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ID PMID Title PublicationDate abstract
19373479 Mid-term outcome of GSB-III total elbow arthroplasty in patients with rheumatoid arthritis 2009 Nov INTRODUCTION: We reviewed the mid-term outcome of GSB-III semi-constrained total elbow arthroplasty (TEA) and compared the results of patients with rheumatoid arthritis (RA) and those suffering from post-traumatic arthritis (PTA). PATIENTS: Forty-five patients with 54 replaced elbows, with an average age of 69 (range 49-84) were clinically [using Mayo Clinical Performance Index (MCPI) and Liverpool Elbow Score (LES)] and radiographically assessed. The average follow-up was 54 (range 20-103) months. RESULTS: Based on MCPI 82% of patients had excellent or good outcome. This figure was 88% for RA and 64% for PTA group (P = 0.22). Overall MCPI was 83.7(+/- 19) and LES 7.5 (+/- 1.8). Neither the MCPI (P = 0.39) nor the LES (P = 0.95) were statistically different between the RA and PTA groups. The mid-term outcome of GSB-III TEA is satisfactory. CONCLUSION: The recommendation of TEA, including in patients with PTA, is supported.
19473335 Why do patients with inflammatory arthritis often score states "worse than death" on the E 2009 Sep OBJECTIVE: Using inflammatory arthritis patients as an example, we investigate EuroQol-5D (EQ-5D) profiles resulting in states worse than death (WTD), and the heath status of patients occupying these states. METHODS: Baseline data from two UK trials were used that reflected the range of arthritis states/severity found in routine practice. EQ-5D profiles resulting in negative valuations (i.e., states WTD) based on UK weights were identified. EQ-5D scores for these profiles from alternative valuation sets, including a reanalysis of the UK weights, were compared. The health status and characteristics of patients, and factors associated with patients in the low distribution of the EQ-5D and those with WTD EQ-5D scores were identified. RESULTS: Seven hundred patients were included in the analysis. Sixty-two (9%) patients occupied states WTD. Patients occupied 9 of the possible 84 health profiles with negative scores (53% occupied one profile); this profile was not rated WTD by any of the alternative EQ-5D scoring algorithms. All WTD profiles included severe pain/discomfort plus moderate problems in >or=3 other domains. Patients with WTD valuations reported higher levels of pain, and feeling downhearted and low on alternative health status measures. CONCLUSIONS: Pain was the predominant factor in the WTD EQ-5D profiles occupied by arthritis patients. Patients occupying states WTD have poorer health-related quality of life than patients in low "better than death" states. Valuations of profiles vary according to how sets of preference weights for health profiles were developed. Further research should explore whether WTD valuations are supported by qualitative evidence and reflect the patient's health and experience of disease.
20511609 Role of the cholinergic nervous system in rheumatoid arthritis: aggravation of arthritis i 2010 Sep BACKGROUND: The alpha7 subunit of nicotinic acetylcholine receptors (alpha7nAChR) can negatively regulate the synthesis and release of proinflammatory cytokines by macrophages and fibroblast-like synoviocytes in vitro. In addition, stimulation of the alpha7nAChR can reduce the severity of arthritis in murine collagen-induced arthritis (CIA). OBJECTIVE: To provide more insight into the role of the alpha7nAChR in the pathogenesis of arthritis by investigating the effect of the absence of alpha7nAChR in CIA in alpha7-deficient (alpha7nAChR(-/-)) compared with wild-type (WT) mice. METHODS: CIA was induced in alpha7nAChR(-/-) and WT littermate mice at day 0 by immunisation with chicken collagen type II (cCII) followed by a booster injection with cCII on day 20. Mice were killed on day 44 or day 63 and arthritis activity as well as radiological and histological damage were scored. The effects on the immune response were evaluated by measurement of antigen-specific antibodies and cytokines, and evaluation of the effects on antigen-specific stimulated spleen cells. RESULTS: In alpha7nAChR(-/-) mice a significant increase in the incidence and severity of arthritis as well as increased synovial inflammation and joint destruction were seen. Exacerbation of CIA was associated with elevated systemic proinflammatory cytokines and enhanced T-helper cell 1 (Th1)-cytokine and tumour necrosis factor alpha production by spleen cells. Moreover, a specific decrease in the collagen-specific 'Th1-associated' IgG2a response was seen, whereas IgG1 titres were unaffected. CONCLUSIONS: The results presented here indicate that immune cell function in a model of rheumatoid arthritis is regulated by the cholinergic system and, at least in part, mediated by the alpha7nAChR.
