Abstract:
INTRODUCTION:UK guidelines recommend that all early active rheumatoid arthritis (RA) patients are offered combination disease-modifying antirheumatic drugs (DMARDs) and short-term corticosteroids. Anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA may differ in their treatment responses. We used data from a randomized controlled trial - the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial - to examine whether responses to intensive combination treatments in early RA differ by ACPA status. METHODS:The CARDERA trial randomized 467 early active RA patients to receive: (1) methotrexate, (2) methotrexate/ciclosporin, (3) methotrexate/prednisolone or (4) methotrexate/ciclosporin/prednisolone in a factorial-design. Patients were assessed every six months for two years. In this analysis we evaluated 431 patients with available ACPA status. To minimize multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline for each outcome (Larsen, disease activity scores on a 28-joint count (DAS28), Health Assessment Questionnaire (HAQ), EuroQol, SF-36 physical component summary (PCS) and mental component summary (MCS) scores). When a significant interaction was present, mean changes in outcomes were compared by treatment group at each time point using t-tests stratified by ACPA status. Odds ratios (ORs) for the onset of new erosions with treatment were calculated stratified by ACPA. RESULTS:ACPA status influenced the need for combination treatments to reduce radiological progression. ACPA-positive patients had significant reductions in Larsen score progression with all treatments. ACPA-positive patients receiving triple therapy had the greatest benefits: two-year mean Larsen score increases comprised 3.66 (95% confidence interval (CI) 2.27 to 5.05) with triple therapy and 9.58 (95% CI 6.76 to 12.39) with monotherapy; OR for new erosions with triple therapy versus monotherapy was 0.32 (95% CI 0.14 to 0.72; P = 0.003). ACPA-negative patients had minimal radiological progression irrespective of treatment. Corticosteroid's impact on improving DAS28/PCS scores was confined to ACPA-positive RA. CONCLUSIONS:ACPA status influences the need for combination DMARDs and high-dose tapering corticosteroids in early RA. In CARDERA, combination therapy was only required to prevent radiological progression in ACPA-positive patients; corticosteroids only provided significant disease activity and physical health improvements in ACPA-positive disease. This suggests ACPA is an important biomarker for guiding treatment decisions in early RA. TRIAL REGISTRATION:Current Controlled Trials ISRCTN32484878.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Seegobin SD,Ma MH,Dahanayake C,Cope AP,Scott DL,Lewis CM,Scott ICdoi
10.1186/ar4439subject
Has Abstractpub_date
2014-01-16 00:00:00pages
R13issue
1eissn
1478-6354issn
1478-6362pii
ar4439journal_volume
16pub_type
杂志文章,随机对照试验abstract:INTRODUCTION:The longitudinal degradation mechanism of extracellular matrix (ECM) in the interbertebral disc remains unclear. Our objective was to elucidate catabolic and anabolic gene expression profiles and their balances in intervertebral disc degeneration using a static compression model. METHODS:Forty-eight 12-we...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3764
更新日期:2012-03-06 00:00:00
abstract:BACKGROUND:To determine whether lung involvement is related to microvascular perturbations, nailfold videocapillaroscopy (NVC) was performed in patients with systemic sclerosis (SSc). METHODS:A cross-sectional study was consecutively accomplished in 152 SSc patients. NVC, a pulmonary function test and echocardiography...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1775-9
更新日期:2018-12-19 00:00:00
abstract::Inhibition of NF-kappaB is known to be effective in reducing both inflammation and bone destruction in animal models of arthritis. Our previous study demonstrated that a small cell-permeable NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), suppresses expression of proinflammatory cytokines and ameliorates ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2298
更新日期:2007-01-01 00:00:00
abstract::miRNAs have been shown to play essential regulatory roles in the innate immune system. They function at multiple levels to shape the innate immune response and maintain homeostasis by direct suppression of the expression of their target proteins, preferentially crucial signaling components and transcription factors. S...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4194
更新日期:2013-04-09 00:00:00
abstract:INTRODUCTION:The objective was to characterize the clinical and myopathologic features of patients with scleroderma-polymyositis (SSc-PM) overlap compared with a population of patients with systemic sclerosis (SSc) and polymyositis (PM). METHODS:A three-way comparison of patients with SSc-PM overlap (n = 25) with pati...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4562
更新日期:2014-05-13 00:00:00
abstract::The discovery of the receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) system and its role in the regulation of bone resorption exemplifies how both serendipity and a logic-based approach can identify factors that regulate cell function. Before this discovery in the mid to late 1990...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2165
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:The objective of this study was to examine the association between occupation and osteoarthritis (OA) leading to total knee (TKR) or hip (THR) joint replacement. METHODS:The following is the case-control study design. All patients still living in Iceland who had had a TKR or THR due to OA as of the end of...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3033
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Galactosylation of immunoglobulin G (IgG) is reduced in rheumatoid arthritis (RA) and assumed to correlate with inflammation and altered humoral immunity. IgG hypogalactosylation also increases with age. To investigate dependencies in more detail, we compared IgG hypogalactosylation between patients with RA,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1540-0
更新日期:2018-03-14 00:00:00
abstract:INTRODUCTION:Cardiovascular disease (CVD) is the leading cause of death in patients with inflammatory polyarthritis (IP), especially in seropositive disease. In established rheumatoid arthritis (RA), insulin resistance (IR) is increased and associated with CVD. We investigated factors associated with IR in an inception...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3476
