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ID PMID Title PublicationDate abstract
24432366 Poor knowledge of methotrexate associated with older age and limited English-language prof 2013 INTRODUCTION: Our objective was to determine rheumatoid arthritis (RA) patients' understanding of methotrexate and assess whether knowledge varies by age, education, English language proficiency, or other disease-related factors. METHODS: Adults with RA (n = 135) who were enrollees of an observational cohort completed a structured telephone interview in their preferred language between August 2007 and July 2009. All subjects who reported taking methotrexate were asked 11 questions about the medication in addition to demographics, education level, and language proficiency. Primary outcome was a total score below the 50th percentile (considered inadequate methotrexate knowledge). Bivariable and multivariable logistic regressions were performed. Covariates included demographics, language proficiency, education, and disease characteristics. RESULTS: Of 135 subjects, 83% were female, with a mean age of 55 ± 14 years. The majority spoke English (64%), followed by 22% Spanish and 14% Cantonese or Mandarin. Limited English language proficiency (LEP) was reported in 42%. Mean methotrexate knowledge score was 5.4 ± 2.6 (range, 0 to 10); 73 (54%) had a score lower than 5 (of 10). Age older than 55, less than high school education, LEP, better function, and biologic use were independently associated with poor knowledge. CONCLUSIONS: In a diverse RA cohort, overall methotrexate knowledge was poor. Older age and limited proficiency in English were significant correlates of poor knowledge. Identification of language barriers and improved clinician-patient communication around methotrexate dosing and side effects may lead to improved safety and enhanced benefits of this commonly used RA medication.
24380839 The role of LAIR-1 (CD305) in T cells and monocytes/macrophages in patients with rheumatoi 2014 Jan The LAIR-1 receptor is expressed on a majority of mononuclear leukocytes. It is used as a biomarker when testing synovial fluid for evidence of rheumatoid arthritis (RA). The primary objective of this study was to measure T cell- and monocyte/macrophage-specific LAIR-1 expression in RA patients and compare this to LAIR-1 expression in osteoarthritis (OA) patients and healthy individuals. LAIR-1 expression was significantly decreased in circulating CD4(+) T cells in RA patients compared to both OA patients and healthy individuals. In contrast, LAIR-1 is high in CD14(+) monocytes and local CD68(+) macrophages in synovial tissues from RA patients. Upon stimulation with TNF-α, LAIR-1 expression decreased in T-helper (Th)1 and Th2 CD4(+) T cells from healthy donors. These results indicate that LAIR-1 may exert different functions on T cells and monocytes/macrophages and suggest that LAIR-1 may be a novel therapeutic target for the treatment of RA.
23918589 A genome-wide association study reveals ARL15, a novel non-HLA susceptibility gene for rhe 2013 Dec OBJECTIVE: Genome-wide association studies (GWAS) and their subsequent meta-analyses have changed the landscape of genetics in rheumatoid arthritis (RA) by uncovering several novel genes. Such studies are heavily weighted by samples from Caucasian populations, but they explain only a small proportion of total heritability. Our previous studies in genetically distinct North Indian RA cohorts have demonstrated apparent allelic/genetic heterogeneity between North Indian and Western populations, warranting GWAS in non-European populations. We undertook this study to detect additional disease-associated loci that may be collectively important in the presence or absence of genes with a major effect. METHODS: High-quality genotypes for >600,000 single-nucleotide polymorphisms (SNPs) in 706 RA patients and 761 controls from North India were generated in the discovery stage. Twelve SNPs showing suggestive association (P < 5 × 10(-5)) were then tested in an independent cohort of 927 RA patients and 1,148 controls. Additional disease-associated loci were determined using support vector machine (SVM) analyses. Fine-mapping of novel loci was performed by using imputation. RESULTS: In addition to the expected association of the HLA locus with RA, we identified association with a novel intronic SNP of ARL15 (rs255758) on chromosome 5 (Pcombined = 6.57 × 10(-6); odds ratio 1.42). Genotype-phenotype correlation by assaying adiponectin levels demonstrated the functional significance of this novel gene in disease pathogenesis. SVM analysis confirmed this association along with that of a few more replication stage genes. CONCLUSION: In this first GWAS of RA among North Indians, ARL15 emerged as a novel genetic risk factor in addition to the classic HLA locus, which suggests that population-specific genetic loci as well as those shared between Asian and European populations contribute to RA etiology. Furthermore, our study reveals the potential of machine learning methods in unraveling gene-gene interactions using GWAS data.
