Abstract:
BACKGROUND:Treatment with tumour necrosis factor inhibitors (TNF-i) plus methotrexate (MTX), but not MTX monotherapy alone, inhibits joint damage progression even at higher levels of disease activity. Such disassociation of disease activity and structural damage has not been shown for biological agents other than TNF-i. OBJECTIVES:To evaluate whether interleukin 6 (IL-6) inhibition with tocilizumab (TCZ) interferes with joint destruction beyond its effects on disease activity. METHODS:A random 90% sample of data from the (The Tocilizumab Safety and the Prevention of Structural Joint Damage Study) LITHE trial on active rheumatoid arthritis (RA) despite MTX was used, which compared addition of placebo (n=117) with addition of TCZ (n=414) every 4 weeks. Baseline and 1-year values of clinical and serological variables were correlated with changes to 1 year of the total Genant-modified Sharp score (TGSS) using a Spearman test, and the progression of TGSS, erosion and joint space narrowing (JSN) scores in groups with low and high disease activity were compared for placebo and TCZ (Kruskal-Wallis). RESULTS:Baseline variables were similar among the groups. Change of TGSS was lower in patients receiving TCZ than placebo (TCZ: 0.29 ± 0.96; placebo: 0.90 ± 1.92; p=0.0007). In patients receiving placebo, the correlation with TGSS change was significant for baseline scores of the simplified disease activity index (SDAI; r=0.18, p=0.047) and swollen joint count 28 (r=0.22, p=0.019), with similar trends for C-reactive protein. Similar correlations were seen for SDAI, clinical disease activity index, disease activity score 28 at 1 year with x-ray change during that year (r=0.26-0.28, p=0.002-0.006). In contrast, none of the baseline or 1-year variables showed significant correlation with x-ray changes in patients receiving TCZ+MTX, suggesting a disassociation of the link between disease activity and damage by TCZ. Finally, for patients in remission or with low disease activity, progression of TGSS, erosion and JSN was similar among treatment groups (TGSS: placebo, 0.4±1.1; TCZ, 0.2 ± 0.7; p=NS), while for patients with moderate or high disease activity placebo-treated patients progression was significantly greater (TGSS: 1.2 ± 2.2 vs 0.4 ± 1.2; p=0.0009). CONCLUSIONS:IL-6 inhibition with TCZ plus MTX retards joint damage progression independently of its impact on disease activity. Similar effects have hitherto been reported only for TNF-i. This indicates that the effects of IL-6 inhibition on progression of joint damage in RA are among the most profound currently attainable.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Smolen JS,Avila JC,Aletaha Ddoi
10.1136/annrheumdis-2011-200395subject
Has Abstractpub_date
2012-05-01 00:00:00pages
687-93issue
5eissn
0003-4967issn
1468-2060pii
annrheumdis-2011-200395journal_volume
71pub_type
杂志文章,随机对照试验abstract::Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocortic...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,杂志文章,评审
doi:10.1136/ard.2009.126532
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:To clarify the deleterious effects of Mayer's haematoxylin staining procedure which result in a decrease in, or complete loss of, the number of calcium pyrophosphate dihydrate (CPPD) crystals, and to determine the proper staining period for preserving the crystals in a histological paraffin section of articul...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.1.80
更新日期:2001-01-01 00:00:00
abstract::Eighty-one patients with 116 osteoarthritic knees were seen by the author at the University College Hospital (UCH), Ibadan in six years. Below the age of 50 the disease was significantly commoner among Nigerians than Caucasians; 39.5% of our patients were less than 50 years old, compared with 1.1% of Caucasians. In co...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.10.682
更新日期:1985-10-01 00:00:00
abstract:OBJECTIVES:To report the results of a pilot study using rituximab combined with Peg-interferon (IFN) alpha2b-ribavirin in severe refractory hepatitis C virus (HCV) related mixed cryoglobulinaemia (MC) vasculitis. METHODS:Sixteen consecutive patients with severe HCV-MC vasculitis that were resistant (n = 11) or relapse...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.2007.081653
更新日期:2008-10-01 00:00:00
abstract:OBJECTIVE:To investigate the involvement of interleukin-1 (IL-1) in the induction or maintenance of the insulin-like growth factor 1 (IGF-1) non-responsive state of chondrocytes during experimental arthritis in mouse knee joints. METHODS:To characterise IGF-1 nonresponsiveness during arthritis, we measured chondrocyte...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.12.976
更新日期:1995-12-01 00:00:00
