Abstract:
OBJECTIVE:To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc). METHODS:In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly for safety assessments. Modified Rodnan skin scores (MRSS) were assessed every 3 months. Pulmonary function testing, chest radiography, echocardiography and skin biopsies were performed at baseline and after 12 months of treatment. RESULTS:Twenty-four patients completed 12 months of therapy. 171 adverse events (AE) with possible relation to imatinib were identified; 97.6% were grade 1 or 2. Twenty-four serious AE were identified, two of which were attributed to study medication. MRSS decreased by 6.6 points or 22.4% at 12 months (p=0.001). This change was evident starting at the 6-month time point (Δ=-4.5; p<0.001) and was seen in patients with both early and late-stage disease. Forced vital capacity (FVC) improved by 6.4% predicted (p=0.008), and the diffusion capacity remained stable. The improvement in FVC was significantly greater in patients without interstitial lung disease. Health-related quality of life measures improved or remained stable. Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology. CONCLUSIONS:Treatment with imatinib was tolerated by most patients in this cohort. Although AE were common, most were mild to moderate. In this open-label experience, improvements in skin thickening and FVC were observed. Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind randomised placebo controlled trial is warranted. ClinicalTrials.gov, NCT00555581.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Spiera RF,Gordon JK,Mersten JN,Magro CM,Mehta M,Wildman HF,Kloiber S,Kirou KA,Lyman S,Crow MKdoi
10.1136/ard.2010.143974subject
Has Abstractpub_date
2011-06-01 00:00:00pages
1003-9issue
6eissn
0003-4967issn
1468-2060pii
ard.2010.143974journal_volume
70pub_type
杂志文章abstract:OBJECTIVE:To measure gelatinase activities in paired synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to assess how these activities relate to clinical and laboratory measures of disease activity. METHODS:A quantitative protein substrate zymography method was adapted and validate...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.039032
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:To evaluate the role of interleukin 6 (IL-6) in the pathogenesis of bilateral erosive sacroiliitis in human tumour necrosis factor transgenic (hTNFtg) mice, an animal model of ankylosing spondylitis (AS). METHODS:Histological sections of the sacroiliac joints from hTNFtg and IL-6(-/-)hTNFtg mice were evaluat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.129148
更新日期:2010-07-01 00:00:00
abstract::Pulsed methylprednisolone (PMP) has been shown to produce clinical improvement and reduction in the ESR and acute phase protein concentrations in patients with active rheumatoid arthritis and has been advocated for use either as an alternative to slow-acting antirheumatoid drugs (SAARDs) or in conjunction with SAARDs ...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/ard.44.11.747
更新日期:1985-11-01 00:00:00
abstract:OBJECTIVE:To study the ability of low-cost low-field dedicated extremity magnetic resonance imaging (E-MRI) to assess and predict erosive joint damage in the wrist and metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis. METHODS:24 previously untreated patients with rheumatoid arthritis with j...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2005.049213
更新日期:2006-09-01 00:00:00
abstract:OBJECTIVE:To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFalpha expression in the synovium before initiation of treatment. METHODS:Prior to initiation of infliximab treatment, arthroscopic synovial tissue...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.080440
更新日期:2008-08-01 00:00:00
abstract::Cultures of synovial cells obtained at surgery from patients with rheumatoid arthritis produced a protein which inhibits the mitosis of normal rabbit and human synovial cells, and of human lung fibroblasts. This mitotic inhibitory effect can be transferred to rabbit synovial cells by intra-articular injection of the a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.2.187
更新日期:1978-04-01 00:00:00
abstract:OBJECTIVE:To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2009.115535
更新日期:2010-05-01 00:00:00
abstract::Sixty six patients with systemic lupus erythematosus (SLE) were genotyped using a HindIII restriction fragment length polymorphism identified by CR1.1 cDNA, then were followed up for an average of 50 months to evaluate the stability of their CR1 activities. The gene frequencies for the two alleles which correlate with...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.50.11.765
更新日期:1991-11-01 00:00:00
abstract:OBJECTIVE:To identify potential risk factors for the onset of inflammatory arthritis (IA) in a large cohort of patients with psoriatic arthritis (PsA) of recent onset. METHODS:We recruited cases with psoriasis and an onset of IA within the past 5 years. Controls were patients who had psoriasis but no arthritis. We ass...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.073932
更新日期:2008-05-01 00:00:00
abstract:OBJECTIVES:To assess the association of body mass index (BMI) with modifiable cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). METHODS:BMI, disease activity, selected CVD risk factors and CVD medication were assessed in 378 (276 women) patients with RA. Patients exceeding accepted ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.095596
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVE:Etanercept monotherapy has been studied and approved for treatment of polyarticular juvenile idiopathic arthritis (JIA). The following study evaluates the safety and efficacy of combination therapy of etanercept and methotrexate compared to etanercept monotherapy in JIA. METHODS:We perfomed an open, non-rand...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1136/ard.2007.087593
更新日期:2009-04-01 00:00:00
abstract::The case is described of a patient with scleromyxoedema with features typical of systemic sclerosis. The features were so characteristic that the disease was misdiagnosed as systemic sclerosis. A brief review of the association of the two diseases is given. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.10.1159
更新日期:1992-10-01 00:00:00
abstract:BACKGROUND:Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. OBJECTIVE:To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab, adalimumab and etanercept, and the effect of immunosuppression on ADA detection, in patients with Rheumatoid Arthritis, Spondyloarthritis, P...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1136/annrheumdis-2012-202220
更新日期:2013-12-01 00:00:00