23074131 Bisphosphonate use is associated with reduced risk of myocardial infarction in patients wi 2013 May Bisphosphonates have been shown to reduce mortality in patients with osteoporotic fractures, but the mechanism is unclear. Bisphosphonates have immunomodulatory effects that may influence the development of vascular disease. We sought to determine if bisphosphonate use is associated with a reduced risk of myocardial infarction (MI) in a rheumatoid arthritis (RA) population with high prevalence of bisphosphonate use and vascular disease. Adult patients with RA enrolled in the National Data Bank for Rheumatic Diseases, a longitudinal study of RA patients enrolled continuously from U.S. rheumatology practices between 2003 and 2011, were included in the analysis (n = 19,281). Patients completed questionnaires every 6 months. including questions on medication use, demographic information, clinical information, and health status. MIs were confirmed by a central adjudicator. Among the 5689 patients who were treated with bisphosphonates at some time during the study period, the risk of MI while on bisphosphonate compared to when not on bisphosphonate was 0.56 (95% confidence interval [CI], 0.37-0.86; p < 0.01) after adjustment for multiple confounders. In models including all 19,281 treated and untreated patients, the adjusted risk of first MI was 0.72 (95% CI, 0.54-0.96; p = 0.02) and of all MIs it was 0.72 (95% CI, 0.53-0.97; p = 0.03) in bisphosphonate users compared to nonusers. This finding suggests a potential mechanism for the mortality reduction observed with bisphosphonate medications.
24153347 Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism. 2013 Dec BACKGROUND: A low circulating vitamin B-6 concentration, which is an independent risk factor for cardiovascular disease, is commonly seen in human inflammation. OBJECTIVE: We investigated whether cyclooxygenase inhibitors alter vitamin B-6 metabolism. DESIGN: To investigate whether subjects taking a cyclooxygenase inhibitor had an altered vitamin B-6 profile, we conducted a cross-sectional study that involved 150 rheumatoid arthritis patients, with and without cyclooxygenase inhibitor treatments. C57BL/6J mice and hyperlipidemic Syrian hamsters received drug regimens that reflected clinical nonsteroidal antiinflammatory drug (NSAID) uses in treating human inflammation. The impact of long-term physiologic use of selective and nonselective cyclooxygenase inhibitors on vitamin B-6 metabolism was systematically investigated in these independent in vivo models. RESULTS: Patients who were taking cyclooxygenase inhibitors had lower circulating pyridoxal-5'-phosphate, especially those taking NSAIDs >6 mo. Long-term celecoxib and naproxen use reduced hepatic pyridoxal-5'-phosphate in mice. Nonselective cyclooxygenase inhibitor naproxen significantly decreased vitamin B-6 vitamers in the kidney. CONCLUSIONS: To our knowledge, we show novel findings that long-term physiologic doses of cyclooxygenase inhibitor may impede the synthesis of the coenzymatically active form of vitamin B-6. Because the cause of vitamin B-6 depletion in inflammation remains unknown, this study provides a potential mechanism that could account for the poor vitamin B-6 status in human inflammation. Moreover, this study further raises concerns about the long-term clinical use of antiinflammatory NSAIDs in humans. Vitamin B-6 status should be carefully monitored in long-term NSAID users. Future randomized placebo-controlled studies are needed to determine the impacts of antiinflammatory cyclooxygenase inhibitor use on vitamin B-6 metabolism in humans.
23687260 A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy an 2013 Oct OBJECTIVES: To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. METHODS: Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5-25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. RESULTS: At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI -6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28-CRP, ACR-EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. CONCLUSIONS: CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. CLINICALTRIALS.GOV IDENTIFIER: NCT01217086.
