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ID PMID Title PublicationDate abstract
23221145 Influenza vaccination in autoimmune rheumatic disease patients. 2013 Jan Patients suffering from autoimmune rheumatic diseases have significantly higher risk of developing various infections compared to the healthy population. Our study included patients suffering from systemic lupus erythematosus (n = 30), rheumatoid arthritis (n = 37) or Sjögren's syndrome (n = 32), with stable underlying diseases status. In November 2010, 47 patients, including 35 subjects vaccinated annually during 2006-2010, received immunization against influenza with trivalent inactivated split vaccine, whereas 52 patients did not accept proposed vaccination in that period. The presence of viral (primarily influenza) and bacterial infections, parameters of disease activity (from the date of vaccination until April 2011), and titers of antibodies against A H1N1 were then monitored in vaccinated and unvaccinated patients. We have identified the importance of predisposing factors for influenza occurrence (i.e. previous respiratory infections and vaccinations in last five years, age, sex, type of disease and duration, medications, smoking) in those groups of patients. The incidence of influenza or bacterial complications (bronchitis) among vaccinated patients was significantly lower, compared to the non-vaccinated group. Importantly, there was no case of exacerbation of the underlying disease. The last vaccination in 2010 reduced the risk of influenza by 87%, but previous bacterial infections (bronchitis and pneumonia) increased influenza risk significantly. In the present study, we have shown the efficiency, sufficient immunogenicity and safety of modern influenza vaccine application in patients suffering from systemic lupus erythematosus, rheumatoid arthritis or Sjögren's syndrome.
23434570 Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triam 2014 Apr OBJECTIVES: An investigator-initiated, double-blinded, placebo-controlled, treat-to-target protocol (Clinical Trials:NCT00660647) studied whether adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment in early rheumatoid arthritis (ERA) increased the frequency of low disease activity (DAS28CRP<3.2) at 12 months. METHODS: In 14 Danish hospital-based clinics, 180 disease-modifying anti-rheumatic drugs (DMARD)-naïve ERA patients (<6 months duration) received methotrexate 7.5 mg/week (increased to 20 mg/week within 2 months) plus adalimumab 40 mg every other week (adalimumab-group, n=89) or methotrexate+placebo-adalimumab (placebo-group, n=91). At all visits, triamcinolone was injected into swollen joints (max. four joints/visit). If low disease activity was not achieved, sulfasalazine 2 g/day and hydroxychloroquine 200 mg/day were added after 3 months, and open-label biologics after 6-9 months. Efficacy was assessed primarily on the proportion of patients who reached treatment target (DAS28CRP<3.2). Secondary endpoints included DAS28CRP, remission, Health Assessment Questionnaire (HAQ), EQ-5D and SF-12. Analysis was by intention-to-treat with last observation carried forward. RESULTS: Baseline characteristics were similar between groups. In the adalimumab group/placebo group the 12-month cumulative triamcinolone doses were 5.4/7.0 ml (p=0.08). Triple therapy was applied in 18/27 patients (p=0.17). At 12 months, DAS28CRP<3.2 was reached in 80%/76% (p=0.65) and DAS28CRP was 2.0 (1.7-5.2) (medians (5th/95th percentile ranges)), versus 2.6 (1.7-4.7) (p=0.009). Remission rates were: DAS28CRP<2.6: 74%/49%, Clinical Disease Activity Index≤2.8: 61%/41%, Simplified Disease Activity Index<3.3: 57%/37%, European League Against Rheumatism/American College of Rheumatology Boolean: 48%/30% (0.0008
25472447 A new family of choline kinase inhibitors with antiproliferative and antitumor activity de 2015 Jan BACKGROUND: Choline kinase alpha (ChoKα) is a critical enzyme in the synthesis of phosphatidylcholine, a major structural component of eukaryotic cell membranes. ChoKα is overexpressed in a large variety of tumor cells and has been proposed as a target for personalized medicine, both in cancer therapy and rheumatoid arthritis. MATERIALS AND METHODS: Triterpene quinone methides (TPQ) bioactive compounds isolated from plants of the Celastraceae family and a set of their semisynthetic derivatives were tested against the recombinant human ChoKα. Those found active as potent enzymatic inhibitors were tested in vitro for antiproliferative activity against HT29 colorectal adenocarcinoma cells, and one of the active compounds was tested for in vivo antitumoral activity in mice xenographs of HT29 cells. RESULTS: Among 59 natural and semisynthetic TPQs tested in an ex vivo system, 14 were highly active as inhibitors of the enzyme ChoKα with IC50 <10 μM. Nine of these were potent antiproliferative agents (IC50 <10 μM) against tumor cells. At least one compound was identified as a new antitumoral drug based on its in vivo activity against xenographs of human HT-29 colon adenocarcinoma cells. CONCLUSIONS: The identification of a new family of natural and semisynthetic compounds with potent inhibitory activity against ChoKα and both in vitro antiproliferative and in vivo antitumoral activity supports further research on these inhibitors as potential anticancer agents. Their likely role as antiproliferative drugs deserves further studies in models of rheumatoid arthritis.
