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ID PMID Title PublicationDate abstract
21708910 Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheu 2011 Sep OBJECTIVE: To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients. METHODS: A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNFα inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifiable enrolment start date. RESULTS: 44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identified as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no significant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a significant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modified Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, significant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modified Sharp score. CONCLUSION: Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNFα inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials.
23194358 Conference scene: antigen-presenting cells: different approaches to immune induction and t 2012 Nov APCs are key players in the induction of T-cell responses. Accordingly, they have gained much attention as therapeutic targets for inflammatory diseases and cancer. Understanding their mode of action could serve in revealing novel approaches for the induction and blockade of T-cell immunity. This meeting has focused on recent advances in inducing the tolerogenic and immunostimulatory function of dendritic cells as well as current progress in the understanding of dendritic cell suppression through the CD4(+) Treg cell function.
20661741 Influence of Rituximab on markers of bone remodeling in patients with rheumatoid arthritis 2011 Feb Immune system and bone are interacting in a complex way. Rheumatoid arthritis is characterized not only by joint destruction, but also by development of systemic osteopenia and osteoporosis. The CD20-depleting antibody Rituximab (Rtx) is a novel therapeutic option able significantly to slow the destructive joint process of rheumatoid arthritis. However, there are little data whether Rtx influences systemic bone remodeling. In the present prospective study, we evaluated the influence of Rtx on markers of bone metabolism with a follow-up of 3-15 months after Rtx therapy (2 dose of each 1,000 mg) in 13 patients with rheumatoid arthritis. There was no significant change of the bone formation markers bone alkaline phosphatase and c-terminal propeptide of collagen I. However, a non-significant tendency of decrease of RANKL (with no chance of osteoprotegerin) and a significant decrease of the bone degradation marker desoxypyridinolin crosslinked collagen I was observed 15 months after Rtx application. These initial results provide no evidence of a negative systemic influence of Rtx on bone remodeling. In contrast, it appears that Rtx lowered osteoclast activity often found increased in active rheumatoid arthritis contributing to osteoporosis in this disease.
23079125 The CIMESTRA study: intra-articular glucocorticosteroids and synthetic DMARDs in a treat-t 2012 Jul OBJECTIVES: Treatment of early rheumatoid arthritis (RA) include aiming at disease control with early use of methotrexate (MTX) in monotherapy or in combination with glucocorticoids or other disease-modifying drugs (DMARDs). The CIMESTRA study applied an aggressive treatment with DMARD and intra-articular injections of glucocorticoids (i.a. GC) to control disease activity. This paper reviews the results of the five years' study. METHODS: 160 patients with early RA (<6 months duration) were randomized to receive MTX 7.5-20 mg/week+cyclosporine (CYA) 2.5-4 mg/kg (combination) or MTX+placebo-CYA (monotherapy). At each visit (week 0, 2, 4, 6, 8, thereafter monthly up to 24 months) patients had steroid injections in all swollen joints. During year 2, CYA/placebo was withdrawn, and hydroxychlorochine added. Clinical responses were assessed by ACR20, 50 and 70, ACR and DAS remission. Radiographic progression by x-rays of hands and feet. RESULTS: At year 1 (year 5) treatment responses in mono/combination groups were: ACR20: 68% (85%) / 85% (94%), ACR50: 53% (74%) / 68% (88%), ACR70: 44% (63%) / 59% (72%). After year 1, no significant differences between groups were found. Remission rates were: ACR-remission: 28% (52%) / 35% (60%), DAS28-remission: 34% (76%) / 43% (80%). Radiographic progression in both groups was <1TSS unit/year. After 1 and 2 years, 62% and 56% of the injected joints had not relapsed (both groups). Cumulated i.a.GC dose <1mg prednisolone/day. 19% received biologics by 5 years, 16% no treatment (sustained ACR-remission). Baseline magnetic resonance imaging (MRI) bone oedema best predicted radiographic progression after 2 years. Treatments were well tolerated. CONCLUSIONS: MTX and i.a.GC in a treat-to-target strategy over 5 years halted radiographic progression and induced remission in the majority of patients. I.a. GC had in long-lasting effect and cumulated dosages were low.