23497762 Budget impact modeling for a single-tablet formulation of ibuprofen and famotidine for pre 2013 Mar BACKGROUND: Single-tablet ibuprofen/famotidine is approved by the US Food and Drug Administration for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal (GI) ulcers in patients taking ibuprofen for those indications. Currently, little is known about the cost impact of gastroprotective therapies, and an estimate of the financial consequences of adopting these therapies will be helpful to decision makers. OBJECTIVES: The goal of this study was to review a model that evaluates the expected financial impact to US health care plans from the introduction of single-tablet ibuprofen/famotidine into the chronic NSAID user population. METHODS: A budget impact model, considering a typical health plan of 1 million enrollees, was used to compare patients receiving: (1) single-tablet ibuprofen/famotidine; (2) chronic NSAID treatment plus any GI-protective agent; and (3) chronic NSAID treatment without a GI-protective agent. RESULTS: The expected medication cost for single-tablet ibuprofen/famotidine was $734,192 ($81,577 in year 1, $244,731 in year 2, and $407,884 in year 3), corresponding to a total per-member per-month cost of $0.020 ($0.007 in year 1, $0.020 in year 2, and $0.034 in year 3). Considering anticipated decreases in the use of other NSAIDs, the use of GI-protective agents, and GI complications, the total expected 3-year drug cost for single-tablet ibuprofen/famotidine was offset by 50%, representing an estimated total budget impact of $364,396 or $0.010 per member per month. Sensitivity analyses of cost and market share variables and clinical and drug characteristics identified the most influential variables to be the cost of the drug and persistence to the ibuprofen/famotidine formulation, respectively. CONCLUSIONS: The expected decrease in treatment costs for less serious GI-related complications illustrates the benefits of single-tablet ibuprofen/famotidine as a gastroprotective therapy in patients receiving chronic NSAID treatment, with a modest financial impact on total health care costs.
24492460 TNF-α blockade induces IL-10 expression in human CD4+ T cells. 2014 IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.
24854356 What is the utility of routine ANA testing in predicting development of biological DMARD-i 2014 Sep OBJECTIVE: To determine whether serial ANA testing predicts biological disease modifying antirheumatic drugs (bDMARD)-associated ANA/dsDNA production in patients with rheumatoid arthritis (RA). METHODS: Serial autoantibody profiles, bDMARD treatment sequences and clinical data were collected from patients identified from our database that since 2005 received (i) a first bDMARD (tumour necrosis factor inhibitor (TNFi)) and (ii) tocilizumab and/or abatacept. RESULTS: Of over 1000 patients, 454 RA patients received a first TNFi. Infliximab group demonstrated higher ANA seroconversion rates (31.2%) compared with etanercept (11.8%) and adalimumab (16.1%) (p<0.001). Median (range) treatment duration prior to ANA seroconversion was 10.9 (1.3-80.0) months. Positive anti-dsDNA titres of IgG class (median (range) of 77 IU/mL (65-109)) were noted in six (7.2%) patients, within a median (range) of 2.0 (0.8-4.2) years. Three patients developed classifiable lupus. 4 of 74 (5.4%) primary non-responders and 24 of 111 (21.6%) secondary non-responders developed positive ANA antibodies after TNFi initiation (p=0.003). Seven (9.5%) tocilizumab-treated patients changed to positive ANA; five (8.6%) abatacept-treated patients changed to positive ANA status. CONCLUSIONS: This study demonstrates no utility of serial ANA/dsDNA testing that could be used to predict onset of seroconversion and therefore the development of lupus/vasculitis. An association however between seroconversion and the development of a secondary non-response to bDMARD therapy is suggested.