22526833 A review of tocilizumab treatment in 122 rheumatoid arthritis patients included in the Tsu 2013 Mar OBJECTIVES: Biologics have transformed the treatment of rheumatoid arthritis. Clinical remission is now the goal. We sought to verify whether the administration of tocilizumab-a biologic-can help to achieve current treatment goals. METHODS: Using data from the Tsurumai Biologics Communication Registry for 122 patients treated with tocilizumab, we evaluated changes in DAS28-ESR at 12 months after initiation, and also evaluated remission rates defined using conventional and new Boolean-based remission criteria. We divided 50 patients who had received tocilizumab as a first-line treatment into two groups [disease duration at baseline of 12 months or less (≤12 M) and more than 12 months (>12 M)]. RESULTS: At 12 months after initiation, there was no difference in DAS28-ESR, and remission rates based on the conventional criterion were also comparable (50 % in both groups). However, under the new criterion, remission was 50.0 % in the ≤12 M group against 12.5 % in the >12 M group (p = 0.0181). Among the individual components of the new remission criterion, the small proportion of patients in the >12 M group with a patient global assessment (PtGA) of ≤1 had a particularly strong influence on the remission rate for that group, but this component was not as important for the ≤12 M group. CONCLUSIONS: When used as a first-line biological drug for patients with early-stage RA (≤12 M), tocilizumab appears to provide high rates of remission under the Boolean-based remission criterion, which were strongly affected by the PtGA.
23750475 Characterization of monoclonal antibodies against a human chondrocyte surface antigen. 2013 Jun Chondrocytes express a number of cell-surface molecules that mediate cell-cell or cell-matrix interactions. Identification and full characterization of new chondrocyte surface molecules will lead to a better understanding of the function of the chondrocyte. Researchers used primary human chondrocytes as an immunogen, and various monoclonal antibodies (MAbs) were generated using standard hybridoma technology. A monoclonal antibody named 5D2 was selected for further characterization. The antigen recognized by 5D2 MAb is expressed by primary human chondrocytes, primary synovial fibroblasts, synovial fibroblast cell lines (SW982), primary skin fibroblasts, and osteoblasts, but not expressed in blood cells. Biochemical analysis revealed that the 5D2 antigen is a protein with a molecular weight of approximately 25-35 kDa. Protein identification by mass spectrometry and molecular cloning revealed that 5D2 antigen is identical to the Thy-1 molecule. Furthermore we confirmed this specificity of the antibody by the isolated and cloned Thy-1 gene to the COS-7 and probed it with the 5D2 antibody using Western blot analysis. We examined the role of the Thy-1 molecule in arthritis models and tissue; one was papain-induced rat arthritis, the other was immunohistological staining of osteoarthritic (OA) human articular cartilage. OA cartilage showed a higher expression of Thy-1 as compared with normal tissue in all experimental approaches. The in vitro studies showed that the inflammatory cytokine interleukin-1β up-regulated Thy-1 molecule expression in the cartilage tissue. It can be concluded that the Thy-1 might be a potential biomarker for cartilage pathogenesis, degradation, and metabolic turnover.