20020313 Cryotherapy decreases histamine levels in the blood of patients with rheumatoid arthritis. 2010 Mar INTRODUCTION: Conventional physiotherapy (electrotherapy, magnetic fields), kinesitherapy, and whole-body cryotherapy (plus kinesitherapy) are used to relieve pain and inflammation or to improve function in rheumatic diseases. The aim of this study was to investigate the effects of different physiotherapies and cryotherapy on biochemical blood parameters of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). MATERIALS AND METHODS: Twenty patients with RA and 17 patients with OA received whole-body cryotherapy at -140 to -160 degrees C for 2 to 3 min, once daily for 4 weeks. The second group of patients (24 with RA and 28 with OA) received conventional physiotherapy for 4 weeks. We measured the parameters of neutrophil activation (respiratory burst, calprotectin) and markers of cartilage metabolism [N-acetyl-beta-D-hexosaminidase (NAHase), ectonucleotide pyrophosphohydrolase (NTPPHase)] twice: before and 3 months after cryotherapy or physiotherapy. RESULTS: We showed, for the first time, that cryotherapy significantly reduced (P < 0.001) histamine levels in the blood of patients with RA. The effect was long-lasting (for at least 3 months). The levels of blood histamine in patients with OA were not changed significantly. Cryotherapy also downregulated the respiratory burst of PMNs and NAHase activity and upregulated calprotectin levels and the activity of NTPPHase. However, these changes were not statistically significant. In contrast, there were no significant changes in histamine levels or the other biochemical parameters measured in groups of patients treated only with physiotherapy and kinesitherapy. CONCLUSION: It may be concluded that the beneficial clinical effects of cryotherapy in RA patients are in part due to the action on the production, release, or degradation of histamine.
19917160 Obstacle avoidance in persons with rheumatoid arthritis walking on a treadmill. 2009 Sep OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of falling. In healthy elderly persons with a history of falling, a reduced ability to avoid obstacles while walking has been shown to relate to increased fall risk. The aim of this study was to determine whether this potential risk factor for falls would also be present in persons with RA. METHODS: Twelve RA patients and twelve controls performed an obstacle avoidance task on a treadmill. The obstacle was released during three different phases of the gait cycle (late stance, early swing and mid swing) to create increasing difficulty levels. The primary outcome measure was failure rate. RESULTS: Overall, the RA patients had significantly higher obstacle avoidance failure rates. To avoid an obstacle, a long or a short stride strategy can be used, the choice of which depends on the phase of obstacle release. There were no significant group differences in the distribution of obstacle avoidance strategies. However, the RA patients made significantly more failures when performing a short stride strategy in mid swing obstacle release trials (the condition which gave the patients the least time to react; available response time). In addition, compared to the controls, the RA group approached the obstacle more closely prior to obstacle crossing (shorter toe distance), thereby increasing the risk of stumbling. CONCLUSION: Obstacle avoidance performance in persons with RA is significantly deteriorated compared to age- and gender-matched controls, especially when available response time is low. This deficit may contribute to their higher fall risk.
20191119 CD20cy and CD45RO immunoexpression in early rheumatoid arthritis synovium. 2010 In this paper, we studied 15 cases of early rheumatoid arthritis presenting with inflammatory lesions in different degrees of evolution. We want to highlight B- and T-lymphocytes in synovial tissue collected from patients diagnosed with early rheumatoid arthritis, to establish the pattern of their distribution, possibly in relation to local neovascularisation to determine the role played by these types of cells. The pathological samples were represented by synovial membrane biopsy fragments, which were examined by histopathological and immunohistochemical methods. We noticed a perivascular distribution of lymphocyte infiltrate, up to formation of lymphoid follicles with germinal centers. There is a close interdependence between B- and T-lymphocytes in these lesions, and their presence in the synovial membrane in relation to newly formed blood vessels facilitates their action and their chemical mediators. Studying the interdependence of different types of lymphocytes and their connection with blood vessels may generate new therapeutic targets.