24697566 Meta-analysis of associations between the peroxisome proliferator-activated receptor-γ Pr 2014 May INTRODUCTION: The purpose of this study was to examine whether a Proline (Pro)-to-Alanine (Ala) exchange at codon 12 (Pro12Ala) polymorphism of the peroxisome proliferator-activated receptor-gamma (PPARγ) is associated with susceptibility to nonalcoholic fatty liver disease (NAFLD), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). METHODS: A meta-analysis was conducted on the association between the PPARγ Pro12Ala polymorphism and NAFLD, RA, and PsA. RESULTS: Nine studies, including five on NAFLD, two on RA, and two on PsA, were available for the meta-analysis consisting of 8082 cases and 3790 controls. The meta-analysis revealed no association between the Ala allele of the PPARγ Pro12Ala polymorphism and NAFLD (odds ratios [OR]=0.936, 95% confidence interval [CI]=0.672-1.302, p=0.693). However, stratification by ethnicity indicated an association between the Ala allele and NAFLD in East Asians (OR=0.700, 95% CI=0.496-0.987, p=0.042), but not in Europeans (OR=1.128, 95% CI=0.863-1.475, p=0.378). Analysis using the dominant model showed the same Ala allele pattern in East Asians and Europeans (OR=0.688, 95% CI=0.484-0.978, p=0.037; OR=1.051, 95% CI=0.782-1.413, p=0.742), demonstrating a significant association between the Ala allele and NAFLD in East Asians. The meta-analysis revealed no association between the Ala allele and RA in East Asians (OR=0.467, 95% CI=0.188-1.161, p=0.101), and no association was found between the Ala allele and PsA in Europeans (OR=0.869, 95% CI=0.465-1.627, p=0.662). CONCLUSIONS: Our meta-analysis demonstrates that the PPARγ Pro12Ala polymorphism is associated with susceptibility to NAFLD in East Asians, but not in European populations.
24786925 Longterm safety, efficacy, and inhibition of structural damage progression over 5 years of 2014 Jun OBJECTIVE: Evaluate the safety and efficacy of longterm abatacept (ABA) treatment over 5 years in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). METHODS: Patients from the 1-year, double-blind Abatacept in Inadequate Responders to Methotrexate (AIM) study (NCT00048568) received open-label ABA (∼10 mg/kg) in the longterm extension (LTE). Safety was assessed for patients who received ≥ 1 ABA dose, and efficacy for patients randomized to ABA and treated in the LTE. Radiographs were evaluated for changes in Genant-modified Sharp scores. RESULTS: Out of 652 patients, 539 entered the LTE (ABA, n = 378; placebo, n = 161). At Year 5, 72.4% were ongoing; discontinuation rates declined over time. Incidence rates of serious adverse events, serious infections, malignancies, and autoimmune events were 13.87, 2.84, 1.45, and 0.99 events/100 patient-years exposure, respectively. American College of Rheumatology 20 response was 82.3% (n = 373) and 83.6% (n = 268) at years 1 and 5, respectively. Disease Activity Score 28 C-reactive protein (DAS28-CRP) < 2.6 and ≤ 3.2 were achieved by 25.4% and 44.1% of patients at Year 1 (n = 370), and 33.7% and 54.7% at Year 5 (n = 267), respectively. Mean changes in DAS28-CRP and Health Assessment Questionnaire-Disability Index at Year 1 [-2.83 (n = 365) and -0.68 (n = 369)] were maintained at Year 5 [-3.14 (n = 264) and -0.77 (n = 271)] for patients continuing treatment. Of them, 59.5% (n = 291) and 45.1% (n = 235) remained free from radiographic progression at years 1 and 5, respectively. CONCLUSION: In MTX-refractory patients with RA, longterm ABA treatment was well tolerated and provided consistent safety and sustained efficacy, with high patient retention. Radiographic progression continued to be inhibited with ongoing treatment.
24096826 Activated protein C inhibits proliferation and tumor necrosis factor α-stimulated activat 2013 Oct 24 Synovial fibroblast proliferation is a hallmark of the invasive pannus in the rheumatoid joint. Activated protein C (APC) is a natural anticoagulant that exerts antiinflammatory and cyto-protective effects in various diseases via endothelial protein C receptor (EPCR) and proteinase-activated receptor (PAR)-mediated pathways. In this study, we investigated the effect and the underlying cellular signaling mechanisms of APC on proliferation of human rheumatoid synovial fibroblasts (RSFs). We found that APC stimulated proliferation of mouse dermal fibroblasts (MDFs) and normal human dermal fibroblasts (HDFs) by up to 60%, but robustly downregulated proliferation of RSFs. APC induced the phosphorylation of extracellular signal-regulated protein kinase (ERK) and enhanced expression of p21 and p27 in a dose-dependent manner in RSFs. The latter effect was inhibited by pre-treatment with the ERK inhibitors PD98059 and U0126 but not by p38 inhibitor SB203580. In addition, APC significantly downregulated tumor necrosis factor (TNF)α-stimulated cell proliferation and activation of p38, c-Jun NH2-terminal kinase (JNK) and Akt in RSFs. These results provide the first evidence that APC selectively inhibits proliferation and the inflammatory signaling pathways of RSFs. Thus, APC may reduce synovial hyperplasia and pannus invasion in rheumatoid arthritis.