24886568 Sick leave patterns in common musculoskeletal disorders--a study of doctor prescribed sick 2014 May 24 BACKGROUND: Comparative data on sick leave within musculoskeletal disorders (MSDs) is limited. Our objective was to give a descriptive overview of sick leave patterns in different MSDs. METHODS: Using electronic medical records, we collected information on dates and diagnostic codes for all available sick leave certificates, during 2 years (2009-2010), in the North Western part of the Skåne region in Sweden (22 public primary health care centres and two general hospitals). Using the International Classification of Diseases (ICD) 10 codes on the certificates we studied duration, age and sex distribution and recurrent periods of sick leave for six strategically chosen MSDs; low back pain (M54) disc disorders (M51), knee osteoarthritis (M17) hip osteoarthritis (M16) rheumatoid arthritis (M05-M06) and myalgia (M79). RESULTS: All together 20 251 sick leave periods were issued for 16 673 individuals 16-64 years of age (53% women). Out of the selected disorders, low back pain and myalgia had the shortest sick leave periods, with a mean of 26 and 27 days, respectively, while disc disorders and rheumatoid arthritis had the longest periods with a mean of 150 and 147 days. For low back pain and myalgia 27% and 26% of all sick leave was short (8-14 days) and only 11% and 13%, were long (≥90 days). For the other selected MSDs, less than 5% of the periods were short. For disc disorders, hip osteoarthritis and rheumatoid arthritis, more than 60% of the periods were long (p > 0.001). For back disorders and myalgia most periods were issued in the age groups between 40-49, with similar patterns for women and men. Osteoarthritis and rheumatoid arthritis had most periods in the age groups of 50-64, and patterns for women and men differed. Low back pain, rheumatoid arthritis and myalgia had the greatest share of recurrent sick leave (31%, 34% and 32% respectively). CONCLUSION: Duration, age and sex distribution and numbers of recurrent sick leave varies considerably between different MSDs. This underscores the importance of using specified diagnosis, in sick leave research as well as in planning of treatment and rehabilitation and evaluation of prognosis.
24269925 Roles of the protein tyrosine phosphatase PTPN22 in immunity and autoimmunity. 2013 Dec PTPN22 is a protein tyrosine phosphatase expressed by the majority of cells belonging to the innate and adaptive immune systems. Polymorphisms in PTPN22 are associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and type 1 diabetes. This review discusses the role of PTPN22 in T and B cells, and its function in innate immune cells, such as monocytes, dendritic cells and NK cells. We focus particularly on the complexity that underlies the function of PTPN22 in the biological processes of the immune system; such complexity has led various research groups to produce rather conflicting data.
25062652 Cost of biologics per treated patient across immune-mediated inflammatory disease indicati 2014 Aug 1 PURPOSE: Pharmacy benefits management companies have emerged as the national standard for the management of prescription drugs in the United States. The objective of this study was to estimate the annual costs per treated patient of 8 biologics indicated for select immune-mediated inflammatory diseases: moderate to severe rheumatoid arthritis, moderate to severe plaque psoriasis, active psoriatic arthritis, and/or active ankylosing spondylitis. METHODS: Using the Medco pharmacy benefits-management database, data from patients aged 18 to 63 years with ≥1 claim for abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, or ustekinumab, dated between January 1, 2008 and August 31, 2011, were collected. Eligible patients were continuously enrolled for ≥180 days before and 360 days after the date of the first biologic claim (index date), and had ≥1 claim associated with a diagnosis of rheumatoid arthritis, moderate to severe plaque psoriasis, active psoriatic arthritis, and/or active ankylosing spondylitis in the 180 days before or 30 days after the index date. The annual total costs per treated patient were calculated as the total dose of the index biologic and all other biologics for which there was a claim in the postindex period, multiplied by the wholesale acquisition cost as of October 1, 2013, plus the costs associated with administrations (calculated as number of infusions multiplied by the 2013 Medicare Physician Fee Schedule costs). FINDINGS: Within the study population (N = 8306; 5356 (64.5%) women, 2950 men (35.5%), average age: 42.3 years (SD: 10.0)), the most commonly used biologics were etanercept (43.1%), adalimumab (31.0%), and infliximab (17.0%), which accounted for 91.1% of all biologic prescriptions. Total costs per treated patient across indications were as follows: adalimumab, $23,427 to $26,304; infliximab, $22,824 to $28,907; and etanercept, $21,468 to $27,748, whereas abatacept, certolizumab, golimumab, rituximab, and ustekinumab were associated with a larger range: $17,017 to $41,888. IMPLICATIONS: The present study provides insight into the prescribing patterns and cost differences among 8 biologic agents used for the treatment of immune-mediated inflammatory diseases. This information may prove useful when designing a pharmacy benefits-management formulary.
