Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
26198030 The role of BAFF in the progression of rheumatoid arthritis. 2015 Dec Rheumatoid arthritis (RA) is a common autoimmune disease that is marked by a systemic inflammatory reaction and joint erosions. Elevated levels of B cell activating factor (BAFF) have been detected in the serum and synovial fluid of RA patients. Moreover, the levels of BAFF increase in cases of autoimmune disease and are correlated with the level of disease activity. As an innate cytokine mediator, BAFF affects the immune response of the synovial microenvironment. In this review, we consider recent observations of BAFF and its receptors in RA progression, as well as the effects of BAFF on the cell-cell interactions network. We also summarize the clinical development of BAFF antagonists for the treatment of RA.
26227164 Follicular helper T cells in rheumatoid arthritis. 2015 Sep Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in the joints and other tissues. Rheumatoid factor (RF) and anticyclic citrullinated peptides (anti-CCP) are biomarkers for the evaluation of RA although their functions in the pathogenesis of RA are poorly understood. CXC-chemokine receptor 5 (CXCR5)(+) T follicular helper (TFH) cells are essential for B cell maturation and antibody production. Recent studies have showed that dysregulated TFH cells are associated with the development of autoimmune diseases. This article reviews the characters and functions of TFH cells, such as their differentiation, expression, transcription factor, and B cell maturation. Meanwhile, we also discuss the possible mechanisms underlying the role of these cells in RA and potential treatments, including antibody-blocking agents, gene therapies, T cell vaccines, and T follicular regulatory (TFR) cells. Overall, we discuss the roles of TFH cells in the pathogenesis of RA and potential therapies for RA.
26473405 Amelioration of Experimental Autoimmune Arthritis Through Targeting of Synovial Fibroblast 2016 Feb OBJECTIVE: Synovial fibroblasts (SFs) with aberrant expression of microRNAs (miRNAs) are critical pathogenic regulators in rheumatoid arthritis (RA), and studies analyzing the effect of overexpressing or silencing miRNA expression in arthritis models can contribute to the development of miRNA-based therapeutic strategies. This study was undertaken to examine the hypothesis that miRNAs 140-3p and 140-5p are involved in the pathogenesis of RA, and to determine whether targeting SFs through the intraarticular (IA) delivery of these molecules could ameliorate autoimmune arthritis in mice. METHODS: Synovial tissue samples were obtained from patients with RA. In addition, 2 experimental models in mice were used, collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA). Overexpression of miRNAs 140-3p and 140-5p in SFs and synovial tissue was induced using lentivirus (LV)-mediated transfer of pre-miR-140 precursor molecules. RESULTS: Lower expression levels of miR-140-3p and miR-140-5p were detected in synovial tissue and SFs from patients with RA and from mice in both arthritis models. In mice with CIA and mice with CAIA, the LV-mediated IA transfer of miR-140-3p and miR-140-5p ameliorated arthritis, as determined by clinical examination and histopathologic evaluations showing a decrease in SF densities. Overexpression of miRNAs 140-3p and 140-5p caused a reduction in expression, with correlated kinetic patterns, of their corresponding target molecules sirtuin 1 and stromal cell-derived factor 1 in the SFs and joints of mice. Transfection of miR-140-3p and miR-140-5p into SFs increased cell apoptosis, reduced proliferation responses and migration abilities, and verified the concept that miR-140 expression is regulated by proinflammatory cytokines. CONCLUSION: These results demonstrate that targeting SFs by IA delivery of miRNAs 140-3p and 140-5p can ameliorate autoimmune arthritis. These findings might facilitate the pharmacologic development of molecular-based therapies in RA.
24913965 Antineutrophil cytoplasm antibody: positivity and clinical correlation. 2015 Jan OBJECTIVE: To determine positivity and clinical correlation of anti-neutrophil cytoplasmic antibodies (ANCA), taking into account the interference of antinuclear antibodies (ANA). MATERIAL AND METHODS: A prospective study was conducted in the Laboratory of Immunology of the National Cuban Center of Medical Genetic during one year. Two hounded sixty-seven patients with indication for ANCA determination were included. ANCA and ANA determinations with different cut off points and assays were determined by indirect immunofluorescense. Anti proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA. RESULTS: Most positivity for ANCA was seen in patients with ANCA associated, primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus erythematosus. Presence of ANCA without positivity for proteinase 3 and myeloperoxidase was higher in patients with ANA and little relation was observed between the perinuclear pattern confirmed in formalin and specificity by myeloperoxidase. Highest sensibility and specificity values for vasculitides diagnostic were achieved by ANCA determination using indirect immunofluorescense with a cut off 1/80 and confirming antigenic specificities with ELISA. CONCLUSION: ANCA can be present in a great number of chronic inflammatory or autoimmune disorders in the population studied. This determination using indirect immunofluorescence and following by ELISA had a great value for vasculitis diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin assay when ANA is present.