21805175 An association study of disease activity score components and patient satisfaction with ov 2012 Sep Patient overall satisfaction with health (PSH) was measured by a subset of questions from the Arthritis Impact Measurement Scales II. Based on longitudinal observations for 267 early rheumatoid arthritis (RA) patients of the United States Western Consortium (WC) cohort receiving first non-biologic DMARD treatment, we estimated the 1-year change in PSH (Δ PSH). Logistic regression analysis was used to estimate the association of improvement in Δ PSH with the core set of clinical and patient-reported components of disease activity scores (DAS). Most patients were more satisfied with health after 1 year of treatment (80%); few achieved DAS28-ESR minimal disease activity (27%) or remission (7%). Laboratory and joint count measures were not associated with improved 12-month PSH. Patients with greater HAQ-DI (P = 0.0473) and self-reported stiffness (P = 0.0669) were more likely to have a perceived overall health benefit from treatment. Regardless of objective disease status, patients are generally satisfied with first-line treatment, which could present a challenge to implementing DAS-guided treatment change. Patients with greater self-reported functional limitations might have lower expectations for treatment benefit and be less willing to modify their current therapy; subjective assessments of function and stiffness could be particularly useful in identifying these patients.
21742641 SIRT1 overexpression in the rheumatoid arthritis synovium contributes to proinflammatory c 2011 Oct OBJECTIVE: To analyse the expression of SIRT1 in synovial tissues and cells of patients with rheumatoid arthritis (RA) and to study the function of SIRT1 in inflammation and apoptosis in RA. METHODS: Levels of SIRT1 expression were analysed in synovial tissues and cells from patients with RA by real-time PCR and western blotting before and after stimulation with toll-like receptor ligands, tumour necrosis factor α (TNFα) and interleukin 1β (IL-1β). Immunohistochemistry was used to study the localisation of SIRT1. Fluorescence activated cell sorting analysis was performed to investigate the effect of SIRT1 on apoptosis. Peripheral blood monocytes and rheumatoid arthritis synovial fibroblasts (RASFs) were transfected with wild-type or enzymatically inactive SIRT1 expression vectors or with siRNA targeting SIRT1. Cytokine analysis of IL-6, IL-8 and TNFα were performed by ELISA to study the role of SIRT1 on proinflammatory mediators of RA. RESULTS: SIRT1 was found to be constitutively upregulated in synovial tissues and cells from patients with RA compared to osteoarthritis. TNFα stimulation of RASFs and monocytes resulted in further induced expression levels of SIRT1. Silencing of SIRT1 promoted apoptosis in RASFs, whereas SIRT1 overexpression protected cells from apoptosis. Inhibition of SIRT1 enzymatic activity by inhibitors, siRNA and overexpression of an enzymatically inactive form of SIRT1 reduced lipopolysaccharide-induced levels of TNFα in monocytes. Similarly, knockdown of SIRT1 resulted in a reduction of proinflammatory IL-6 and IL-8 in RASFs. CONCLUSION: The TNFα-induced overexpression of SIRT1 in RA synovial cells contributes to chronic inflammation by promoting proinflammatory cytokine production and inhibiting apoptosis.
22820623 Association of MIF-173G/C and MBL2 codon 54 gene polymorphisms with rheumatoid arthritis: 2012 Sep The aim of this study was to evaluate the association between macrophage migration inhibitory factor (MIF) -173G/C (rs755622), mannose-binding lectin (MBL2) exon 1 codon 54 (rs1800450) gene polymorphisms and rheumatoid arthritis (RA) susceptibility in ethnically different populations. A meta-analysis was conducted (allelic contrast, the additive model, the dominant model and the recessive model) on the MIF-173G/C polymorphism across five studies (four European and one Asian studies), and the MBL2 codon 54 polymorphism with five studies (four Asian and one European studies), respectively. Meta-analysis indicated an association between the MIF-173G/C in all study subjects in allelic contrast (OR=1.19, 95%CI: 1.05-1.35, P=0.001), the additive model (OR=1.68, 95CI: 1.13-2.49, P=0.001), the dominant model (OR=1.17, 95CI: 1.01-1.35, P=0.003), the recessive model (OR=1.63, 95CI: 1.10-2.42, P=0.001). While stratified by ethnicity with European populations, an association was found in allelic contrast (OR=1.20, 95CI: 1.04-1.38, P=0.002), the additive model (OR=1.85, 95CI: 1.19-2.88, P=0.001), the dominant model (OR=1.20, 95CI: 1.02-1.41, P=0.003). With respect to MBL2 codon 54 polymorphism and RA, no association was found in all study subjects in all comparisons, but there was an association while stratified by ethnicity with Asian populations in the dominant model (OR=1.50, 95CI: 1.01-2.23, P=0.007). In conclusion, the present study suggests that the MIF-173G/C polymorphism is associated with RA susceptibility, but the MBL2 codon 54 polymorphism is not associated with RA.
