Abstract:
:Current drug development programs produce high quality data on the efficacy of new drugs, substantial data on safety, but little data on actual applicability of the new product compared to standard of care. After successful registration and launch, such data require years to accumulate and often remain incomplete. This viewpoint proposes a new trial design for phase 2 and 3 drug trials in rheumatoid arthritis. In this design the trial starts conventionally: patients that are inadequate responders to standard treatment (usually methotrexate) are randomised to receive the experimental drug or placebo on the background of continued (methotrexate) treatment. However, after 3 months all patients in the placebo group are additionally treated with one and the same standard of care treatment (usually an inhibitor of tumour necrosis factor) and all patients in the experimental group are additionally treated with a placebo corresponding to the chosen standard of care treatment. This design allows primary assessment of efficacy and safety of the experimental drug compared with placebo at the ethically acceptable limit of 3 months, followed by secondary assessments of efficacy (including durability) and safety compared to standard of care. The secondary assessments are observational and thus more prone to bias, but it is argued that the potential for bias is limited in this setting. Widespread adoption of the design will greatly help to determine the place of a new product in the spectrum of treatment possibilities of rheumatoid arthritis.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Boers Mdoi
10.1136/ard.2009.110007subject
Has Abstractpub_date
2010-01-01 00:00:00pages
4-6issue
1eissn
0003-4967issn
1468-2060pii
69/01/4journal_volume
69pub_type
评论,杂志文章abstract::One hundred and two rural patients and 100 urban patients with rheumatoid arthritis and osteoarthrosis and 203 age and sex matched controls were visited in their homes to evaluate their problems, needs, and expectations. Although one would expect disability to affect the mobility of a person, it was found that rural p...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.47.2.150
更新日期:1988-02-01 00:00:00
abstract:OBJECTIVES:To determine the probability of drug continuation in a large cohort of methotrexate treated rheumatoid arthritis (RA) patients, the reasons for discontinuation of methotrexate, the overall survival of the members of this cohort, and the causes of death in these patients. METHODS:Yearly follow up was conduct...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.9.708
更新日期:1995-09-01 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::During 1978 a survey was carried out on 34 036 people in Nagano Prefecture, Japan, in an epidemiological study of hyperuricaemia; 15 713 males and 18 324 females were examined by means of our health examination car. The subjects of the survey were all volunteers. The results have shown that the serum uric acid (SUA) l...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.41.3.272
更新日期:1982-06-01 00:00:00
abstract:OBJECTIVES:To review systematically the available literature on the optimal dosage and route of administration of methotrexate in patients with rheumatoid arthritis (RA), as an evidence base for generating clinical practice recommendations. METHODS:A systematic literature search was carried out in MEDLINE, EMBASE, Coc...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1136/ard.2008.092668
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) tends to remit during pregnancy, with more patients achieving remission in the third trimester, coinciding with an increase in levels of alpha-fetoprotein (AFP). In vitro and animal studies have shown that AFP has immunomodulatory properties. MM-093 is a non-glycosylated, recombinan...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/ard.2006.059436
更新日期:2007-05-01 00:00:00
abstract:OBJECTIVE:To examine the hypothesis that aggrecan, cartilage oligomeric matrix protein (COMP), and bone sialoprotein (BSP) concentrations in synovial fluid could provide information on variations of progression of joint destruction in rheumatoid arthritis. METHODS:Aggrecan, COMP, and BSP were quantified by enzyme link...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.56.2.91
更新日期:1997-02-01 00:00:00
abstract::A simple method is described which allows sequential monitoring of the endocytic activity of blood and synovial fluid cells from rheumatoid arthritis patients undergoing therapy with levamisole. Evidence of immediate (24 hours) and long-term (5-7 weeks) cellular phagocytic enhancement is presented. ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.40.4.382
更新日期:1981-08-01 00:00:00
abstract::The effects of dietary fatty acid supplementation on various disease parameters in the spontaneously autoimmune MRL-mp-lpr/lpr mouse model of systemic lupus erythematosus before onset of disease were investigated. A fat deficient diet was supplemented with the following oils: olive oil, sunflower oil, evening primrose...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.45.12.1019
更新日期:1986-12-01 00:00:00
abstract:OBJECTIVE:To compare ultrasound measurement of median nerve cross-sectional area (CSA) at different anatomical landmarks and to assess the value of power Doppler signals within the median nerve for diagnosis of carpal tunnel syndrome (CTS). METHODS:A prospective study of 135 consecutive patients with suspected CTS und...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-202328
更新日期:2013-12-01 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:OBJECTIVE:To study the association between silica exposure, separately as well as combined with smoking, and the risk of developing rheumatoid arthritis (RA) with or without the presence of antibodies against citrullinated peptide antigens (ACPA). METHODS:This Swedish population based case-control study analysed 577 i...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.114694
更新日期:2010-06-01 00:00:00