abstract::Using clinical, radiological, and morbid anatomical data about patients with arthritis of the hip and their femoral heads resected during total hip replacement, an attempt has been made first, to classify patients and femoral heads by a cluster analysis technique, and secondly and more realistically, to use existing c...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.34.4.298
更新日期:1975-08-01 00:00:00
abstract:INTRODUCTION:A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Cauc...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析,多中心研究
doi:10.1136/annrheumdis-2012-201888
更新日期:2013-04-01 00:00:00
abstract::Sepsis is a severe complication of abdominal infections such as peritonitis and is associated with high mortality. Unfortunately, the molecular mechanisms controlling the development of sepsis are still incompletely understood. Interestingly, the interleukin (IL) 12 family member IL27 seems to play a key role in sepsi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2007.078337
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Previous data have shown that etanercept levels are associated with clinical response in rheumatoid arthritis. However, for ankylosing spondylitis (AS), data regarding this topic are inconclusive. OBJECTIVES:To investigate the relationship between etanercept levels and clinical response in patients with AS....
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-205213
更新日期:2015-10-01 00:00:00
abstract::This article gives a short overview of the development and characteristics of the OMERACT rheumatoid arthritis MRI scoring system (RAMRIS), followed by an introduction to the use of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. With this atlas, MRIs of wrist and metacarpophalangeal joints of patien...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2004.031773
更新日期:2005-02-01 00:00:00
abstract:OBJECTIVE:To study the association between the occurrence of peripheral arthritis and of acute anterior uveitis during the course of ankylosing spondylitis (AS). METHODS:Retrospective clinical follow up by both chart review and direct patient interview was performed on 271 individuals comprised of 222 local white and ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.2.128
更新日期:1995-02-01 00:00:00
abstract:OBJECTIVE:To elucidate the clinical importance of the anti-signal recognition particle (SRP) autoantibody in patients with myositis. METHODS:Retrospective systematic assessment of the clinical, laboratory and histological characteristics of 23 anti-SRP-positive patients from six European centres. Data were compared wi...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2006.052191
更新日期:2006-12-01 00:00:00
abstract::In a multicentre study patients with rheumatoid arthritis judged by prevailing criteria to be suitable for synovectomy of the knee or metacarpophalangeal (MCP) joints were randomly allocated to one of two groups. One group had the operation, the other was observed without operation from a notional corresponding date. ...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1975-10-01 00:00:00
abstract:BACKGROUND:Medical management of adults with osteoarthritis (OA) who require non-steroidal anti-inflammatory drugs (NSAIDs) must be decided after assessing prevalent gastrointestinal (GI) and cardiovascular (CV) risks in the individual patient. OBJECTIVE:To evaluate the GI and CV risk profile of patients with OA who r...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2009.123166
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. METHODS:Synovial biopsies were obtained from pat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206921
更新日期:2016-04-01 00:00:00
abstract::After in vitro incubation with 3H-thymidine, the proliferation of synovial lining cells and fibroblasts was investigated in surgically-removed articular tissue. Under normal conditions, in nonrheumatoid arthritis and in osteoarthrosis, low proliferation rates for both cell types were observed. In rheumatoid arthritis,...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.34.3.219
更新日期:1975-06-01 00:00:00
abstract::The relation of habitual knuckle cracking to osteoarthrosis with functional impairment of the hand has long been considered an old wives' tale without experimental support. The mechanical sequelae of knuckle cracking have been shown to produce the rapid release of energy in the form of sudden vibratory energy, much li...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.49.5.308
更新日期:1990-05-01 00:00:00
abstract:OBJECTIVE:To evaluate radiographic features of osteoarthritis (OA) to determine which is more closely associated with knee pain and hence might be used as a radiographic definition of OA in the community. To evaluate joint space width in normal subjects. METHODS:452 subjects from a case-control community study of knee...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.57.10.595
更新日期:1998-10-01 00:00:00