20740609 Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the W 2011 Feb OBJECTIVE: Farming and agricultural pesticide use has been associated with 2 autoimmune rheumatic diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, risk associated with other residential or work place insecticide use is unknown. METHODS: We analyzed data from the Women's Health Initiative Observational Study (n=76,861 postmenopausal women, ages 50-79 years). Incident cases (n=213: 178 for RA, 27 for SLE, and 8 for both) were identified based on self-report and use of disease-modifying antirheumatic drugs at year 3 of followup. We examined self-reported residential or work place insecticide use (personally mixing/applying by self and application by others) in relation to RA/SLE risk, overall and in relation to farm history. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were adjusted for age, race, region, education, occupation, smoking, reproductive factors, asthma, other autoimmune diseases, and comorbidities. RESULTS: Compared with never used, personal use of insecticides was associated with increased RA/SLE risk, with significant trends for greater frequency (HR 2.04, 95% CI 1.17-3.56 for ≥6 times/year) and duration (HR 1.97, 95% CI 1.20-3.23 for ≥20 years). Risk was also associated with long-term insecticide application by others (HR 1.85, 95% CI 1.07-3.20 for ≥20 years) and frequent application by others among women with a farm history (HR 2.73, 95% CI 1.10-6.78 for ≥6 times/year). CONCLUSION: These results suggest residential and work place insecticide exposure is associated with the risk of autoimmune rheumatic diseases in postmenopausal women. Although these findings require replication in other populations, they support a role for environmental pesticide exposure in the development of autoimmune rheumatic diseases.
22402800 Associations between TNFAIP3 gene polymorphisms and rheumatoid arthritis: a meta-analysis. 2012 Jun OBJECTIVE: The aim of this study was to determine whether tumor necrosis factor alpha inducible protein 3 (TNFAIP3) polymorphisms confer susceptibility to rheumatoid arthritis (RA) in ethnically different populations. METHODS: The authors conducted meta-analyses on associations between the TNFAIP3 polymorphisms and RA susceptibility. RESULT: A total of ten comparative studies were included in this meta-analysis, which showed an association between the two allele of rs6920220 and RA in all study subjects [odds ratio (OR) 1.216, 95% confidence interval (CI) 1.166-1.269, p < 1.0 × 10(-9)]. The two allele of rs6920220 was also significantly associated with RA in Europeans only (OR 1.227, 95% CI 1.175-1.282, p < 1.0 × 10(-9)). Meta-analysis revealed no association between the two allele of the rs10499194 polymorphism and RA in Europeans, but a significant association was found in Asians (OR 1.254, 95% CI 1.101-1.429, p=6.7 × 10(-4)). Furthermore, an association was found between the two allele of rs2230926 and RA in all study subjects (OR 1.390, 95% CI 1.214-2.331, p=1.9 × 10(-6)). CONCLUSIONS: This meta-analysis confirms that the TNFAIP3 polymorphisms are associated with RA susceptibility in different ethnic groups, namely, in Europeans for rs6920220 and in Asians for rs10499194.
22287501 Evaluation of finger joint synovial vascularity in patients with rheumatoid arthritis usin 2012 Mar PURPOSE.: To assess synovial microvascularity in finger joints with rheumatoid arthritis (RA) by contrast-enhanced ultrasound (CEUS), distinguishing between cases of active disease and those in remission; to standardize the technique for software analysis. METHODS.: Fifty-two finger joints of RA patients (26 with active disease and 26 in remission) were immersed in water and examined by CEUS using a fixed probe. Signal intensity curves were calculated with the software. RESULTS.: Contrast enhancement was detectable in all 26 patients with active RA (100%), but not in 25 of 26 patients in remission (96%); one of the latter patients (4%) showed minimal enhancement. The method's sensitivity and specificity in distinguishing active disease from remission were 100% and 96%. The grades of synovial enhancement correlated with clinical disease activity and software flow parameters. The peak contrast levels correlated with clinical activity, a peak of 9% representing the cutoff between remission and active disease. CONCLUSIONS.: CEUS with a fixed probe on finger joints immersed in water detected synovial vascularization in RA, producing results suitable for standardized software analysis and avoiding artifacts.