25310509 Vitamin D serum level, disease activity and functional ability in different rheumatic pati 2015 Jan BACKGROUND: The aim of the study was to determine the serum vitamin D levels in patients with psoriatic arthritis (PsA) and compare it with patients with rheumatoid arthritis (RA) and with osteoarthritis (OA), as well as to explore the relationship of the vitamin D level with indices of disease activity and functional ability in a real-life setting in a South-European country. METHODS: In a cross-sectional study, 120 adult patients with established diagnosis of PsA, RA and OA were consecutively enrolled. Serum 25-hydroxyvitamin D and intact parathyroid hormone were determined. Parameters of disease activity and functional ability were obtained using standard instruments. RESULTS: Serum vitamin D insufficiency (≤ 75 nmol/L) was found in 74% of patients with PsA, 94% patients with RA and 97% of patients with OA, whereas vitamin D deficiency (≤ 25 nmol/L) was found in 13% of patients with PsA, 39% of patients with RA and in 38% of patients with OA. Compared with RA, patients with PsA had significantly higher serum vitamin D (P = 0.002), and when controlling for age and gender, their serum vitamin D level was significantly associated with disease activity and functional activity. CONCLUSIONS: In the group of rheumatic patients, a high prevalence of serum vitamin D insufficiency/deficiency was found regardless of the type of arthritis. Patients with PsA might have higher levels of vitamin D than patients with RA, and this was associated with disease activity and functional ability. The results of this study indicate that prophylactic supplementation with vitamin D might be recommended for all rheumatic patients.
25639457 Clinical practice guidelines for the management of pregnancy in women with autoimmune rheu 2015 Sep BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphospholipid antibody syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and grading of recommendations, internal validation by peers, and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The various panels answered the 37 questions related to maternal and fetal care in SLE, RA, and APS, as well as to the use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. We present the recommendations for pregnant women with SLE in this first part. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with SLE integrate the best available evidence for the treatment and follow-up of patients with these conditions.
26278073 IL-29 Enhances LPS/TLR4-Mediated Inflammation in Rheumatoid Arthritis. 2015 BACKGROUND/AIMS: Interleukin-29 (IL-29), a critical member of type III interferons (IFNs) family, has been implicated in protecting against viral infection and modulating autoimmune inflammation. Toll-like receptor 4 (TLR4) plays a crucial role in synovial inflammation and may contribute to the pathogenesis of rheumatology arthritis (RA). However, little is known about the modifying effect of IL-29 on TLR4-mediated inflammation in RA. We aim to investigate the potential association between IL-29 and TLR4 in RA. METHODS: Peripheral blood mononuclear cells (PBMCs) and serum from 77 patients with RA and 70 controls were collected to determine levels of IL-29 and TLR4 mRNA by real-time polymerase chain reaction (PCR). Levels of IL-29 and TLR4 in synovial tissues and fluid from 25 RA patients and 24 controls were detected by enzyme-linked immunosorbent assay (ELISA) or western blot assay, respectively. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) and/or IL-29. The production of inflammatory cytokines including IL-6, IL-8 as well as TNF-α and the activation of nuclear factor-κB (NF-κB) signaling were determined. RESULTS: In comparison with controls, increased IL-29 was observed in PBMCs, synovial tissue, serum and synovial fluid of patients with RA. Besides, TLR4 was significantly elevated in PBMCs and synovium of RA patients. Moreover, IL-29 was positively associated with TLR4 in RA, suggested by Pearson's correlation analysis. When RAW264.7 cells were stimulated by LPS with or without IL-29 in vitro, IL-29 could enhance LPS-mediated TLR4 expression and the production of IL-6, IL-8 and TNF-α in RAW264.7 cells via the activation of NF-κB signaling. CONCLUSION: The present study suggests, for the first time, that IL-29 can aggravate LPS/TLR4-mediated inflammation in RA depending on NF-κB signaling activation.
