of the less effective metabolite 7-hydroxy-MTX. The cost of FA supplements is substantially less than the cost of FLN supplements. This article reviews clinical trials related to folate supplementation during MTX therapy for RA.
19252251 [Benefits and risks of glucocorticoid therapy for the treatment of rheumatoid arthritis an 2009 Mar More than 50 years have passed since glucocorticoid (GC) therapy was introduced into the treatment of rheumatoid arthritis (RA) . Although the effect of GC monotherapy on RA is limited to short-term and long-term GC treatment carries the risks of adverse effects and rebound phenomenon after the discontinuation, disease-modifying action of GC have been recently reported when used in combination with DMARDs. One of the important side effects associated with GC therapy is osteoporosis, and Japanese guidelines on the management and treatment of glucocorticoid -induced osteoporosis have been published recently. Further studies are necessary to elucidate long-term benefit-risk ratio of low-dose GC therapy on RA.
20448286 Association between anti-tumour necrosis factor treatment response and genetic variants wi 2010 Jul OBJECTIVE: To determine whether genetic variation within genes integral to the Toll-like receptor (TLR) and NFkappaB signalling systems, two cardinal regulators of inflammatory and immune responses, contributes towards the observed variation in response to tumour necrosis factor (TNF) blocking agents in patients with rheumatoid arthritis (RA). METHODS: Pairwise-tagging single nucleotide polymorphisms (SNPs) spanning 24 candidate genes were selected and genotyped in a large UK cohort of patients receiving anti-TNF therapy for RA. Multivariate regression analyses were performed to test association between individual genotypes, under an additive model, and treatment response at 6 months' follow-up assessed using both the absolute change in 28-joint count Disease Activity Score (DAS28) and the European League Against Rheumatism (EULAR) response criteria. Analyses were performed across subgroups comprising etanercept-, infliximab- and infliximab/adalimumab-treated patients as well as the combined anti-TNF-treated cohort. p Values <0.05 were considered statistically significant. RESULTS: A total of 187 SNPs were successfully genotyped and analysed in 909 patients. Eight SNPs spanning six genes demonstrated nominal evidence of association with response (DAS28) across the anti-TNF-treated subgroups, six of which were restricted to etanercept-treated patients. Twelve SNPs spanning nine genes demonstrated nominal evidence of association with treatment response (DAS28 and/or EULAR) across the combined anti-TNF cohort. These included SNPs mapping to MyD88 (rs7744) and CHUK (rs11591741), which were associated under each model applied (etanercept-treated and combined anti-TNF cohort analysis (DAS28 and EULAR)). CONCLUSIONS: Several SNPs mapping to the TLR and NFkappaB signalling systems demonstrated association with anti-TNF response as a whole and, in particular, with response to etanercept. Validation of these findings in an independent cohort is now warranted.
21051173 Unmet information needs about the delivery of rheumatology health care services: a survey 2011 Nov OBJECTIVE: To measure patient-perceived knowledge and information need regarding regional health care services and their determinants among 400 patients with rheumatoid arthritis (RA) and to identify the preferred method of information provision. METHODS: Postal survey on knowledge and information need (content and accessibility) of 18 regional health care services and preferences for the mode of delivery of information. Logistic regression analyses determined which factors were associated with insufficient knowledge and information need. RESULTS: Two-hundred and thirty-seven (94%) patients reported insufficient knowledge about the contents and 235 (94%) about the accessibility of at least one health care services, whereas 172 patients (69%) reported an information need about the content and 154 (61%) on the accessibility. Age was significantly associated with knowledge whereas both age and physical functioning were significantly associated with information need. Seventy-nine percent of the patients mentioned written information, 21% the Internet and 12% personal contact with a professional as a preferred method of information delivery. CONCLUSION: Many RA patients reported a lack of knowledge or information need concerning the contents and accessibility of regional health care services. PRACTICE IMPLICATIONS: Active strategies to provide practical information about health care services are needed for RA patients.