25541410 Outcomes of coronary artery bypass grafting in patients with inflammatory rheumatic diseas 2015 Mar OBJECTIVE: Patients with inflammatory rheumatic diseases have an increased risk of developing coronary atherosclerosis. However, outcomes of surgical revascularization in these patients have been rarely studied. We aimed to determine whether, or which, inflammatory rheumatic diseases may pose effects on mortality and adverse cardiac outcomes after coronary artery bypass grafting. METHODS: By using the National Health Insurance Research Database of Taiwan, we identified 40,639 adult patients who underwent first-time coronary artery bypass grafting between 2000 and 2010. Among these patients, 101 had rheumatoid arthritis, 56 had systemic lupus erythematosus, and 73 had ankylosing spondylitis. The odds ratios (ORs) of operative mortality and hazard ratios (HRs) of overall mortality and adverse cardiac outcomes after coronary artery bypass grafting (ie, myocardial infarction and repeat revascularization) in relation to rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis were estimated. RESULTS: With adjustment for potential confounders including patient characteristics, hospital levels, and combined surgery, systemic lupus erythematosus was an independent predictor for operative mortality (adjusted OR, 2.63; 95% confidence interval [CI], 1.04-6.65; P = .04) and ankylosing spondylitis was marginally associated with operative mortality (adjusted OR, 2.41; 95% CI, 0.99-5.88; P = .054). Systemic lupus erythematosus was a significantly independent predictor for overall mortality during the follow-up period (adjusted HR, 2.23; 95% CI, 1.51-3.31; P < .0001) and might increase the risk of repeat revascularization (adjusted HR, 1.89; 95% CI, 0.97-3.68; P = .06). Neither rheumatoid arthritis nor ankylosing spondylitis was significantly associated with overall mortality and adverse cardiac outcomes. CONCLUSIONS: Our study may help surgeons and physicians recognize the potential risks inherent to systemic lupus erythematosus and ankylosing spondylitis when conducting coronary artery bypass grafting and providing follow-up care.
24729113 Metastatic bone lesion due to methotrexate and etanercept 24 years after breast cancer tre 2014 Apr 12 A 72-year-old woman with rheumatoid arthritis presented with lumbar vertebral bone metastasis 24 years after mammectomy and radiotherapy for breast cancer. She was treated with prednisolone and methotrexate (MTX) for 11 months to which 10 mg of etanercept twice a week was added for a further 8 months. On the basis of this result, the possibility of a metastatic bone lesion appearing many years after cancer treatment should be considered when planning MTX and etanercept therapy.
22994423 Development and psychometric testing of the Swedish version of the Body Awareness Question 2013 Jul AIM: This paper is a report of the development and psychometric testing of the Swedish version of the Body Awareness Questionnaire to measure bodily focus of attention. BACKGROUND: The Body Awareness Questionnaire has been identified as an instrument with excellent psychometric properties within the concept of body awareness. It has been used in both research and clinical settings in different contexts. However, a validated Swedish version is not available. METHOD: A cross-sectional design was applied for adaptation of the Body Awareness Questionnaire and psychometric validation. Data were collected between autumn 2009 and spring 2011 from 120 patients diagnosed with rheumatoid arthritis, and from 120 students. The 'concurrent think aloud' method was used in a pre-test to determine the usability of the questionnaire. Cronbach's alpha was used to test the internal consistency, and confirmatory factor analysis was performed to test the construct validity. RESULTS: According to the confirmatory factor analysis, neither the one-factor model nor the four-factor model tested in this study fulfilled the pre-specified criteria in accordance with the Comparative Fit Index, Standardized Root Mean Squared Residual and the Root Mean Square Error of Approximation. The value of Cronbach's alpha for the Swedish version of the Body Awareness Questionnaire was satisfactory. CONCLUSION: Our results indicate that the two models tested in this study do not provide a good fit to the observed data. Further refinement and testing of the Swedish version of the Body Awareness Questionnaire is therefore required. The concept of body awareness may be useful in the management of chronic disease and can be addressed in nursing.