24038595 Identifying newly approved medications in Medicare claims data: a case study using tociliz 2013 Nov BACKGROUND: After U.S. licensure, parenterally administered medications are identified using non-specific drug codes. Accurately identifying these medications is critical to safety and effectiveness research. Methods to identify medications prior to assignment of specific drug codes have not been well described. OBJECTIVES: To describe a generalized approach using non-specific drug codes to identify parenteral therapies in Medicare claims and to assess the ability of that approach to identify tocilizumab (TCZ), a new biologic agent approved in 2010. METHODS: We used 2008-2010 Medicare data for a cohort of rheumatoid arthritis patients for algorithm development. Our algorithm classified non-specific drug codes based upon: 1) ICD9 codes; 2) unit values (i.e. dose); 3) codes for infusion/injection procedures; 4) expected versus observed total reimbursement amount and reimbursement per unit. We assessed algorithm performance by linking to an arthritis registry to examine external validity. RESULTS: Of 472 803 claims with non-specific drug codes, 9762 claims satisfied the TCZ algorithm. 74.3% of 9762 claims were classified as TCZ by exact unit price or allowed amount, 4.4% by unique doses, 21.3% by diagnosis code and small deviation from unit price or allowed amount. The algorithm demonstrated good performance characteristics: sensitivity 94% (95% CI 80-99), specificity 100% (99-100) and PPV 97% (84-100). CONCLUSION: Claims-based algorithms in Medicare or similar data systems can accurately identify newly approved biologics administered parenterally prior to the assignment of specific drug codes.
24733191 Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active r 2015 Jun OBJECTIVES: To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA). METHODS: Design: a multicentre, open-label, randomised controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen. INTERVENTION: 207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5 mg once a week, or TwHF 20 mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24. RESULTS: 174/207 (84.1%) patients completed 24 weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216). CONCLUSIONS: TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA. TRIAL REGISTRATION NUMBER: NCT01613079.
23662580 [Influence of antibodies to DNA on MDCK cells and their intracellular localization]. 2013 Objects of the study were highly purified by liquid chromatography antibodies to DNA (IgG class) from the blood serums of healthy donors, patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), and clinically healthy relatives of RA patients. It has been shown that, depending on the pathology, these antibodies differ in the DNA-hydrolyzing activity and differently affect the number of viable cells, morphology and chromatin of MDCK cells after co-culture. The antibodies to DNA were located in the area of nuclei. Biological role of the antibodies to DNA is discussed.
23505234 IL-7 receptor α expressing B cells act proinflammatory in collagen-induced arthritis and 2014 Jan OBJECTIVES: The sympathetic nervous system (SNS) as well as the interleukin (IL)-7/IL-7 receptor (IL-7R) system play a role in the pathogenesis of arthritis. However, the target cells and mechanisms involved are not fully resolved. The goal of this study was to determine if B cells are influenced by IL-7 and to investigate the possible interplay between the SNS and the IL-7/IL-7R system on B cells in arthritis. METHODS: Collagen type II-induced arthritis (CIA) in DBA1 mice. ELISA to determine specific anti-CII antibodies. Fluorescence activated cell sorting (FACS) analysis to determine IL-7R+ cells and intracellular phosphorylated signal transducer and activator of transcription 5 (pSTAT5). Immunohistochemistry to show IL-7R+ B cells in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. RESULTS: IL-7 stimulated IL-7R+ mature B cells act proinflammatory (increased clinical score, increased anticollagen type II antibodies) after cell transfer in CIA. The sympathetic neurotransmitter norepinephrine abrogates this effect. Expression of IL-7Rα is increased when B cells are activated (anti-CD40 or lipopolysaccharide) in vitro and stimulating the IL-7R induces intracellular accumulation of pSTAT5. α- And β-adrenergic agonists show no influence on expression levels of IL-7R on activated B cells; however, intracellular IL-7R downstream signalling is abrogated via the β2-adreonceptor (β2AR) agonist terbutaline. IL-7R and β2AR are also expressed on B cells in synovial tissue from RA and OA patients. CONCLUSIONS: These data indicate that IL7R+ B cells have a proinflammatory role in arthritis which can be inhibited by the sympathetic neurotransmitter norepinephrine via inhibition of IL-7R signalling.