abstract::Peritoneal serositis is not a widely recognised aspect of systemic lupus erythematosus (SLE). Indeed, ascites in SLE is said to occur only when complicated by the nephrotic syndrome, congestive cardiac failure, or hepatic cirrhosis. We describe two patients who developed ascites that could be attributed to none of the...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.11.778
更新日期:1985-11-01 00:00:00
abstract:AIM:To assess the prevalence and the nature of autonomic neuropathy (AN) in 17 patients with inactive or mild active systemic lupus erythematosus (SLE). METHODS:Patients were tested using questionnaires related to possible AN symptoms, and four non invasive cardiovascular autonomic function tests at rest, during lying...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.53.10.671
更新日期:1994-10-01 00:00:00
abstract::Naproxen at 10 mg per kg body weight was compared with aspirin at 80 mg per kg body weight in children suffering from juvenile chronic polyarthritis. It was found to be as effective as aspirin, with certainly no more and possibly fewer gastrointestinal side effects. A long-term tolerance study up to 12 months confirme...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.38.2.152
更新日期:1979-04-01 00:00:00
abstract:BACKGROUND:Dendritic cells orchestrate pivotal immunological processes mediated by the production of cytokines and chemokines. OBJECTIVE:To assess whether neutralisation of tumour necrosis factor alpha (TNF alpha) during maturation of dendritic cells affects their phenotype and behaviour, which might explain the benef...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2004.023259
更新日期:2005-03-01 00:00:00
abstract:BACKGROUND:The MEFV gene is responsible for familial Mediterranean fever (FMF). Several disease associated mutations have been identified. The range of genetic variation in MEFV in Greek patients has not been determined. OBJECTIVE:To describe a method that facilitates the routine screening of the entire coding sequenc...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.009258
更新日期:2004-04-01 00:00:00
abstract:OBJECTIVE:To describe the associations between overweight measures in childhood and knee pain, stiffness and dysfunction among adults 25 years later. METHODS:Subjects broadly representative of the Australian population (n=449, aged 31-41 years, female 48%) were selected from the Australian Schools Health and Fitness S...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204161
更新日期:2015-04-01 00:00:00
abstract:OBJECTIVES:There is a lipid paradox in rheumatoid arthritis describing that despite low lipids related to systemic inflammation, there is an increased cardiovascular (CV) risk. Our aim was to evaluate if baseline lipid levels or baseline systemic inflammation were associated with the statin dose sufficient to achieve l...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204636
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Entheseal fibrocartilage (EF) derangement is hypothesised to be pivotal to the pathogenesis of spondyloarthritis. Ultrasound is useful for visualisation of the enthesis but its role in EF visualisation is uncertain. This work aimed to demonstrate face and content validity of ultrasound for EF visualisation b...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2009.127175
更新日期:2010-12-01 00:00:00
abstract::A 46 year old man presented with a growing mass over his wrist. Erosions of the triquetrum and hamate were present radiographically. Magnetic resonance imaging (MRI) showed a solid mass arising from the extensor carpi ulnaris tendon, which was T(1) hypointense and isointense, T(2) hypointense, and bloomed on gradient ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.6.550
更新日期:2001-06-01 00:00:00
abstract:OBJECTIVE:To investigate the role of the HS1,2 enhancer polymorphisms as a new candidate marker for rheumatoid arthritis (RA) and to define the possible association with autoantibody positivity and clinical outcome. METHODS:Genomic DNA was obtained from two cohorts of patients with RA (100 with early RA (ERA) and 114 ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.095414
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVE:To analyse fibronectin (FN) gene polymorphisms in type II mixed cryoglobulinemic syndrome (MCsn), an immune-complex mediated systemic vasculitis linked to hepatitis C virus (HCV) infection and characterised by rheumatoid factor (RF) positive B-cell proliferation at high risk for the progression into non-Hodgk...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2006.067637
更新日期:2008-01-01 00:00:00
abstract::Serum IgG antibodies to native and denatured human type II collagen (Col II) were measured using an enzyme linked immunosorbent assay (ELISA). One hundred and thirty one patients with various forms of arthritis such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PSA). Reiter's Syndrome...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.47.4.313
更新日期:1988-04-01 00:00:00
abstract:BACKGROUND:Matrix metalloproteinase (MMP)1, interleukin(IL)6 and vitamin D receptor (VDR) have been implicated in the biological cascade of events initiated by particulate wear debris and bacterial infection, resulting in periprosthetic bone loss around loosened total hip replacements (THRs). The individual responses t...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.062018
更新日期:2007-08-01 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::The question 'Does the use of second-line therapy confer long-term benefit on outcome measures in rheumatoid arthritis?' remains unanswered. The major obstacle which prevents collection of the necessary data is the lack of a suitable control group. In this report experience with three 'second-line placebo groups' is d...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,评审
doi:10.1136/ard.44.2.134
更新日期:1985-02-01 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:BACKGROUND:Small studies have linked α1 antitrypsin (α1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). OBJECTIVE:To test the validity and the mechanism of this association between α1AT and AAV. METHODS:The distribution of α1AT deficiency alleles Z and S was co...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2011.153569
更新日期:2011-10-01 00:00:00
abstract::The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2012-202715
更新日期:2013-03-01 00:00:00