Abstract:
INTRODUCTION:Tumor necrosis factor (TNF) and, possibly, lymphotoxin alpha (LTα) signaling contribute to inflammation and rheumatoid arthritis (RA) pathogenesis. Pateclizumab (anti-lymphotoxin- alpha; MLTA3698A) is a humanized monoclonal antibody that blocks and depletes anti-LTα. This phase 2, randomized, head-to-head, active- and placebo-controlled trial examined the safety and efficacy of pateclizumab compared to adalimumab in RA patients with an inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). METHODS:Patients (n = 214) with active RA (≥ 6 swollen and tender joints, C-reactive protein ≥ 10 mg/L) on oral DMARDs were randomized (2:2:1) to receive pateclizumab 360 mg, adalimumab 40 mg, or placebo subcutaneously every 2 weeks. The primary endpoint, 4-variable, 28-joint disease activity score erythrocyte sedimentation rate (DAS28(4)-ESR) response, was evaluated at 12 weeks using an analysis of covariance (ANCOVA) model with adjustments for concomitant DMARD use and geographic region. Secondary efficacy endpoints included American College of Rheumatology (ACR) 20, ACR50, and ACR70 responses at Day 85. Pharmacokinetics, pharmacodynamics, and immunogenicity of pateclizumab were assessed. RESULTS:Pateclizumab reduced the DAS28(4)-ESR response (-1.89) at 12 weeks, however, this did not reach statistical significance compared to placebo (-1.54), while adalimumab (-2.52) differed significantly from both placebo and pateclizumab. Pateclizumab 12-week ACR20, ACR50 and ACR70 response rates (64%, 33%, and 14%) suggested clinical activity but were not statistically significant compared to placebo rates (46%, 24%, and 8%, respectively). CXCL13 serum levels decreased significantly following pateclizumab and adalimumab administration, demonstrating pharmacological target engagement by both drugs. Overall, adverse events (AEs) were comparable among all cohorts. Infections were the most common AE, occurring with comparable frequency in all groups. Serious AEs occurred in 0% of pateclizumab, 5.9% of adalimumab, and 2.3% of placebo patients, with serious infection in 2.3% of adalimumab patients and none in pateclizumab and placebo patients. CONCLUSIONS:Pateclizumab had a good safety profile in patients inadequately responsive to DMARDs, but no statistically significant improvement in RA signs and symptoms after 12 weeks of treatment. Adalimumab demonstrated efficacy and safety comparable to published results in this head-to-head comparison in DMARD-IR RA patients. TRIAL REGISTRATION:ClinicalTrials.gov NCT01225393, Registered 18 October 2010.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Kennedy WP,Simon JA,Offutt C,Horn P,Herman A,Townsend MJ,Tang MT,Grogan JL,Hsieh F,Davis JCdoi
10.1186/s13075-014-0467-3subject
Has Abstractpub_date
2014-10-30 00:00:00pages
467issue
5eissn
1478-6354issn
1478-6362pii
s13075-014-0467-3journal_volume
16pub_type
杂志文章,多中心研究,随机对照试验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:Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4368
更新日期:2013-01-01 00:00:00
abstract::In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1737
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The c-Jun N-terminal kinase (JNK) is a key regulator of matrix metalloproteinase (MMP) and cytokine production in rheumatoid arthritis (RA) and JNK deficiency markedly protects mice in animal models of arthritis. Cytokine-induced JNK activation is strictly dependent on the mitogen-activated protein kinase ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3750
更新日期:2012-02-21 00:00:00
abstract:BACKGROUND:Multisite pain and falls are common in older people, and isolated studies have identified multisite pain as a potential falls risk factor. This study aims to synthesise published literature to further explore the relationship between multisite pain and falls and to quantify associated risks. METHODS:Bibliog...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析
doi:10.1186/s13075-019-1847-5
更新日期:2019-02-22 00:00:00
abstract:BACKGROUND:The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor κB ligand (RANKL) blockade on severity of arthritis, bone destruction, an...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0931-3
更新日期:2016-01-23 00:00:00
abstract:BACKGROUND:Persistence of biologic therapy in psoriatic arthritis (PsA) patients is an important factor in individualized patient treatment planning and healthcare policy and guideline development. OBJECTIVE:To estimate the persistence of biologic agents prescribed to PsA patients in a real-life setting as well as fac...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-021-02417-x
更新日期:2021-01-29 00:00:00
abstract::Historically, the osteoblast has been considered the master cell in the control of osteoclast development and, therefore, bone resorption. Now the interactions between cells of the immune system and bone cells have redefined our thinking on the regulation of bone resorption. Moreover, the crosstalk between these cell ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2141
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was the evaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA). METHODS:Systemic and lo...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3090
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse. METHODS:The prooxidative, antiproliferative, and cytotoxic effects...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4351
更新日期:2013-10-28 00:00:00
abstract:BACKGROUND:Elevated B lymphocyte stimulator (BLyS) levels in patients with systemic lupus erythematosus (SLE) correlate positively with disease activity; BLyS expression is directly linked to interferon (IFN) pathway activation. This post hoc meta-analysis of BLISS-52 and BLISS-76 explored the relationship between base...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02177-0
更新日期:2020-05-04 00:00:00
abstract:BACKGROUND:Patient-reported outcomes measures, such as those provided by the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, have been found to be a reliable indicator of change during treatment, predictive of long-term outcomes, and the impact of psoriatic arthritis (PsA) on patients' lives. The objective...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02168-1
