Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17079854 [Clinical features of fracture with glucocorticoid induced osteoporosis and rheumatoid art 2006 Nov Fracture in patients with glucocorticoid-induced osteoporosis (GIO) is occurred despite properly maintained bone mineral density. So the criteria of primary osteoporosis cannot be adapted to GIO. This is caused by the difference of disease's pathology. In glucocorticoid therapy, duration and total volume of dosage of the drug affects bone strength, and then the risk of fracture will be increasing. However, even if low dosage of glucocorticoid is used for the patients, the risk of fracture has increased more than that of normal people. The site of fracture is well recognized in vertebral body, hip joint, rib, and sacrum. While, the fracture in patients with rheumatoid arthritis (RA), one of the disease representing GIO, is observed in all of the body, including long bone and periarticular bone in addition to the site of fracture observed in GIO. The risk of fracture in patients with RA is increased by the glucocorticoid daily use and the functional disability.
16184344 [T-lymphocytes--do they control rheumatic immune responses?]. 2005 Sep T cells, in particular CD4(+) T cells, have been implicated in mediating many aspects of rheumatoid inflammation. In rheumatoid arthritis (RA), CD4(+) T cells display various functional abnormalities in the synovium as well as in the peripheral circulation. Current evidence suggests, however, that the role of CD4(+) T cells in the development of rheumatoid inflammation exceeds that of activated pro-inflammatory effector T cells that drive the chronic autoimmune response. Subsets of CD4(+) T cells with regulatory capacity, such as CD25(+) Tregs, have been identified in mice and man, and recent observations suggest that in RA, the function of these regulatory T cells is severely impaired. Thus, in RA, defective regulatory immune mechanisms might allow the breakdown of peripheral tolerance, following which the detrimental CD4(+) T-cell-driven immune response evolves and proceeds to chronic inflammation. Here, we review the functional abnormalities and the contribution of different T-cell subsets to rheumatoid inflammation.
15934837 CDP-870 (certolizumab) in rheumatoid arthritis. 2005 Apr The development of biological anti-TNF-alpha therapy has revolutionised the treatment of rheumatoid arthritis and other inflammatory diseases, and has identified a worldwide market for expensive yet effective therapies for chronic diseases. Certolizumab (CDP-870) is a new agent that employs a novel strategy to neutralise TNF-alpha--namely the prokaryotic expression of TNF-alpha-specific Fab antibody fragments, coupled to polyethylene glycol--to produce a drug that is potentially less expensive to manufacture than other anti-TNF-alpha agents and which may be administered by subcutaneous injection once a month. The background to the ongoing development of this new agent and its clinical effects are discussed in this article.
16027301 No evidence for increased risk of cutaneous squamous cell carcinoma in patients with rheum 2005 Jul OBJECTIVE: To determine the incidence of cutaneous squamous cell carcinoma (SCC) in patients with rheumatoid arthritis receiving etanercept, a tumor necrosis factor antagonist, for up to 5 years. DESIGN: An etanercept clinical trials' database and an etanercept postmarketing surveillance database were retrospectively analyzed for the incidence of SCC. SETTING: Patients enrolled in clinical trials of etanercept were from private and institutional practices. The postmarketing database comprised reports from postmarketing trials and solicited and spontaneous reports. Patients A total of 1442 patients with rheumatoid arthritis with 4257 patient-years of etanercept exposure (median exposure, 3.7 years) are included in the clinical trials' database. More than 125,000 patients with more than 250,000 patient-years of etanercept exposure are included in the etanercept postmarketing database. Interventions Most patients enrolled in clinical trials of etanercept received a dosage of 25 mg of etanercept subcutaneously twice weekly for most of the time they received etanercept therapy. RESULTS: Only 4 cases of SCC were observed in the etanercept clinical trials' database, an incidence that compares favorably with the expected incidences based on general population data from Arizona (13.1) and Minnesota (5.9). Similarly, few cases of SCC (1 per 10,000 patient-years) have been reported during postmarketing surveillance of etanercept therapy. CONCLUSION: In patients with rheumatoid arthritis, etanercept use of up to 5 years does not seem to be associated with an increase in the incidence of cutaneous SCC.