22886712 Treatment patterns in the first year after initiating tumor necrosis factor blockers in re 2012 Aug BACKGROUND: Tumor necrosis factor (TNF)-blockers are approved for use in several immune-related conditions, but treatment patterns, such as switching between TNF blockers or restarting treatment after a gap in therapy, are not clearly established. This analysis examined TNF blocker treatment patterns within the first year after initiating treatment with etanercept, adalimumab, or infliximab in patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. METHODS: Administrative claims data from the MarketScan® Commercial Claims and Encounters Database (Thomson Reuters, Ann Arbor, MI, USA) were analyzed for patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis who were continuously enrolled and newly initiated etanercept, adalimumab, or infliximab treatment between January 1, 2005 and July 1, 2009. Persistence (no treatment gap ≥45 days), restarting index therapy (after a ≥45-day treatment gap), switching to a different biologic of interest (certolizumab, golimumab, ustekinumab, alefacept, abatacept, rituximab, or tocilizumab), and stopping (≥45-day treatment gap with no restart or switch) were analyzed for the first year after the index date. RESULTS: A total of 8,454 patients had an index claim for etanercept (n = 4,224), adalimumab (n = 2,941), or infliximab (n = 1,289). Treatment patterns in the first year across all four conditions combined for etanercept, adalimumab, or infliximab, respectively, were: persistence, 42%, 47%, and 56%; restarting, 25%, 19%, and 12%; switching, 13%, 12%, and 13%; and stopping, 20%, 22%, and 19%. The combined rates of either persistence or restarting initial therapy after a treatment gap were 67%, 66%, and 68%, for etanercept, adalimumab, and infliximab, respectively. Most switches (66-92%) were between the three TNF blockers. CONCLUSION: In the first year after initiating TNF blocker therapy, patients often have a ≥45-day treatment gap; however, approximately two-thirds of patients are either persistent with or restart their index therapy in the year following TNF blocker initiation.
22233170 A selective and potent CXCR3 antagonist SCH 546738 attenuates the development of autoimmun 2012 Jan 10 BACKGROUND: The CXCR3 receptor and its three interferon-inducible ligands (CXCL9, CXCL10 and CXCL11) have been implicated as playing a central role in directing a Th1 inflammatory response. Recent studies strongly support that the CXCR3 receptor is a very attractive therapeutic target for treating autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and psoriasis, and to prevent transplant rejection. We describe here the in vitro and in vivo pharmacological characterizations of a novel and potent small molecule CXCR3 antagonist, SCH 546738. RESULTS: In this study, we evaluated in vitro pharmacological properties of SCH 546738 by radioligand receptor binding and human activated T cell chemotaxis assays. In vivo efficacy of SCH 546738 was determined by mouse collagen-induced arthritis, rat and mouse experimental autoimmune encephalomyelitis, and rat cardiac transplantation models. We show that SCH 546738 binds to human CXCR3 with a high affinity of 0.4 nM. In addition, SCH 546738 displaces radiolabeled CXCL10 and CXCL11 from human CXCR3 with IC50 ranging from 0.8 to 2.2 nM in a non-competitive manner. SCH 546738 potently and specifically inhibits CXCR3-mediated chemotaxis in human activated T cells with IC90 about 10 nM. SCH 546738 attenuates the disease development in mouse collagen-induced arthritis model. SCH 546738 also significantly reduces disease severity in rat and mouse experimental autoimmune encephalomyelitis models. Furthermore, SCH 546738 alone achieves dose-dependent prolongation of rat cardiac allograft survival. Most significantly, SCH 546738 in combination with CsA supports permanent engraftment. CONCLUSIONS: SCH 546738 is a novel, potent and non-competitive small molecule CXCR3 antagonist. It is efficacious in multiple preclinical disease models. These results demonstrate that therapy with CXCR3 antagonists may serve as a new strategy for treatment of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, and to prevent transplant rejection.