20683739 Treating early rheumatoid arthritis intensively: current UK practice does not reflect guid 2011 Jan Recent guidance published in the UK by the National Institute for Health and Clinical Excellence has recommended that patients with early rheumatoid arthritis (RA) are treated with combination disease-modifying anti-rheumatic drugs (DMARDs). It is unclear to what extent this reflects current UK practice. UK rheumatologists were asked to complete a web-based questionnaire asking about their treatment preferences in early RA and to indicate their attitudes to combination DMARD therapy. Although the majority was using step-up combination DMARDs, only 50% of the 258 respondents were using initial combination therapy in any patients with newly diagnosed RA despite scoring it highly for efficacy and safety. Concerns were expressed about side effects, increased monitoring requirements, and acceptability to patients. Current UK practice does not reflect the recently published guidelines. Uncertainties remain as to which patients need combination therapy and the optimal regimes to use. Further research is required to elucidate attitudes to aggressive therapy in early disease.
19686927 Endogenous glutamate in association with inflammatory and hormonal factors modulates bone 2009 Sep PURPOSE: The aim of this study was to investigate the relation between plasma level of glutamate and extent of radiographic bone erosion of the temporomandibular joint (TMJ) in patients with early rheumatoid arthritis (RA) in relation to inflammatory disease activity as well as estradiol and testosterone. MATERIALS AND METHODS: A total of 47 patients (29 women and 18 men) of whom 24 were seropositive were included shortly after being diagnosed with RA. Radiographic signs of bone tissue resorption (erosions) in the TMJ were recorded by cone-beam CT images, and an erosion score (0 to 24) was calculated for each patient. Venous blood was analyzed for rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, leukocyte particle count, glutamate, estradiol, and testosterone. Nonparametric statistical methods were used in the analysis. RESULTS: Resorptive changes of the TMJ were found in a major part of the patients. There was a significant positive correlation between plasma level of glutamate and extension of radiographic erosions that was strongest in the patients with low levels of C-reactive protein, estradiol, or testosterone. By contrast, erosions were correlated with C-reactive protein in patients with high levels of estradiol. The highest levels of glutamate were found in patients with low levels of C-reactive protein and estradiol. CONCLUSIONS: This study shows that a majority of patients with early RA presents radiographic signs of bone tissue resorption of the TMJ and that circulating glutamate is associated with the extent of these changes. The relationship between glutamate and bone resorption seems to be influenced by systemic inflammatory activity as well as estradiol and testosterone levels.
20444750 EULAR recommendations for the management of rheumatoid arthritis with synthetic and biolog 2010 Jun Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.
18375541 Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not 2009 Jan OBJECTIVE: To determine whether rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, or carriage of shared epitope (SE) and PTPN22 genetic susceptibility variants predict response to therapy in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) agents. METHODS: UK-wide multicentre collaborations were established to recruit a large cohort of patients treated with anti-TNF drugs for RA. Serum RF, anti-CCP antibody and SE status were determined using commercially available kits. PTPN22 R620W genotyping was performed by Sequenom MassArray. Linear regression analyses were performed to investigate the role of these four factors in predicting response to treatment by 6 months, defined as the absolute change in 28-joint Disease Activity Score (DAS28). RESULTS: Of the 642 patients analysed, 46% received infliximab, 43% etanercept and 11% adalimumab. In all, 89% and 82% of patients were RF and anti-CCP positive, respectively. Patients that were RF negative had a 0.48 (95% CI 0.08 to 0.87) greater mean improvement in DAS28 compared to patients that were RF positive. A better response was also seen among patients that were anti-CCP negative. No association was demonstrated between drug response and SE or PTPN22 620W carriage. CONCLUSION: The presence of RF or anti-CCP antibodies was associated with a reduced response to anti-TNF drugs. However, these antibodies only account for a small proportion of the variance in treatment response. It is likely that genetic factors will contribute to treatment response, but these do not include the well established RA susceptibility loci, SE and PTPN22.