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis is an autoimmune arthritis characterized by joint destruction. Anti-citrullinated protein antibodies are pathologic in rheumatoid arthritis, but the role of the citrullinated proteins themselves is much less clear. Citrullination is the conversion of the arginine residues of a protein ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4083
更新日期:2012-11-05 00:00:00
abstract::A dose-escalating phase II trial studied masitinib, an oral tyrosine kinase inhibitor, in 43 patients with rheumatoid arthritis. Masitinib induced American College of Rheumatology (ACR)20, ACR50 and ACR70 responses in 54%, 26% and 8% of patients, respectively. A placebo group was not included. Thirty-seven per cent of...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2734
更新日期:2009-01-01 00:00:00
abstract::The difficulty in predicting the consequences of interactions between different cytokine networks has increased with the expansion of the T helper (Th) cell universe and the discovery of numerous B lymphocyte-derived cytokines. Consequently, it is now difficult to conceptualize a straightforward view of the contributi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3348
更新日期:2011-07-06 00:00:00
abstract:INTRODUCTION:Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of a...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0814-z
更新日期:2015-10-22 00:00:00
abstract:INTRODUCTION:There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. MET...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2708
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Although rheumatoid arthritis (RA) is generally a chronic disease, a proportion of RA-patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission, reflecting loss of disease-persistence. To explore mechanisms underlying RA-persistence, we performed a candidate gene study. We hypo...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0739-6
更新日期:2015-09-08 00:00:00
abstract:INTRODUCTION:CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that is activated in the synovium in rheumatoid arthritis (RA) and promotes expression of various matrix metalloproteinases. In this study, we examined whether C/EBPβ mediates the expression of receptor activator of nuclear factor-kappa-B ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0532-6
更新日期:2015-02-17 00:00:00
abstract:INTRODUCTION:The purpose of this study was to examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA). METHODS:Serum levels of anti-cyclic citrullinated...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2945
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The high-affinity receptor for IgG Fcgamma/CD64 is critical for the development of lupus nephritis (LN). Cross-linking Fc receptor on recruited monocytes by IgG-containing immune complexes is a key step in immune-complex-mediated nephritis in systemic lupus erythematosus (SLE). The goal of this study was t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2590
更新日期:2009-01-01 00:00:00
abstract::The field of biomarkers is a growing one, particularly in osteoarthritis (OA). OA is the most common disabling condition in older persons and a major cause of morbidity. While the debate continues about which of the involved tissues--cartilage, bone or synovium--is the most important in OA aetiology, there is no doubt...
journal_title:Arthritis research & therapy
pub_type: 评论,社论,评审
doi:10.1186/ar2839
更新日期:2009-01-01 00:00:00
abstract::Synovial fluid from patients with various arthritides contains procoagulant, cell-derived microparticles. Here we studied whether synovial microparticles modulate the release of chemokines and cytokines by fibroblast-like synoviocytes (FLS). Microparticles, isolated from the synovial fluid of rheumatoid arthritis (RA)...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1706
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a r...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2765
更新日期:2009-01-01 00:00:00
abstract::Magnetic resonance imaging bone marrow edema is an imaging feature that has been described in many conditions, including osteomyelitis, overuse syndromes, avascular necrosis, trauma, and inflammatory arthritides. In rheumatoid arthritis (RA), bone edema has special significance as it has been shown to be a common and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4035
更新日期:2012-09-28 00:00:00
abstract:INTRODUCTION:The present study examined the effect of C-type natriuretic peptide (CNP) on the anabolic and catabolic activities in chondrocyte/agarose constructs subjected to dynamic compression. METHODS:Constructs were cultured under free-swelling conditions or subjected to dynamic compression with low (0.1 to 100 pM...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3459
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3205
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) patients have lower bone mineral density and increased fracture risk when compared with healthy individuals, due to distinct factors and mechanisms. Bone remodeling is a tightly orchestrated process dependent on several factors, including the balance between receptor acti...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/ar3500
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-2133-2
更新日期:2020-03-27 00:00:00
abstract:INTRODUCTION:This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort. METHODS:The magnitude of association for each genotype was assessed in 1,046 RA subjects...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2969
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2992
更新日期:2010-01-01 00:00:00
abstract::Prostaglandin E2 (PGE2) plays an important role in bone development and metabolism. To interfere therapeutically in the PGE2 pathway, however, knowledge about the involved enzymes (cyclooxygenases) and receptors (PGE2 receptors) is essential. We therefore examined the production of PGE2 in cultured growth plate chondr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1948
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relationship between autoantib...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1061-7
更新日期:2016-07-07 00:00:00