21358058 [Encounter of cancer cells with bone. In vivo imaging of osteoclasts and their precursors 2011 Mar Osteoclasts play critical roles not only in normal bone homeostasis ('remodeling') , but also in the pathogenesis of bone destructive disorders such as osteoporosis, rheumatoid arthritis, and bone metastasis. However, it has not been known how osteoclast precursor monocytes migrate into the bone surface and what controls their migratory behaviors. To reveal these systems, we have recently established a new system for visualizing intact bone tissues and bone marrow cavities in live animals by using an advanced imaging technique with intravital two-photon microscopy. By means of the system we have revealed that sphingosine-1-phosphate (S1P) , a lipid mediator, dynamically regulates migration and localization of osteoclasts and their precursors in vivo . Here we show the latest data and the detailed methodology of intravital imaging of bone tissues, and also discuss its further application.
22923178 A safety analysis of oral prednisone as a pretreatment for rituximab in rheumatoid arthrit 2012 Nov The administration of 100 mg of methylprednisolone intravenously (IV) 1/2 h prior to rituximab decreases the incidence of acute infusion reactions (AIRs). However, this pretreatment adds considerable time and conveys potential risk. We performed an open-label prospective assessment of oral prednisone as a pretreatment to rituximab. This was a 26-week open-label trial of 40 mg of oral prednisone given 1/2 h prior to rituximab as a prophylaxis against AIRs in patients with rheumatoid arthritis (RA). The primary endpoint was AIRs in the first 24 h after their initial infusion. Secondary endpoints include AIRs during the 24 h following their second infusion and any adverse events experienced during the 26-week study; efficacy measures were also followed as secondary endpoints. Sixty-four subjects were screened, and 50 subjects qualified. Fourteen out of the 50 (28 %) subjects had AIRs within 24 h of their first infusion. There were four AIRs (8.3 %) within 24 h of their second infusion. One of day 0 AIRs required drug discontinuation (wheezing/bronchospasm). Forty out of 50 (80 %) subjects experienced an adverse event during the 26 weeks. There were three SAEs deemed not to be study-drug related. The DAS28 and HAQ-DI all improved significantly at weeks 8, 16, and 26 compared to baseline. Historical controls demonstrate that 27 % of RA subjects experience AIRs with their first rituximab infusion. Our data suggest a smaller dose of oral prednisone is an effective alternative to IV methylprednisolone as a pretreatment for rituximab in patients with RA.
21778909 Rheumatoid arthritis decision making: many information sources but not all rated as useful 2011 Aug BACKGROUND: Patients who make high-quality medical decisions are more likely to have better health outcomes. One of the central components to a high-quality decision is the well-informed manner in which it is made. However, there has been little research studying patient behaviors regarding how they seek information about treatments for rheumatoid arthritis (RA). METHODS: We conducted a pilot study surveying beneficiaries of a health plan who had 2 or more visits coded for RA. Of 799 invited subjects, 101 (13%) completed interviews. Participants answered a questionnaire regarding sources of RA treatment information and their usefulness, sociodemographic items, and scales regarding their attitudes toward providers and medicines. Outcomes of interest included the average number of sources described (range, 0-10) and the usefulness for each source (1 "not useful" and 4 "extremely useful"). RESULTS: Methotrexate was the most widely used medication reported. The mean (SD) number of information sources used was 5.0 (2.1). Participants rated the information they used with a mean (SD) score of 2.8 (0.7). We found no strong patient correlates of these outcomes when compared with the aforementioned domains. Of the 98% of the total sample who referred to a rheumatologist for information, 87% rated the source as extremely useful. The Internet was the most frequently used nonprovider source, with 63% of subjects reporting use, and a mean (SD) usefulness rating of 3.0 (1.03). CONCLUSIONS: In this pilot study, participants used many sources of information regarding treatment decisions for RA. Ninety-eight percent of the participants used rheumatologists as a source and found them extremely useful. Of the nonprovider sources, the Internet was most common, and 40% found it very useful.