20506350 SIGIRR/TIR-8 is an inhibitor of Toll-like receptor signaling in primary human cells and re 2010 Aug OBJECTIVE: Single-immunoglobulin interleukin-1 receptor-related (SIGIRR), which is also known as Toll/interleukin-1 receptor 8 (TIR-8), is a member of the TIR domain-containing family of receptors and was first characterized as an inhibitor of interleukin-1 receptor (IL-1R) and Toll-like receptor (TLR) signaling. In the Dextran sulfate sodium-induced colitis model, SIGIRR(-/-) mice were shown to have increased inflammation and to be more susceptible to endotoxin challenge. Increasing evidence implicates TLR and IL-1R signaling in the pathology of rheumatoid arthritis (RA). Therefore, the purpose of this study was to investigate the involvement of SIGIRR in regulating inflammation in disease-relevant models. METHODS: Primary human monocyte-derived macrophages and dendritic cells (DCs) were used to overexpress SIGIRR as well as to knock down endogenously expressed SIGIRR using small interfering RNAs. SIGIRR was also overexpressed in synovial cells derived from RA patients. To investigate the role of SIGIRR in vivo, zymosan-induced arthritis (ZIA) and collagen antibody-induced arthritis (CAIA) were induced in SIGIRR-knockout mice. RESULTS: SIGIRR overexpression inhibited TLR-induced cytokine production in macrophages and DCs, while SIGIRR knockdown resulted in increased cytokine production following TLR stimulation. Moreover, SIGIRR overexpression inhibited the spontaneous release of cytokines by human RA synovial cells. The role of SIGIRR as an inhibitor of inflammation was confirmed in vivo, since SIGIRR(-/-) mice developed a more severe disease in both the ZIA and CAIA models. CONCLUSION: Our study is the first to show the expression pattern and function of SIGIRR in primary human cells. Furthermore, this investigation defines the role of SIGIRR in disease-relevant cell types and demonstrates that SIGIRR is a potential therapeutic target for RA.
20113367 Early activation of invariant natural killer T cells in a rheumatoid arthritis model and a 2010 Jun Invariant NKT (iNKT) cells are a distinctive subtype of CD1d-restricted T cells involved in regulating autoimmunity and capable of producing various T helper type 1 (Th1), Th2 and Th17 cytokines. Activation of iNKT cells by their exogenous ligand alpha-galactosylceramide (alpha-GalCer) exerts therapeutic effects in autoimmune diseases such as rheumatoid arthritis (RA). However, the pathophysiological role of iNKT cells in RA, in the absence of exogenous stimulation, is incompletely understood. We investigated the potential pathophysiological effects of iNKT cells in mice with collagen-induced arthritis (CIA), a model of RA. We found that iNKT cells underwent activation only in the early phases of the disease (6 days post-induction). In the liver, but not the spleen or lymph nodes, this early activation led to the release of interleukins -4, -17A and -10 and of interferon-gamma; and an increased CD69 expression. Importantly, clinical and histological signs of arthritis were improved by the functional blockade of iNKT cells by a monoclonal antibody to CD1d at the early phase of the disease. This improvement was associated on day 6 post-induction with decreased expression of co-stimulatory molecules (CD80, CD86, CD40) on splenic dendritic cells and macrophages, whereas regulatory T-cell suppressive effects and proportions were not modified. Taken in concert, these findings suggest that iNKT cells are activated early in the course of CIA and contribute to the pathogenesis of arthritis. Therefore, iNKT-cell activation may be a valid treatment target in RA.
19822067 A glimpse into the future: recombinant proteins and small molecules for targeted therapies 2009 Jul Whether the differences in the clinical picture and in the pathogenesis between rheumatoid arthritis (RA) and ankylosing spondylitis (AS) will lead to different therapeutic approaches is unclear at present. Since anti-TNF-alpha agents and other biologics are not efficacious in all patients new developments are clearly needed.
19404008 [Diagnostic utility of anti-cyclic citrullinated peptide antibody in early rheumatoid arth 2009 Apr Current therapeutic strategies against rheumatoid arthritis (RA) employ increasingly aggressive regimens from an early stage of the disease ; thus, serological markers more specific than IgM-rheumatoid factor (IgM-RF) are desirable. Anti-cyclic citrullinated peptide (anti-CCP) antibody has been reported as a useful and highly specificity marker for the diagnosis of RA. To clarify the diagnostic utility of anti-CCP antibody in early RA, we measured serum concentrations of anti-CCP antibody, IgM-RF, anti-agalactosyl IgG antibody and matrix metalloproteinase (MMP)-3 in 184 polyarthritis patients who showed onset symptoms within the previous 2 years. The diagnostic sensitivity of anti-CCP antibody in early RA was 60.0%, equivalent to IgM-RF (66.3%) and anti-agalactosyl IgG antibody (66.0%). Specificity, positive predictive values and diagnostic accuracy of anti-CCP antibody were the best among the four tested makers. In 38 patients who initially did not meet the ACR criteria for RA, but were diagnosed with RA during the course, the diagnostic sensitivity of anti-CCP antibody was 55.3%. On the other hand, the disease activity score (DAS) 28 of anti-CCP antibody positive and the negative patients was 5.16 and 5.34, respectively. Our data indicated that determination of anti-CCP antibody was useful for early diagnosis of RA.