27311176 [Citrullination and rheumatoid arthritis]. 2016 Jun Anti-citrullinated peptide antibody (ACPA) is detected in rheumatoid arthritis (RA)patients, and its clinical importance is established for RA diagnosis and as a prognosis marker. ACPA itself plays some roles in RA pathogenesis, such as promoting osteoclastogenesis. Citrullinated epitope-specific T cells also play an important role in RA pathogenesis and a recent study showed the clinical efficacy of tolerance induction of citrullinated epitopes for RA. As a source of citrullinated antigens, neutrophil extracellular traps (NETs)are supposed, because NETs contain a plenty of citrullinated histones. Peptidylarginine deiminase (PADI) 4 is one of the RA risk genes and associated with protein citrullinations. PADI4 plays a pivotal role in NETosis. And, we recently demonstrated its importance in arthritis by analyzing PADI4-deficient mice.
25145773 Exogenous IL-2 controls the balance in Th1, Th17, and Treg cell distribution in patients w 2015 Apr Interleukin-2 (IL-2) has been suggested to control Treg/Th17 balance. Recently, we reported a relationship of rheumatoid arthritis (RA) activity/progression with irreversible systemic Treg and Th1 defects including serum IL-2 shortage. Herein, we explore the role of in vitro stimulation with rIL-2 in the observed immune alterations reversal. Patients with stable or progressive RA were assigned to methotrexate (MTX) group or to TNF-alpha inhibitors (iTNF) group, respectively. Flow cytometric analyses were performed before and after 6 months of treatment. Circulating Th1, Th17, and Treg cells were determined before and after 72-h culture with anti-CD3 + rIL-2. Before therapy, 72-h stimulation restored recently observed phenotypic Th cell alterations, except for the enriched Th17 subset normalized as late as after therapy in all patients. Under 6-month therapy, anti-CD3 stimulation changed the Th cell distribution only in progressive RA; despite Th1 enrichment, it revealed Treg population defects, which were completely reversed by exogenous IL-2 added to the stimulating culture. Our paper shows that in aggressive RA patients exhibiting serum IL-2 shortage despite iTNF therapy, exogenous rIL-2 is capable of promoting Treg differentiation affected by chronic activation, thus supporting its use in the combined strategy of biologic treatment of the progressive form of RA.
27189724 Power Calculation of Multi-step Combined Principal Components with Applications to Genetic 2016 May 18 Principal component analysis (PCA) is a useful tool to identify important linear combination of correlated variables in multivariate analysis and has been applied to detect association between genetic variants and human complex diseases of interest. How to choose adequate number of principal components (PCs) to represent the original system in an optimal way is a key issue for PCA. Note that the traditional PCA, only using a few top PCs while discarding the other PCs, might significantly lose power in genetic association studies if all the PCs contain non-ignorable signals. In order to make full use of information from all PCs, Aschard and his colleagues have proposed a multi-step combined PCs method (named mCPC) recently, which performs well especially when several traits are highly correlated. However, the power superiority of mCPC has just been illustrated by simulation, while the theoretical power performance of mCPC has not been studied yet. In this work, we attempt to investigate theoretical properties of mCPC and further propose a novel and efficient strategy to combine PCs. Extensive simulation results confirm that the proposed method is more robust than existing procedures. A real data application to detect the association between gene TRAF1-C5 and rheumatoid arthritis further shows good performance of the proposed procedure.
26516896 Impact of Fatigue in Rheumatic Diseases in the Work Environment: A Qualitative Study. 2015 Oct 28 Fatigue is a symptom of arthritis that causes difficulty at work. An improved understanding of this symptom could assist its management in the work environment. The aim of this study was to explore people with rheumatic diseases' experiences of fatigue in work. A qualitative descriptive design was used with semi-structured interviews and a constant comparative method of data analysis. There were 18 participants, the majority of them female with Rheumatoid Arthritis (RA) and working full-time. Three themes were identified: "Impact of fatigue on work performance" with cognition, mood and physical abilities being the main difficulties reported. In the second theme "Disclosure at Work" participants discussed disclosing their disease to employers but reported a lack of understanding of fatigue from colleagues. The final theme "work-based fatigue management strategies" included cognitive strategies and energy management techniques, which were mainly self-taught. In this study, fatigue was reported to impact on many areas of work performance with limited understanding from colleagues and employers. Interventions from health professionals to assist with development of work-related self-management skills are required to assist with symptom management in the work place. Such interventions should include education to employers and colleagues on the nature of fatigue in Rheumatic diseases.