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:To investigate the association between blood biomarkers and disease activity of Takayasu's arteritis (TAK) in a follow-up cohort. METHODS:Disease activity was assessed by clinical manifestations and repeated vascular Doppler examinations. The association between erythrocyte sedimentation rate (ESR), serum l...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02365-y
更新日期:2020-12-10 00:00:00
abstract::The detection of autoantibodies in human sera is an important approach to the diagnosis and management of patients with autoimmune conditions. To meet market demands, manufacturers have developed a wide variety of easy to use and cost-effective diagnostic kits that are designed to detect a variety of human serum autoa...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar782
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and, consequently, enhances cell migration. Desp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02204-0
更新日期:2020-05-15 00:00:00
abstract::Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus. Evidence about its use was sought from full publications and abstracts of randomised trials and cohort studies by using a variety of search strategies. Effi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/ar2093
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:A proliferation-inducing ligand (APRIL) from the TNF family, owing to its role in the generation and survival of plasma cells (PCs), is currently targeted for rheumatoid arthritis (RA) treatment. However, little is known about APRIL expression in RA lesions, hampering our understanding of the way APRIL may...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2817
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Mutations in the NLRP3 gene are associated with the dominantly inherited cryopyrin-associated periodic syndrome (CAPS). The significance of the V198M variant is unclear; it has been reported in association with various CAPS phenotypes and as a variant of uncertain consequence. The aim of this study was to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4171
更新日期:2013-02-19 00:00:00
abstract::T-helper (Th) lymphocytes contribute to arthritis pathogenesis by helping B cells to produce antibodies, by producing cytokines that activate effector cells involved in the destruction of cartilage and bone, and by contributing to osteoclast differentiation. There are murine models of arthritis, most notably collagen-...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3008
更新日期:2010-01-01 00:00:00
abstract::Genomewide association studies (GWAS) have proven a powerful hypothesis-free method to identify common disease-associated variants. Even quite large GWAS, however, have only at best identified moderate proportions of the genetic variants contributing to disease heritability. To provide cost-effective genotyping of com...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3204
更新日期:2011-02-01 00:00:00
abstract:INTRODUCTION:Broad-range rDNA PCR provides an alternative, cultivation-independent approach for identifying bacterial DNA in reactive and other form of arthritis. The aim of this study was to use broad-range rDNA PCR targeting the 16S rRNA gene in patients with reactive and other forms of arthritis and to screen for th...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2748
更新日期:2009-01-01 00:00:00
abstract::One in six patients with systemic sclerosis will develop pulmonary arterial hypertension (PAH). Screening with echocardiography and possibly pulmonary function testing (to determine the diffusing capacity of carbon monoxide) is recommended to detect PAH at a less severe stage. However, real-world screening programs ha...
journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/s13075-017-1347-4
更新日期:2017-06-06 00:00:00
abstract:INTRODUCTION:TNFα is a proinflammatory cytokine that plays a central role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of certolizumab pegol, a TNFα blocker, on endothelial cell function and angiogenesis. METHODS:Human dermal microvascular endothelial cells (HMVECs) were stimulated wit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3812
更新日期:2012-04-25 00:00:00
abstract::There has been some evidence that Behçet's disease (BD) has a significant autoimmune component but the molecular identity of putative autoantigens has not been well characterized. In the initial analysis of the autoantibody profile in 39 Chinese BD patients, autoantibodies to cellular proteins were uncovered in 23% as...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1798
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS). ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3823
更新日期:2012-04-30 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate cau...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3759
更新日期:2012-01-01 00:00:00
abstract::Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8+ T cells in HLA-B27+-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodomin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1221
更新日期:2004-01-01 00:00:00
abstract::Antineutrophil antibodies are well recognized causes of neutropenia, producing both quantitative and qualitative defects in neutrophils and increased risk for infection. In primary autoimmune neutropenia (AIN) of infancy, a moderate to severe neutropenia is the sole abnormality; it is rarely associated with serious in...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1803
更新日期:2005-01-01 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:INTRODUCTION:Extracellular matrix (ECM) degradation leads to malfunction of the cartilage in osteoarthritis (OA). Inflammatory cytokine interleukin-1 beta (IL-1β) functions in ECM degradation and prevents ECM synthesis by down-regulating the key transcription factor, Sox9, and consequently inhibiting ECM gene expressio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4114
更新日期:2012-12-10 00:00:00