24286242 IL-29 enhances Toll-like receptor-mediated IL-6 and IL-8 production by the synovial fibrob 2013 Oct 29 INTRODUCTION: We previously reported that IL-29, a newly described member of interferon (IFN) family, was overexpressed in blood and synovium of rheumatoid arthritis (RA) patients and triggered proinflammatory cytokine IL-6 and IL-8 mRNA expression in RA synovial fibroblasts (RA-FLS). This suggests that IL-29 has an important role in synovial inflammation. Toll-like receptors (TLRs) also activate RA-FLS to produce inflammatory mediators including tumor necrosis factor α (TNF-α) and IL-1β in RA-FLS. Since the TLR family plays an early role in the innate immune response and the subsequent induction of the adaptive immune response, we hypothesize that IL-29 interacts with TLRs in RA inflammation. This study aimed to investigate the effect of IL-29 on TLR-mediated proinflammatory cytokine production in RA-FLS. METHODS: The mRNA level of IL-29 receptors (IL-28Rα and IL-10R2) in RA-FLS was determined by semi-quantitative RT- PCR. IL-6 and IL-8 mRNA expressions in RA-FLS were evaluated by real-time PCR after pre-incubation with IL-29 and subsequent stimulation with peptidoglycan (PGN, TLR2 ligand), or polycytidylic acid (poly(I:C), TLR3 ligand), or lipopolysaccharide (LPS, TLR4 ligand) . The production of TLR2, 3, and 4 in RA-FLS after IL-29 stimulation was also assessed by real-time PCR and flow cytometry. IL-29 mRNA and protein expression in RA-FLS after stimulation with PGN, poly(I:C), or LPS were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: The IL-29 receptor complex (IL-28Rα and IL-10R2) was identified in RA-FLS. IL-29 enhanced TLR-mediated IL-6 and IL-8 expression in RA-FLS. IL-29 upregulated expression of TLR2, 3 and 4 in RA-FLS. Exposure to PGN, poly(I:C) or LPS triggered IL-29 production by RA-FLS. CONCLUSIONS: We show for the first time that IL-29 enhances TLR-induced proinflammatory cytokine production in RA-FLS via upregulation of TLRs.
25498771 Mapping from the Health Assessment Questionnaire to the EQ-5D: the impact of different alg 2014 Dec BACKGROUND: Many algorithms exist for converting the Health Assessment Questionnaire (HAQ) score to utility in rheumatoid arthritis (RA). Different algorithms convert the same HAQ score to different utility values, and could therefore lead to different cost-effectiveness results. OBJECTIVE: To investigate the impact of different mapping algorithms within the same cost-effectiveness model. METHODS: We rebuilt an existing economic model that had previously been used for estimating the cost-effectiveness of second-line biologics in RA. We reviewed the literature to identify algorithms that converted the HAQ score to utility and incorporated them into the model. We compared the cost-effectiveness results using different algorithms, exploring the reasons behind the different results and the potential effect on reimbursement decisions. RESULTS: We identified 24 different algorithms that estimated utility on the basis of the HAQ score, age, sex, and pain. The incremental cost-effectiveness ratio for rituximab versus disease-modifying antirheumatic drugs varied between £18,407/quality-adjusted life-year and £32,039/quality-adjusted life-year, which we speculate could have changed the recommendations made by the National Institute for Health and Care Excellence. CONCLUSIONS: Using different algorithms to convert the HAQ score to utility affects the cost-effectiveness of second-line biologics for the treatment of RA. Using different algorithms in economic modeling for RA could lead health technology assessment bodies to make different reimbursement decisions.