21764200 Temporomandibular joint problems and periodontal condition in rheumatoid arthritis patient 2011 Dec PURPOSE: There are conflicting reports as to whether patients with rheumatoid arthritis (RA) are at high risk for periodontal disease (PD). However, analogous mechanisms of tissue destruction have been reported for the 2 conditions. The present study was undertaken to determine temporomandibular joint (TMJ) problems and periodontal conditions in patients with RA in relation to their rheumatologic status and identify their periodontal needs. MATERIALS AND METHODS: One hundred patients with PD, 50 with RA and 50 without RA, were assigned to 1 of 2 age groups (30 to 39 or 40 to 50 years). The plaque index, bleeding index, clinical attachment loss, radiographic bone loss, tooth loss, and TMJ problems were assessed in the 2 groups. Disease duration, level of erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire, and Verbal Descriptor Pain Scale score were assessed in the RA group. RESULTS: Patients with RA were predominantly women, with longer illness duration (11.84 years), higher ESR (32.08 mm/hour), and higher scores on the Health Assessment Questionnaire (0.82). Patients with RA were characterized by significant increases in clinical attachment loss (3.24 mm), bone loss (1.79 mm), missing teeth (6.22), and TMJ problems (54%) than controls. Their periodontal status significantly correlated with illness duration, Health Assessment Questionnaire score, and Verbal Descriptor Pain Scale score. However, no difference in plaque index and bleeding index were observed between the RA and control groups. Unexpectedly, 30- to 40-year-old patients with RA had a significantly higher plaque index (1.54) and greater TMJ deviation (15%) than the older subjects. CONCLUSION: Patients with advanced RA are more likely to develop more significant periodontal and TMJ problems compared with patients with PD and without RA. There is a great need to instruct patients with RA to consult a dentist to at least decrease PD severity.
21169855 Disease-modifying antirheumatic drugs increase serum adiponectin levels in patients with r 2011 Jan BACKGROUND: Adiponectin is an adipocyte-derived adipokine with immunosuppressive and anti-inflammatory properties. It also decreases expression of adhesion molecules. In terms of its relationship with acute-phase reactants, there are conflicting results in patients with rheumatoid arthritis (RA). OBJECTIVES: The objectives of this study were to evaluate the levels of adiponectin in RA patients before and after the treatment with disease-modifying antirheumatic drugs (DMARDs) and to evaluate whether there is a correlation between adiponectin levels and disease activity and acute-phase-response reactants (APRRs). METHODS: Serum adiponectin levels, APRRs, total and high-density lipoprotein cholesterol (HDL-C), body mass index, and body fat mass were measured in 27 patients with RA before and after the treatment with DMARDs plus prednisolone. An inclusion criterion for RA patients was to be DMARD naive for at least 6 months or to have been newly diagnosed with RA. Twenty patients with osteoarthritis were included in this study as a disease control. RESULTS: No significant difference was found between RA and osteoarthritis group in terms of baseline adiponectin level. Mean adiponectin level and mean HDL-C level increased significantly compared with mean baseline level after the treatment with DMARDs plus prednisolone (10 [SD, 4.9] vs. 13.9 [SD, 8.7] μg/mL; P < 0.001; 56.8 [SD, 19] vs. 65 [SD, 18] mg/dL, P < 0.004, respectively). APRRs and the 28-joint-count disease activity score decreased significantly at the end of the 3 months of therapy. The adiponectin levels tended to be negatively correlated with acute-phase reactants and disease activity, although no changes were significant. There was a positive correlation between HDL-C and adiponectin levels at 3 month (r = 0.53, P < 0.001). No correlation was found between erythrocyte sedimentation rate and adiponectin levels both at baseline and at 3 months. CONCLUSION: Adiponectin levels can be modified by effective treatment of rheumatoid arthritis. This suggests that active inflammation may decrease serum adiponectin levels. In consideration of the antiatherogenic and anti-inflammatory features of adiponectin, increased adiponectin levels in patients with RA may result in a more favorable cardiovascular profile.
22034041 rAAV human trial experience. 2011 Recombinant AAV vectors have been used in clinical trials since the mid-1990s, with over 300 subjects enrolled in studies. Although there are not yet licensed AAV products, there are several clear examples of clinical efficacy, and recombinant AAV vectors have a strong safety record after administration both locally and systemically. This chapter provides a review of two types of studies that have shown efficacy, including studies for Leber's congenital amaurosis, a hereditary retinal degenerative disorder in which subretinal administration of AAV has shown efficacy in terms of improvement in multiple measures of visual/retinal function; and of Parkinson's disease which has also shown improvement in clinical and imaging studies after gene transfer to the CNS. The chapter also provides a detailed review of the results of studies of gene therapy for hemophilia, in which short-term efficacy was achieved, but expression of the donated gene failed to persist, likely due to an immune response to the vector. Safety issues relating to AAV-mediated gene transfer are discussed, including a detailed review of the single death to have occurred in an AAV gene therapy trial (likely unrelated to the AAV vector), and of issues related to integration and insertional mutagenesis, risk of germline transmission, and risks related to immune responses to either vector or transgene product. Finally, protocols for determining the presence of vector DNA in body fluids using real-time quantitative PCR, and for isolating, cryopreserving, and testing peripheral blood mononuclear cells for interferon-γ (IFN-γ) responses to capsid are described in detail.