19944432 Mortality after coronary artery revascularization of patients with rheumatoid arthritis. 2010 Jul OBJECTIVE: Patients with rheumatoid arthritis have an increased risk for accelerated atherosclerosis. It is not known, however, whether this disorder is associated with a higher risk of complications after coronary artery revascularization. METHODS: We conducted a cross-sectional study of patients in the 2003-2005 Nationwide Inpatient Sample. To determine whether patients with rheumatoid arthritis had higher in-hospital mortality after coronary artery revascularization, we used logistic regression to adjust for age, sex, race/ethnicity, income, rural-urban residency, diabetes, hypertension, hyperlipidemia, Charlson comorbidities (including myocardial infarction, congestive heart failure, and diabetes), elective admission, weekend admission, and primary payer. RESULTS: Among patients undergoing coronary artery revascularization, those with rheumatoid arthritis were 49% less likely to die while hospitalized compared with those without rheumatoid arthritis (odds ratio, 0.51; 95% confidence interval, 0.40-0.65) after adjusting for the above confounders. In subgroup analyses that adjusted for the same confounders, patients with rheumatoid arthritis also had a 61% improvement of in-patient mortality when they underwent percutaneous coronary interventions (odds ratio, 0.39; 95% confidence interval, 0.29-0.54) along with a median of 0.32 less days hospitalized (95% confidence interval, 0.28-0.34 days). Similarly, patients with rheumatoid arthritis undergoing coronary artery bypass grafting had a 31% improvement of in-patient mortality (odds ratio, 0.69; 95% confidence interval, 0.48-0.99), with a median of 1.36 less days hospitalized (95% confidence interval, 0.72-1.12 days). CONCLUSION: Among patients undergoing coronary artery revascularization, patients with rheumatoid arthritis have an in-hospital survival advantage along with reduced days of hospitalization compared with patients without rheumatoid arthritis.
21303477 The prevalence of rheumatoid factor isotypes and anti-cyclic citrullinated peptides in Mal 2011 Feb AIM: The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti-cyclic citrullinated peptides (anti-CCP) in Malaysian rheumatoid arthritis (RA) patients. METHODS: In this cross-sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme-linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second-generation anti-CCP were performed and the prevalence of each auto-antibody was compared in the three ethnic groups. RESULTS: The anti-CCP was the most prevalent auto-antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti-CCP-RF IgM combination provided the best test sensitivity. Seroprevalence of anti-CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti-CCP did not increase or decrease with advancing age, age at onset and disease duration. CONCLUSION: When used alone, anti-CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti-CCP assay, step-wise serum testing with IgM RF followed by anti-CCP may provide a more economically sensible option to optimize test sensitivity for RA.
20473500 HMG-CoA reductase inhibitor simvastatin suppresses Toll-like receptor 2 ligand-induced act 2011 Nov To investigate whether anti-inflammatory effects of HMG-CoA reductase inhibitor simvastatin (SMV) in rheumatoid arthritis (RA) is mediated by Toll-like receptor-2 (TLR-2) signal via inhibiting activation of RhoA, a small Rho GTPase that plays an important role in inflammatory responses. Peripheral blood monocytes from active RA patients were treated with Staphylococcus aureus peptidoglycan (PG), a ligand of TLR-2, in the presence or absence of SMV. RhoA activity was assessed by a pull-down assay. DNA-binding activity was measured by a sensitive multi-well colorimetric assay. Cytokine secretion was measured by ELISA. PG stimulation increased the level of active GTP-bound RhoA compared with unstimulated monocytes, and the effect of PG on RhoA activity was suppressed with anti-TLR-2 monoclonal antibody. RhoA inhibition either with a specific inhibitor or by siRNA transfection inhibited activation of NF-κB and secretion of TNFα and IL-1β in PG-induced RA monocytes. SMV mitigated PG-induced increase in RhoA activity and NF-κB activation as well as secretion of TNFα and IL-1β. The inhibitory effects of SMV were completely reversed by mevalonate and geranylgeranyl pyrophosphate. Our results indicate the modulation of RhoA on TLR-2-mediated inflammatory signaling in RA and provide a novel evidence for anti-inflammatory effects of statins through influencing TLR-2 signaling via RhoA in RA.