22447522 Serum amyloid A (SAA) induces pentraxin 3 (PTX3) production in rheumatoid synoviocytes. 2013 Jan OBJECTIVE: Pentraxin 3 (PTX3) is an acute-phase reactant that is involved in amplification of the inflammatory response and innate immunity. In the present study, we evaluated the relationship between PTX3 and serum amyloid A (SAA), another acute-phase reactant, in rheumatoid synoviocytes. METHODS: PTX3 mRNA expression was examined by reverse transcription polymerase chain reaction, and PTX3 protein was measured by enzyme-linked immunosorbent assay. RESULTS: SAA induced PTX3 mRNA and PTX3 protein expression in rheumatoid synoviocytes. SAA-induced PTX3 expression was attenuated when rheumatoid synoviocytes were nucleofected with N-formyl peptide receptor ligand-1 (FPRL-1)-specific siRNA, suggesting the involvement of FPRL-1. Furthermore, SAA-induced PTX3 expression was inhibited by NF-κB or mitogen-activated protein kinase-specific inhibitors. Neither soluble TNF receptor (etanercept) nor recombinant IL-1 receptor antagonist affected PTX3 production by SAA-stimulated synoviocytes, suggesting that SAA directly induces PTX3. CONCLUSION: Our data suggest that SAA plays a role in the proinflammatory and immune responses in rheumatoid synovium by inducing PTX3. We provide the first evidence that the acute-phase reactant SAA, which is produced systemically by hepatocytes, perpetuates the rheumatoid inflammatory processes by inducing another proinflammatory molecule, PTX3, locally in rheumatoid synovial tissues.
24202614 Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibi 2014 May Biological treatment with inhibitors of the pro-inflammatory cytokine TNF-alpha has dramatically improved the disease course of several chronic rheumatologic conditions. Adverse events (AEs) are primarily infections and hypersensitivity reactions. Demyelinizing neurological symptoms resembling multiple sclerosis (MS) have been described as a rare AE. During about 10-year use of anti TNF-alpha, the Danish Medicines Agency has recorded eight cases of MS like AEs. The objective of this study was to estimate the incidence of demyelinizing AEs both in the central and peripheral nervous system after treatment with anti TNF-alpha in a cohort of patients from a large rheumatologic outpatient clinic in Copenhagen. In a 4-year period from January 2008 to December 2011, approximately 550 patients annually were undergoing treatment with anti TNF-alpha inhibitors in our department. We collected data on all patients who developed neurological symptoms during this time period. We found six patients with signs of demyelinizing neurological disorders: four resembling MS, one MS-like condition, and one multifocal motor neuropathy. During a relatively short time period, we found a remarkably high number of neurological demyelinizing AEs probably linked to anti TNF-alpha treatment. The AEs were not associated with a single anti TNF-alpha agent and were thus presumably a class effect. The data presented suggest that neurological AEs may be underreported. We advocate that physicians handling patients during treatment with TNF inhibitors are aware of this potentially serious AE and report these events to the proper medical authorities.
24799765 Adipokines as potential biomarkers in rheumatoid arthritis. 2014 Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease characterized by severe joint injury. Recently, research has been focusing on the possible identification of predictor markers of disease onset and/or progression, of joint damage, and of therapeutic response. Recent findings have uncovered the role of white adipose tissue as a pleiotropic organ not only specialized in endocrine functions but also able to control multiple physiopathological processes, including inflammation. Adipokines are a family of soluble mediators secreted by white adipose tissue endowed with a wide spectrum of actions. This review will focus on the recent advances on the role of the adipokine network in the pathogenesis of RA. A particular attention will be devoted to the action of these proteins on RA effector cells, and on the possibility to use circulating levels of adipokines as potential biomarkers of disease activity and therapeutic response.