abstract:OBJECTIVES:To define pulmonary involvement on high resolution computed tomography (HRCT) of the thorax in lifelong non-smoking rheumatoid arthritis patients and to relate the results to pulmonary function, bronchial reactivity, and a variety of clinical and serological factors. METHODS:Twenty lifelong non-smoking RA p...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.4.308
更新日期:1995-04-01 00:00:00
abstract::This review focuses on the contribution of genetic markers to the severity of radiological damage in rheumatoid arthritis (RA). Currently available biomarkers of more severe disease include elevated erythrocyte sedimentation rates or C-reactive protein levels and rheumatoid factor (RF) or anticyclic citrullinated prot...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2009.117721
更新日期:2010-03-01 00:00:00
abstract::Plasma DNA has been measured by a new physiochemical approach based on fluorimetric analysis of phenol extracted nucleic acids electrophoresed on polyacrylamide gels. This method is specific for native double-stranded DNA of molecular weight greater than 5 x 10(6). The use of plasma rigorously freed of leucocytes is e...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.40.6.593
更新日期:1981-12-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that high concentrations of extracellular inorganic pyrophosphate (PPi), which associate with increased cell synthesis and turnover in cartilage, may act as a marker for structural outcome in knee osteoarthritis (OA). METHOD:One hundred and thirty five consecutive patients referred to ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.55.7.432
更新日期:1996-07-01 00:00:00
abstract:BACKGROUND:There is emerging evidence that the development and progression of osteoarthritis (OA) is associated with inflammation. C reactive protein (CRP), a systemic marker for inflammation, may be elevated in OA patients but the evidence is conflicting. OBJECTIVE:To systematically review the literature for the rela...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1136/annrheumdis-2013-204494
更新日期:2015-04-01 00:00:00
abstract::The biochemical evidence against incorporation of the purine analogues, allopurinol and oxipurinol, into nucleic acids is reviewed. Cytological experiments have been carried out to investigate the possibility that chromosomal damage might result from exposure of human lymphocytes to these drugs. Lymphocytes from 19 pa...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.35.2.143
更新日期:1976-04-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon gamma (IFNgamma), interleukin 4 (IL4), tumour necrosis factor alpha (TNFalpha), and IL10 at the single cell level in patients with AS in comparison with healthy HL...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.1.36
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Hand exercises are recommended for patients with hand osteoarthritis (HOA), though evidence for their effect is conflicting. OBJECTIVE:To evaluate, in a randomised controlled trial, the effect of HOA information plus home-based hand exercises (exercise group) compared with information only (control group) i...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2013-204808
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVE:Juvenile idiopathic arthritis (JIA) consists of a heterogeneous group of inflammatory disorders, within which there are a number of clinical subgroups. Diagnosis and assignment to a particular subgroup can be problematical and more concise methods of subgroup classification are required. This study of the syn...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.148635
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVE:Spondyloarthritis is a group of articular disorders sharing a genetic background. Polymorphisms in the IL-1 gene cluster have previously been associated with ankylosing spondylitis (AS), a subset of spondyloarthritis. This study examined the association between several of these polymorphisms and the whole spo...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200439
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVE:To develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice. METHODS:Candidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi surv...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-208671
更新日期:2016-06-01 00:00:00
abstract::The radiological development from normal bone of geodes and subsequent fractures in phalanges of two adjacent fingers is described in a patient with classical rheumatoid arthritis. Presentation was as a septic, discharging focus, but infection was excluded; the pathology is described. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.2.130
更新日期:1985-02-01 00:00:00
abstract:OBJECTIVES:The objectives of this study were to determine whether late apoptotic cell material directly induces autoantibodies characteristic of systemic lupus erythematosus (SLE) and to investigate the innate recognition pathways involved. METHODS:B6, B6.MyD88(-/-), B6.TLR7(-/-) and B6.TLR9(-/-) mice were subcutaneou...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.108282
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND:Earlier publications have suggested a possible role for the efflux transporter breast cancer resistance protein (BCRP) in acquired resistance to disease-modifying antirheumatic drugs (DMARDs) such as leflunomide and its metabolite A771726 (teriflunomide). However, there is no direct evidence that BCRP intera...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.086264
更新日期:2009-07-01 00:00:00
abstract::A previously normal 58-year-old woman developed a widespread psoriatic rash and asymmetrical peripheral polyarthritis a week after beginning treatment with oxprenolol for hypertension. Skin and joint disease resolved simultaneously after drug withdrawal and have not recurred. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.1.102
更新日期:1984-02-01 00:00:00
abstract:OBJECTIVES:Systemic lupus erythematosus (SLE) is a serious multisystem autoimmune disease, mediated by disrupted B cell quiescence and typically treated with glucocorticoids. We studied whether B cells in SLE are regulated by the glucocorticoid-induced leucine zipper (GILZ) protein, an endogenous mediator of anti-infla...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-207744
更新日期:2016-04-01 00:00:00
abstract::In a double blind, single observer, 48 week study the effects of sulphasalazine (2 g daily) and hydroxychloroquine (400 mg daily months 0-6, thereafter 200 mg daily) were compared in 60 patients with definite or classical rheumatoid arthritis. They had not been treated previously with second line drugs. The onset of r...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.48.5.389
更新日期:1989-05-01 00:00:00