25592233 The number of circulating monocytes as biomarkers of the clinical response to methotrexate 2015 Jan 16 BACKGROUND: The aim of this work was to analyze the number and distribution of circulating monocytes, and of their CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, in treatment-naive patients with rheumatoid arthritis (RA), and to determine their value in predicting the clinical response to methotrexate (MTX) treatment. METHODS: This prospective work investigated the number of circulating monocytes, and the numbers of CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, in 52 untreated patients with RA before MTX treatment, and at 3 and 6 months into treatment, using flow cytometry. RESULTS: The absolute number of circulating monocytes, and the numbers of CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, were significantly higher in MTX non-responders than in responders and healthy controls before starting and throughout treatment. Responders showed normal numbers of monocytes, and of their subset cells, over the study period. The pre-treatment absolute number of circulating monocytes, and the numbers of CD14(+high)CD16(-) and CD14(+high)CD16(+) subset cells, were found to be predictive of the clinical response to MTX, with a sensitivity and specificity of >70% and >88%, respectively. CONCLUSIONS: Treatment-naive patients with RA showed an anomalous distribution of circulating monocyte subsets, and an anomalous number of cells in each subset. A higher pre-treatment number of circulating monocytes, and higher numbers of CD14(+high)CD16(-) and CD14(+high)CD16(+) subset cells, predict a reduced clinical response to MTX in untreated patients with RA.
26060322 Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and w 2015 Oct OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF. METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3. RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients. CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.
26927557 [Hypercoagulable state is associated with NF-kappa B activation and increased inflammatory 2016 Mar OBJECTIVE: To investigate the mechanism of hypercoagulable state based on nuclear factor κB (NF-κB) pathway in patients with rheumatoid arthritis (RA). METHODS: Thirty-five RA patients were enrolled as well as 20 healthy volunteers as a control group. Interleukin-10 (IL-10), IL-6, IL-4, IL-17, NF-κB activator 1 (Act1), p50, p65, IκBα, platelet activating factor (PAF), PAF-acetylhydrolase (PAF-AH) and anti-cyclic citrullinated peptide (CCP) were detected using ELISA. The number of platelet (PLT) was detected using Sysmex XT-2000i automated hematology analyzer. The levels of D-dimer (D-D), fibrinogen (FBG), thrombin time (TT), prothrombin time (PT), and partial thromboplastin time (APTT) were detected using Sysmex CA-1500 automatic coagulation analyzer. Erythrocyte sedimentation rate (ESR) was detected using Westergren method. C-reactive protein and rheumatoid factor (RF) were detected using Hitachi 7060 automatic biochemical analyzer. Meanwhile, the mRNA expressions of Act1, p65, p50, IκBα and IκB kinase α (IKKα) were detected using semi-quantitative reverse transcription PCR. The expressions of p65, p50 and IκBα proteins were examined using Western blotting. The correlations of the above indexes were analyzed by Spearman correlation test. RESULTS: Compared with the normal group, the levels of DD, FBG, PLT significantly increased in the peripheral blood of RA patients, TT decreased, while APTT and PT were not significantly changed. IL-4, IL-10 and PAF-AH were significantly reduced in the sera of RA patients, while IL-6, IL-17, Act1, p50, p65, IκBα, IKKα and PAF were significantly elevated. Spearman correlation analysis showed that coagulant and fibrinolytic indexes were significantly correlated with cytokines, NF-κB, activity indexes and clinical symptoms and signs. CONCLUSION: The hypercoagulable state is common in the peripheral blood of RA patients, and it is closely related to inflammatory factors, activity indexes and abnormal activation of NF-κB.