25270855 Prescriber preference for a particular tumour necrosis factor antagonist drug and treatmen 2014 Sep 30 OBJECTIVE: To assess the effect of physician preference for a particular tumour necrosis factor α (TNF) antagonist on the risk of treatment discontinuation in rheumatoid arthritis. DESIGN: Population-based cohort study. SETTING: British Columbia administrative health data (inpatients, outpatients and pharmacy). PARTICIPANTS: 2742 British Columbia residents who initiated a first course of a TNF antagonist between 2001 and December 2008, had been diagnosed with rheumatoid arthritis, and were treated by 1 of 58 medium-volume to high-volume prescribers. INDEPENDENT VARIABLE: A level of physician preference for the drug (higher or lower) was assigned based on preceding prescribing records of the care-providing physician. Higher preference was defined as at least 60% of TNF antagonist courses initiated in the preceding year. Sensitivity analysis was conducted with different thresholds for higher preference. MAIN OUTCOME MEASURE: Drug discontinuation was defined as a drug-free interval of 180 days or switching to another TNF antagonist, anakinra, rituximab or abatacept. The risk of discontinuation was compared between different levels of physician preference using survival analysis. RESULTS: Higher preference for the prescribed TNF antagonist was associated with improved persistence with the drug (4.28 years (95% CI 3.70 to 4.90) vs 3.27 (2.84 to 3.84), with log rank test p value of 0.017). The adjusted HR for discontinuation was significantly lower in courses of drugs with higher preference (0.85 (0.76 to 0.96)). The results were robust in a sensitivity analysis. CONCLUSIONS: Higher physician preference was associated with decreased risk of discontinuing TNF antagonists in patients with rheumatoid arthritis. This finding suggests that physicians who strongly prefer a specific treatment help their patients to stay on treatment for a longer duration. Similar research on other treatments is warranted.
23887286 Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthriti 2014 Oct OBJECTIVES: Accelerated cardiovascular morbidity and mortality occur in patients with rheumatoid arthritis (RA). We evaluated the presence, burden and compositional differences of coronary plaque in patients with RA without symptoms or diagnosis of coronary artery disease (CAD) compared against controls. METHODS: One hundred and fifty patients with RA and 150 matched controls underwent 64-slice CT angiography (CTA) for evaluation of coronary plaque. Numbers of segments with plaque per patient (Segment involvement score (SIS)), degree of segment stenosis (stenosis severity score (SSS)), plaque size (plaque burden score (PBS)), and composition were assessed using a standardised American Heart Association 15-segment model. Lesions were classified as non-calcified plaque (NCP), mixed (MP), and fully calcified plaque (CP). RESULTS:  Higher proportion of patients with RA had plaque when compared with controls (71% vs 45%, p<0.0001); 13.5% of total RA segments harboured plaque compared with 6% in controls (p<0.0001), and all plaque types were higher (p<0.001). Multivessel disease, both non-obstructive and obstructive, was more prevalent, and quantitative measures of stenotic plaque severity (SSS) and extent (PBS) were higher in RA, even after adjustments for cardiac risk factors (p<0.01 for all). A steeper progression of plaque with age was seen in RA. Disease activity associated only with presence of NCP and MP, whereas patient age was the only predictor of fully CP. CONCLUSIONS: RA patients without CAD have higher prevalence, extent, and severity of all types of coronary plaque. Residual disease activity associates with presence of higher risk NCP and MP potentially contributing to future adverse cardiac events.
22722918 Layilin, a talin-binding hyaluronan receptor, is expressed in human articular chondrocytes 2013 May OBJECTIVE: Layilin (LAYN), a 55-kDa transmembrane protein with homology to C-type lectins, has been identified as a receptor of hyaluronan (HA). Interestingly, LAYN does not share any sequence homology with CD44, a primary HA receptor. The primary aim of our study was to examine the expression and potential function of LAYN in human articular chondrocytes and synoviocytes. METHODS: Samples were obtained from patients undergoing joint arthroplasty. Cells were grown in vitro, then stimulated with interleukin (IL)-1β or tumor necrosis factor alpha (TNFα) for 24 h and the expression of LAYN was analyzed. To assess the function of LAYN, we transfected chondrocytes with siRNA against LAYN, treated them with HA and IL-1β, and then analyzed the production of matrix metalloproteinase (MMP)-1 and MMP-13 in the treated chrondrocytes. RESULTS: The results showed that LAYN was constitutively expressed in human articular chondrocytes and synoviocytes and that IL-1β significantly suppressed the expression of LAYN in these cells. HA repressed IL-1β-induced MMP-1 and MMP-13 production in chondrocytes, but this was significantly abrogated in chondrocytes transfected with siRNA against LAYN. CONCLUSIONS: Our results show that human chondrocytes express LAYN, a novel HA receptor, and that LAYN may contribute to the regulation of HA functions in the arthritic condition. Further investigation of the HA receptor may lead to the development of novel therapeutics to regulate HA signaling in inflammatory arthritis.