abstract::A study of 163 patients with ankylosing spondylitis seen on 433 occasions showed that active inflammatory disease was strongly associated with the presence of Klebsiella pneumoniae in the faeces (P less than 0.001). Sequential studies showed that in patients with inactive disease the presence of a positive culture for...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.37.2.146
更新日期:1978-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Serum leptin measures are associated with radiographic knee osteoarthritis, but no studies have examined leptin levels with respect to different measures of knee joint damage from MRI. METHODS:Participants in the Michigan Study of Women's Health Across the Nation underwent bilateral knee MRIs ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-202685
更新日期:2014-05-01 00:00:00
abstract:OBJECTIVE:To better understand the characteristics of synoviocytes located in the rheumatoid arthritis (RA) pannus. METHODS:One cell line, termed PSC, was cloned from RA pannus lesions. Phenotypic analysis was done by contrast microscopy, indirect immunostaining, and safranin O staining. Transcription of several proto...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.56.4.262
更新日期:1997-04-01 00:00:00
abstract::We report two cases of osteomyelitis secondary to staphylococcal septicaemia, presenting with large sterile effusions in adjacent joints. In both cases the clinical features were suggestive of septic arthritis. Multiple joints were involved in each patient. Initial radiographs showed no abnormalities. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.43.4.607
更新日期:1984-08-01 00:00:00
abstract:OBJECTIVES:The Psoriatic Arthritis Impact of Disease (PsAID) Questionnaire is a recently developed patient-reported outcome measure (PROM) of disease impact in psoriatic arthritis (PsA). We set out to assess the validity in an independent cohort of patients, estimate the minimally important difference for improvement a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2017-211996
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND:Intra-articular injection of hyaluronan (HA) has been suggested to have a disease-modifying effect in osteoarthritis, but little is known about the possible mechanisms. OBJECTIVE:To investigate the effects of HA species of different molecular mass, including 800 kDa (HA800) and 2700 kDa (HA2700), on the exp...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.086884
更新日期:2009-06-01 00:00:00
abstract::Cellular immunity to cartilage proteoglycans may be responsible for sustaining chronic inflammation in ankylosing spondylitis. This hypothesis was examined by measuring peripheral blood and synovial fluid mononuclear cell proliferation in five preparations of human cartilage proteoglycan monomer in vitro. Peripheral b...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.8.959
更新日期:1992-08-01 00:00:00
abstract:OBJECTIVE:To evaluate the impact of tumour necrosis factor alpha (TNFalpha) blockers on the presence of liver fibrosis in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with methotrexate (MTX). METHODS:Participants were consecutive patients with RA and PsA who had undergone MTX treatment...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.116194
更新日期:2010-06-01 00:00:00
abstract::Adult human articular cartilage has been maintained in organ culture for 8 days, and the culture medium, which was changed on alternate days, was pooled. Normal and rheumatoid cartilage was obtained from patients and 4 types of culture were prepared: (1) cartilage alone; (2) cartilage + D-penicillamine; (3) cartilage ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.39.1.53
更新日期:1980-02-01 00:00:00
abstract:OBJECTIVE:Pregnant women with systemic sclerosis (SSc; scleroderma) have an increased risk of premature delivery and small full-term infants. During placental development, angiogenesis and vascular remodelling are essential for a successful pregnancy outcome. An analysis was made of the pathological changes and express...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.107623
更新日期:2010-02-01 00:00:00
abstract:OBJECTIVE:To review the cost effectiveness of rheumatoid arthritis (RA) treatments and inform the clinical recommendations by the European League Against Rheumatism. METHODS:A systematic literature search and review of the health economic evidence on RA treatment options was performed. RESULTS:Despite diverse methodo...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.2009.126714
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:To study prescription patterns of biological treatment in rheumatoid arthritis (RA) patients in southern Sweden, a region with no formal or economic restrictions for the use of biological treatment in rheumatological diseases. Specifically, we studied conformity with the national Swedish guidelines for biolog...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.070714
更新日期:2008-01-01 00:00:00