26715774 Activation of dickkopf-1 and focal adhesion kinase pathway by tumour necrosis factor α in 2016 May OBJECTIVE: The objective of this study was to investigate the roles of dickkopf-1 (DKK-1) and integrin-related focal adhesion kinase (FAK) by TNF-α on the migration of fibroblast-like synoviocytes (FLSs) in RA. METHODS: Wound scratch assays were performed to assess FLS migration. Western blotting was used to measure the levels of DKK-1, Wnt signalling molecules and FAK signalling molecules. Quantitative real-time PCR was used to measure the expression levels of DKK-1, integrin αv, laminin, fibronectin, E-cadherin, MMP-8 and MMP-13. The concentrations of DKK-1, TNF-α and GSK-3β were measured by ELISA. Genetic silencing of TNF-α was achieved by the transfection of small interfering RNA into cells. RESULTS: Migrating RA FLSs exhibited higher levels of DKK-1 and TNF-α expression compared with those in OA FLSs and/or stationary RA FLSs. Moreover, migrating FLSs exhibited significantly higher levels of FAK, p-JNK, paxillin and cdc42 expression, whereas the level of cytosolic β-catenin was lower. WAY-262611, Wnt pathway agonist via inhibition of DKK-1, markedly inhibited cell migration of RA FLSs through the accumulation of cytosolic β-catenin and suppression of FAK-related signalling pathways. TNF-α treatment to RA FLSs up-regulated expression of DKK-1, integrin αv, fibronectin, laminin and MMP-13. TNF-α stimulation also suppressed cytosolic β-catenin and E-cadherin expression in a time-dependent manner. Moreover, TNF-α small interfering RNA-transfected migrating FLSs exhibited decreased activation of integrin-related FAK, paxillin, p-JNK and cdc42 signalling pathways. CONCLUSION: This study demonstrates that the activation of DKK-1 and the integrin-related FAK signalling pathway stimulated by TNF-α induces the dissociation of β-catenin/E-cadherin, thus promoting RA FLS migration.
24448344 Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibil 2015 Mar OBJECTIVE: To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the rheumatoid arthritis (RA) genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. METHODS: We analysed a total of 11,715 RA cases and 26,493 controls from nine independent cohorts; all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on osteopontin (OPN) expression in macrophages and OPN serum levels was investigated. RESULTS: We provide evidence for a distinct contribution of SPP1 to RA susceptibility according to ACPA status: the combination of ≥3 SPP1 rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (p=1.29×10(-5), ORACPA-negative 1.257 (1.135 to 1.394)) and less with ACPA positivity (p=0.0148, ORACPA-positive 1.072 (1.014 to 1.134)). The ORs between these subgroups (ie, ACPA-positive and ACPA-negative) significantly differed (p=7.33×10(-3)). Expression quantitative trait locus analysis revealed an association of the SPP1 risk-allele combination with decreased SPP1 expression in peripheral macrophages from 599 individuals. To corroborate these findings, we found an association of the SPP1 risk-allele combination and low serum level of secreted OPN (p=0.0157), as well as serum level of secreted OPN correlated positively with ACPA production (p=0.005; r=0.483). CONCLUSIONS: We demonstrate a significant contribution of the combination of SPP1 rs11439060 and rs9138 frequent alleles to risk of RA, the magnitude of the association being greater in patients negative for ACPAs.
27118330 [IL-6 blockade therapy for inflammatory diseases: current perspectives and future directio 2015 Interleukin-6 (IL-6) is a prototypical cytokine featuring pleiotropic and redundant activity. It is an essential factor to protect host from environmental stress and to maintain homeostasis, whereas its dysregulated, excessive or persistent production plays a pathological role in various inflammatory diseases. Then, IL-6 blockade was expected to become a novel therapeutic strategy and a humanized anti-IL-6 receptor antibody, tocilizumab was developed. Indeed, through clinical trials its efficacy and tolerable safety was proved and is now in clinical use for the treatment of chronic inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis and Castleman's disease. Moreover, ongoing various clinical studies suggest that it will be widely applicable for the treatment of intractable chronic immune-mediated diseases as well as acute severe inflammatory diseases presenting with "cytokine storm".
27422892 Effect of Adherence to Protocolized Targeted Intensifications of Disease-modifying Antirhe 2016 Sep OBJECTIVE: To investigate the association between adherence to treat-to-target (T2T) protocol and disease activity, functional outcomes, and radiographic outcomes in early rheumatoid arthritis (RA). METHODS: Data from a longitudinal cohort of patients with early RA were used. Adherence was determined at each followup visit over 3 years according to predefined criteria. The primary endpoint was remission according to Disease Activity Score in 28 joints (DAS28) and Simplified Disease Activity Index (SDAI) criteria. Functional and radiographic outcomes measured by modified Health Assessment Questionnaire and modified total Sharp score, respectively, were secondary endpoints. RESULTS: A total of 198 patients with 3078 clinic visits over 3 years were included in this analysis. After adjusting for relevant variables, although there was no significant association between adherence to T2T and remission rate after 1 year, the associations reached significance after 3 years for both DAS28 (OR 1.71, 95% CI 1.16-2.50; p = 0.006) and SDAI criteria (OR 1.94, 95% CI 1.06-3.56; p = 0.033). After 3 years, adherence was also associated with improvement in physical function (β=0.12, 95% CI 0.06-0.18; p < 0.0001). None of the radiographic outcomes were associated with adherence after either 1 or 3 years, although there was a trend for higher adherence to be associated with less radiographic progression at the end of the study (p = 0.061). CONCLUSION: Increased adherence to T2T was associated with better longterm disease activity and functional outcomes, which suggests that the benefit of a T2T protocol may be enhanced by ensuring adequate adherence.