24099961 Tocilizumab in patients with active rheumatoid arthritis and inadequate response to diseas 2014 Mar OBJECTIVES: To analyze the Spanish experience in an international study which evaluated tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFis) in a clinical practice setting. MATERIAL AND METHODS: Subanalysis of 170 patients with RA from Spain who participated in a phase IIIb, open-label, international clinical trial. Patients presented inadequate response to DMARDs or TNFis. They received 8mg/kg of tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 20 weeks. Safety and efficacy of tocilizumab were analyzed. Special emphasis was placed on differences between failure to a DMARD or to a TNFi and the need to switch to tocilizumab with or without a washout period in patients who had previously received TNFi. RESULTS: The most common adverse events were infections (25%), increased total cholesterol (38%) and transaminases (15%). Five patients discontinued the study due to an adverse event. After six months of tocilizumab treatment, 71/50/30% of patients had ACR 20/50/70 responses, respectively. A higher proportion of TNFi-naive patients presented an ACR20 response: 76% compared to 64% in the TNFi group with previous washout and 66% in the TNFi group without previous washout. CONCLUSIONS: Safety results were consistent with previous results in patients with RA and an inadequate response to DMARDs or TNFis. Tocilizumab is more effective in patients who did not respond to conventional DMARDs than in patients who did not respond to TNFis.
25586354 [Exploration of risk factors on the occurrence of osteoporotic vertebral fracture in patie 2014 Nov OBJECTIVE: To explore the prevalence of osteoporosis (OP) and vertebral osteoporotic fracture (OPF) and related risk factors in patients with rheumatoid arthritis (RA). METHOD: A total of 644 patients with RA from Jan. 2010 to Oct. 2013 were recruited, anteroposterior and lateral X-rays examination of vertebral column (T5-L5) were conducted, and semi-quantity method were used as the standard for judging vertebral OPF. Meanwhile, patients' clinical and laboratory data including daily dosage of glucocorticoid, duration of glucocorticoid usage, cumulative amount dosage of glucocorticoid were recorded in details. 158 normal subjects were selected as control group. RESULTS: (1)The prevalence of vertebral OPF in patients with RA was 16.6%. Bone mineral density (BMD) of all measured lumbar vertebra in RA group were markedly decreased [(0.97 ± 0.22) g/cm(2)]. The total prevalence of OP at lumbar vertebra in RA was 17.9% (81/452), which was significantly higher than that of control group (4.4%, 7/158) (P < 0.001). (2) The percentage of OP in RA patients with vertebral OPF was significantly higher than that in patients without OPF [40.6% (41/101) vs 11.4% (40/351); P < 0.001]. Patients with OPF were of older age, longer use of glucocorticoid, more cumulative amount dosage of glucocorticoid, longer disease duration, higher scores of health assessment questionnaires (HAQ) and increased ESR (P < 0.05). (3) Logistic regression analysis revealed that age (OR = 1.094, 95% CI 1.065-1.125, P < 0.001) and gender (1 = male, 2 = female) (OR = 5.600, 95% CI 2.097-15.087, P = 0.001) were the risk factors for the development of OP in RA, while body mass index (BMI) was the protective factor (OR = 0.770, 95% CI 0.696-0.853, P < 0.001). Age (OR = 1.031, 95% CI 1.009-1.053, P = 0.005) and occurrence of OP at lumbar vertebra (OR = 3.765, 95% CI 2.092-6.776, P < 0.001) were risk factors of the development of OPF in RA patients. Logistic regression analysis also showed that RA was the risk factor of OPF (OR = 4.716, 95% CI 1.987-11.192, P < 0.001), even after the adjustment of age, gender and BMI. (4) Receiver operator characteristic(ROC) curve in RA patients with OPF has found that age-OPF and daily dosage of glucocorticoid-OPF AUCROC were 0.689 and 0.636 respectively. The cut-off value in ROC curve of age and daily dose or treatment course of glucocorticoid-OPF were 54.5 years and 6.25 mg (P < 0.001) , while duration of glucocorticoid usage-OPF AUCROC was 0.685, with cut-off value in ROC of age-OPF 135 days (P < 0.001). CONCLUSION: Prevalence of OPF in patients with RA increases remarkably. Old age and OP at spine are risk factors related to the development of OPF in patients with RA.