21672203 Baseline characteristics and patient reported outcome data of patients prescribed etanerce 2011 Jun 14 BACKGROUND: The anti-TNF inhibitor, etanercept is administered as a once or twice weekly subcutaneous injection for the treatment of rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis (JIA). Limited data from the patients' perspective are available on the use of biologics in the treatment of these chronic conditions and this evaluation was designed to collect data from patients who had been prescribed etanercept for the first time. This manuscript describes the self-reported baseline characteristics and health-related quality of life of patients prior to treatment. Follow-up data will be reported separately. METHODS: Patients throughout the United Kingdom prescribed etanercept were invited to participate in an evaluation of their condition and treatment using a data collection tool consisting of a web-based system supplemented by telephone reporting (PROBE). Outcome measures reported at baseline included demographic data, the condition being treated, previous treatment with biologic agents and current and previous medications. Questions modified from standard, validated quality of life questionnaires such as EQ-5D were incorporated and patients made a global assessment of the severity of their own illness using the CGI-S scale. RESULTS: A total of 344 patients/carers/parents participated in the evaluation at baseline, 290 (84%) by online questionnaire and 54 (16%) by telephone. Overall, the study population had a mean age of 53 years, was predominantly female (62%) and 20% had been previously treated with a biologic agent. A total of 191 (56%) patients were receiving treatment with etanercept for rheumatoid arthritis, 44 (13%) for psoriatic arthritis, 43 (13%) for ankylosing spondylitis, 35 (10%) for psoriasis, 9 (3%) for known juvenile idiopathic arthritis (JIA) and 22 (6%) for another condition/patient unsure/missing response. All patients were prescribed the 50 mg weekly dose of etanercept except for 1 patient with JIA (40 mg) dose and 2 patients with psoriasis (100 mg). Thirty-eight percent of patients with rheumatoid arthritis were not receiving treatment with methotrexate. CONCLUSIONS: The baseline characteristics and health-related quality of life of first time users of etanercept can be adequately described using self-reported patient data collected using an online questionnaire with a telephone option (PROBE).
22309893 Low copy number of the FCGR3B gene and rheumatoid arthritis: a case-control study and meta 2012 Feb 7 INTRODUCTION: Low copy number (CN) of the Fc gamma receptor 3B (FCGR3B) gene has been associated with systemic autoimmune disease. This receptor for IgG is present almost exclusively on neutrophils and plays a role in their interaction with immune complexes. At present the relationship between FCGR3B and rheumatoid arthritis (RA) is unclear. The aim of the present study was to investigate whether low CN of the FCGR3B gene is associated with susceptibility to RA. METHOD: The FCGR3B CN was determined using a custom Taqman® CN assay (Hs04211858; Applied Biosystems, Foster City, CA, USA) in 197 RA patients, recruited from a tertiary setting, and in 162 population matched controls. Odds ratios for low CN (< 2) and high CN (> 2), both relative to the normal diploid 2CN, were estimated by logistic regression. RESULTS: A significant association between RA and low FCGR3B CN was observed, with frequencies of 13.7% in RA patients compared with 6.2% in controls (odds ratio 2.5, 95% confidence interval 1.2 to 5.4, P = 0.017). No association was observed between low CN and the presence of rheumatoid factor, anti-cyclic citrullinated peptide antibodies or radiographic erosions in RA patients. A meta-analysis including six previous studies confirmed an association between RA and low FCGR3B CN (odds ratio 1.47, 95% confidence interval 1.13 to 1.92, P = 0.004). CONCLUSIONS: The present study confirms that a low CN of the FCGR3B gene is associated with susceptibility to RA. The association may be stronger in patients recruited from a tertiary setting, which may relate to disease severity and/or complications. The mechanism of susceptibility remains unclear and further study is required.