25869348 Promotion of health-enhancing physical activity in rheumatoid arthritis: a comparative stu 2015 Oct The objectives of this study were to compare attitudes, practice of advice, perceived competencies and educational needs related to health-enhancing physical activity (HEPA) in rheumatoid arthritis (RA) among Dutch, Italian and Swedish healthcare providers (HCP) and to explore associations between these factors and age, gender and HEPA levels of HCP. Questionnaires were sent to 2939 HCP, members of their national rheumatology organizations. HEPA was assessed with the Short Questionnaire to Assess Health-Enhancing Physical Activity or the International Physical Activity Questionnaire; attitudes, practice of advice, perceived competencies and educational needs with a 23-item questionnaire. Overall response rate was 33 %. Ninety-five percent of HCP agreed that HEPA is an important health goal in RA. More Swedish HCP had positive attitudes to the attainability and safety of HEPA in RA. There were no differences between countries in practice of advice on HEPA to patients with RA in general or to those with recent onset disease, but more Italian HCP were reluctant to advise HEPA to patients with established disease. Of the total HCP, 36 to 60 % used public health guidelines to advise on HEPA, with Dutch HCP taking less advantage. Still they estimated a higher proportion of patients with RA to follow such advice. Italian HCP perceived their competencies the highest, but were also more interested in education to promote HEPA. Gender, age and HEPA performance had no association with attitudes toward HEPA, while a number of associations were found between these factors and practice of advice and perceived competencies. The differences found between HCP in the three countries might indicate the need for educational initiatives to improve HEPA promotion.
26899313 Examining Time to Initiation of Biologic Disease-modifying Antirheumatic Drugs and Medicat 2016 Mar PURPOSE: Little is known about the transition from nonbiologic disease-modifying antirheumatic drugs (DMARDs) to biologic DMARDs or about individual nonbiologic DMARD use patterns among patients with rheumatoid arthritis (RA). This study examined time to initiation of biologic DMARDs and nonbiologic DMARD medication adherence and persistence among Texas Medicaid recipients with RA taking nonbiologic DMARDs. METHODS: In this retrospective study (July 1, 2003-December 31, 2010) of the Texas Medicaid database, patients were aged 18 to 62 years at index, were diagnosed with RA (International Classification of Diseases, Ninth Revision, Clinical Modification, code 714.xx), had no claims for nonbiologic or biologic DMARDs in the preindex period, and had a minimum of 2 prescription claims for the same nonbiologic DMARD in the postindex period. Kaplan-Meier survival analysis and log-rank tests were used to compare time to initiation of biologic DMARDs according to nonbiologic DMARD type and therapy. Adherence and persistence were examined according to nonbiologic type and therapy by using ANOVA models and χ(2), Duncan, and t tests. FINDINGS: On average, patients were 47.9 (± 10.4) years of age, mostly female (89.1%) and Hispanic (55.2%). Methotrexate (MTX) and leflunomide (LEF) users took the shortest time to initiate biologic DMARDs (207 [190] days and 188 [205] days, respectively). LEF users had the highest mean adherence of 37.5% (27.5%), which was similar to MTX users (35.7% [26.9%]), whereas dual-therapy users had the lowest mean adherence at 17.1% (14.4%). Sulfasalazine users (108 [121] days) had the lowest persistence, whereas LEF (227 [231] days) and MTX (211 [222] days) users had the longest persistence. Nonbiologic DMARD monotherapy users were more adherent than dual-therapy users (32.6% [25.8%] vs 17.1% [14.4%]). IMPLICATIONS: These results should be interpreted in light of some study limitations, such as using proportion of days covered as a proxy for adherence, not having clinical data to control for RA severity, and lack of generalizability to all US populations. Given the study findings, both clinicians and other decision makers may want to investigate the potential driving factors of initiation of biologic DMARDs to provide effective RA management and consider patient education programs to enhance medication adherence and persistence to RA medications.