24595497 In vitro efficacy of polysaccharide-based nanoparticles containing disease-modifying antir 2014 Sep PURPOSE: To evaluate the therapeutic efficacy of dexamethasone (DM) and methotrexate (MTX) entrapped within polysialic acid (PSA)-trimethyl chitosan (TMC) nanoparticles using an in vitro model of rheumatoid arthritis (RA). METHODS: The loading capacity of the PSA-TMC nanoparticles was determined. An RA in vitro model was developed by stimulating a synovial cell line with a proinflammatory mediator. Multiplex immunoassay was used to determine changes in the secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by the in vitro model following administration of the DM- and MTX-loaded nanoparticles. RESULTS: The loading capacity of the PSA-TMC nanoparticles was approximately 0.1 mg of drug/mg of nanoparticle. When applied to our in vitro model of RA, there were no significant differences in the concentrations of IL-6 and IL-8 when comparing the free drugs and drug-loaded nanoparticles, administered at concentration of 0.1 mg/ml and 1.0 mg/ml, respectively. CONCLUSIONS: The present study verified that MTX and DM are able to retain bioactivity when loaded into PSA-TMC nanoparticles. Although in vitro efficacy was not increased, the in vivo efficacy will likely be enhanced by the site-specific targeting conferred by nanoparticle entrapment.
23658567 Seasonal disease activity and serum vitamin D levels in rheumatoid arthritis, ankylosing s 2013 Mar BACKGROUND: Vitamin D is a steroid hormone that plays essential roles in calcium and phosphorus metabolism, bone formation and mineralization homeostasis, also has a role in the maintenance of immune-homeostasis. OBJECTIVE: We aimed to investigate seasonal serum vitamin D levels and seasonal disease activity in patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Osteoarthritis. METHODS: Seventy-one Rheumatoid Arthritis patients, 72 Ankylosing Spondylitis patients, 74 knee Osteoarthritis patients and 70 healthy controls were recruited for the study. Bi-seasonal measurements of serum 25(OH)D vitamin were checked in either in July or August or September for summertime and either in December or January or February for wintertime. Disease activity were evaluated by Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index, and Western Ontario and McMaster Universities Osteoarthritis Index in groups of Rheumatoid Arthritis, Ankylosing Spondylitis, and Osteoarthritis respectively. RESULTS: We did not find any correlation between serum 25(OH)D levels and Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index, and Western Ontario and McMaster Universities Osteoarthritis Index scores in winter and summer. The difference of Disease Activity Score-28 and Western Ontario and McMaster Universities Osteoarthritis Index scores between winter and summer seasons were not significant in Rheumatoid Arthritis and Osteoarthritis patients (p>0.05). The mean Bath Ankylosing Spondylitis Disease Activity Index score was significantly higher in winter than in summer (p<0.05). Consequently we did not find any correlation between variations of seasonal serum 25(OH)D and the disease activity in the patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Osteoarthritis. CONCLUSION: These results suggest that vitamin D does not have an important role in the seasonal disease activity of these diseases and that seasonal changes in disease activity may play an important role in evaluating Ankylosing Spondylitis patients rather than Rheumatoid Arthritis and Osteoarthritis patients and should be taken into account when examining these patients. These conclusions need to be validated in multicenter studies with high number of patients.
24980417 Clinically important changes in short form 36 health survey scales for use in rheumatoid a 2014 Dec OBJECTIVE: Despite wide use of the Short-Form 36 (SF-36) health survey in clinical trials of rheumatoid arthritis (RA), estimates of minimum clinically important improvement (MCII) for its scales are not well-established. We estimated MCIIs for SF-36 scales in patients with active RA. METHODS: In this prospective longitudinal study, we studied 243 patients who had active RA and who completed the SF-36 before and after treatment escalation. We first assessed responsiveness with standardized response means (SRMs). For scales with adequate responsiveness (SRM ≥0.50), we used patient judgments of improvement in arthritis status as anchors for estimating MCIIs. We used receiver operating characteristic curve analysis to identify the MCIIs as the change associated with a specificity of 0.80 for improvement. RESULTS: Patients had substantial improvement in RA activity with treatment. However, among SF-36 scales, only the physical functioning and bodily pain scales and the physical component summary had adequate responsiveness. Using 0.80 specificity for improvement as the criterion, the MCIIs were 7.1 for the physical functioning scale, 4.9 for the bodily pain scale, and 7.2 for the physical component summary. CONCLUSION: Low responsiveness precluded estimation of valid MCIIs for many SF-36 scales in patients with RA, particularly the scales assessing mental health. Although the SF-36 has been included in many clinical trials to broaden the assessment of health status, low responsiveness limits the interpretation of changes in its mental health-related scales.