19022409 Serious infections during anti-TNFalpha treatment in rheumatoid arthritis patients. 2009 Jan The objective was to estimate the incidence of serious infections in the patients treated with anti-TNFalpha agents for rheumatoid arthritis (RA) recorded in the Lombardy Rheumatology Network (LORHEN) registry. The study inclusion criteria were met by 1064 of the 1114 patients with long-standing RA, 519 treated with infliximab, 303 with adalimumab, and 242 with etanercept; their mean age was 55.8 years and the mean duration of RA 9.4 years. Seventy-three patients (6.9%) experienced a total of 74 serious infections, an incidence rate for all treatment courses of 35.9 per 1000 patient-years (95% confidence interval [95% CI] 27.66-44.13). Most were lower respiratory tract (34.2%) or skin and soft tissue infections (20.5%). Of the 1064 patients, the 790 treated with anti-TNFalpha after March 2002 underwent screening tests for LTBI; five patients developed active tuberculosis. Three patients died of septic shock. The type of anti-TNFalpha agent did not seem to affect the incidence or site of the infections. Both univariate and multivariate analyses identified age at the start of anti-TNFalpha treatment (p=0.008), baseline erythrocyte sedimentation rate ([ESR] p=0.014), and the concomitant use of corticosteroids (p=0.029) as significant predictors of infections. There was no statistically significant difference in risk between the anti-TNFalpha agents.
19920093 Patient preferences in the choice of anti-TNF therapies in rheumatoid arthritis. Results f 2010 Feb OBJECTIVE: To identify the determinants of anti-TNF-naive patients' preferences for the route of administration of anti-TNF agents. METHODS: The study was carried out in 50 Italian rheumatology centres (802 patients). All patients completed a 31-item questionnaire addressing their perceptions of current treatment and the preferences for treatment with anti-TNF agents. Statistical methods included analysis of variance (ANOVA), t-test and chi-square test. RESULTS: The response rate to the questionnaire was 97.6%. At the time of the survey, 310 (39.9%) patients were dissatisfied with current treatments, owing to inefficacy, side effects and inconvenience of administration. The i.v. and s.c. routes of administration were preferred by 50.2 and 49.8%, respectively. No significant difference was found in patients by gender, age, RA duration or number of drugs used. Reasons for the choice of i.v. administration were the safety of treatment at the hospital and the reassuring effect of physician presence. The s.c. administration was chosen for the convenience of treatment and in particular for home treatment. Patients dissatisfied with current therapy due to side effects preferred s.c. administration (P = 0.029), whereas patients choosing the i.v. route had slightly higher scores on 'today pain' (P = 0.047) and 'articular pain' (P = 0.023) of the Rheumatoid Arthritis Disease Activity Index (RADAI). CONCLUSIONS: Both i.v. and s.c. treatments were well accepted by patients. However, treatment choice has to be discussed with patients, as individual preference seems to be determined by personal attitudes towards safety and convenience, by past experience and by the perception of current disease status.
20149313 Interleukin-6 gene -174 promoter polymorphism is associated with endothelial dysfunction b 2009 Nov OBJECTIVE: To determine whether the interleukin (IL)6 -174 gene polymorphism may influence the development of subclinical atherosclerosis manifested by the presence of endothelial dysfunction in RA patients. PATIENTS AND METHODS: 311 patients (228 [73.3%] women; 243 [78.1%] rheumatoid factor positive) who fulfilled the 1987 ACR classification criteria for RA seen at the Rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo between March 1996 and December 2006 and 226 matched controls were included in this study. Between March and December 2007, a subgroup of 98 patients randomly selected was assessed for the presence of endothelial dysfunction. Patients and controls were genotyped for a single biallelic (G/C) nucleotide polymorphism (rs1800795) in the promoter region at the position -174 of the IL6 gene using a TaqMan 5' allele discrimination assay. RESULTS: No significant differences in the IL6 -174 allele or genotype frequency between RA patients and controls were found. However, RA patients homozygous for the IL6 -174 GG genotype had more severe endothelial dysfunction (flow-mediated endothelium-dependent vasodilatation-FMD%: 4.2 + or - 6.6) than those carrying the IL6 -174 GC (FMD%: 6.3 + or - 8.1) or IL6 -174 CC (FMD%: 6.0 + or - 3.3) genotypes. In this regard, significant differences were observed when FMD% values in RA patients carrying the IL6 -174 GG genotype were compared with that observed in those carrying the IL6 -174 GC and the IL6 -174 CC genotypes (FMD%: 6.3 + or - 4.6) (p=0.02). CONCLUSIONS: Our results support a role of IL6 -174 gene polymorphism in the development of subclinical atherosclerosis in patients with RA.