15800008 Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do! 2005 Jul Maintenance of oxygen homoeostasis is the basic principle in cell proliferation, differentiation, survival, and function in all higher organisms. The transcription factor, HIF (hypoxia inducible factor) has a central role in oxygen homoeostasis, and is indispensably linked to energy metabolism. Abnormally reduced oxygen concentrations leading to dysfunctional cell metabolism are found in rheumatoid arthritis and hence, knowledge of the molecular adaptive responses to hypoxia and the involvement of HIF in the pathogenesis of RA are interesting.
16372904 Mediterranean diet or extended fasting's influence on changing the intestinal microflora, 2005 Dec 22 BACKGROUND: Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases. While microbiological fecal culture analysis is now increasingly used, little is known about the relationship of changes in intestinal flora, dietary patterns and clinical outcome in specific diseases. To clarify the role of microbiological culture analysis we aimed to evaluate whether in patients with rheumatoid arthritis (RA) or fibromyalgia (FM) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome. METHODS: During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA (n = 16) or FM (n = 35) were included in the study. According to predefined clinical criteria and the subjects' choice the patients received a mostly vegetarian Mediterranean diet (n = 21; mean age 50.9 +/-13.3 y) or participated in an intermittent modified 8-day fasting therapy (n = 30; mean age 53.7 +/- 9.4 y). Quantitative aerob and anaerob bacterial flora, stool pH and concentrations of secretory immunoglobulin A (sIgA) were analysed from stool samples at the beginning, at the end of the 2-week hospital stay and at a 3-months follow-up. Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients. RESULTS: We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups, nor were significant differences found in the analysis of sIgA and stool ph. Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA (p = 0.09). Clinical outcome was not related to alterations in the intestinal flora. CONCLUSION: Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM. The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques. The potential benefit of fasting treatment in RA and FM should be further tested in randomised trials.
16567357 Improved health-related quality of life for rheumatoid arthritis patients treated with aba 2006 Oct OBJECTIVE: Rheumatoid arthritis (RA) patients who have inadequate response to anti-tumour necrosis factor (TNF) therapy currently have treatment options that are limited and less than optimal in their risk-to-benefit ratio. Abatacept provides a new generation of RA medications that has previously been demonstrated to have positive clinical outcomes with this population. The current study sought to demonstrate the efficacy of abatacept on quality of life (QoL) for RA patients with inadequate response to anti-TNF therapy. METHODS: Patients were entered into a double-blind, placebo-controlled, multicentre randomized clinical trial, with 258 patients randomized to abatacept + disease-modifying anti-rheumatic drugs (DMARDs) and 133 patients randomized to placebo + DMARDS. The QoL was measured with the Short Form Health Survey (SF-36), Health Assessment Questionnaire (HAQ) and fatigue visual analogue scale, and was analysed with basic (ANOVA, chi-square) and multigroup growth curve techniques to assess differential change over time. RESULTS: Treatment group QoL improved significantly more than placebo on the HAQ and fatigue indices, as well as seven of the eight SF-36 scales and SF-36 physical and mental summary scores. Improvement rate was faster for abatacept than for placebo on the QoL measures, and the improvements from abatacept related to normal levels of QoL on many domains. CONCLUSION: Clinically relevant benefits of abatacept over placebo are discussed regarding improving QoL. Importantly, the larger rate of change for abatacept over placebo provides clinicians with a medication that can lead to meaningful changes in a patient's life within a few weeks, even when the patient previously failed anti-TNF therapy.
15840096 Prevention of amputation caused by rheumatic diseases following a novel therapy of exposin 2005 Apr BACKGROUND: Wounds with exposed bones caused by rheumatic diseases commonly result in amputation despite progress in our understanding of wound-healing mechanisms. OBJECTIVES: To determine whether an experimental therapy of bone marrow exposure, an occlusive dressing and subsequent grafting of epidermal sheets accelerates healing and reduces the need for amputation in patients with rheumatic diseases. METHODS: Fifteen patients, including those with rheumatoid arthritis or systemic sclerosis, who had wounds with exposed bones were treated either with the standard procedure, consisting of local wound care, debridement with a scalpel, bed rest and parenteral antibiotics (n = 8), or with a newly developed experimental procedure (n = 7). In that new procedure, the affected bone was initially exposed by debridement with a scalpel, followed by partial excision with a bone scraper until bleeding was observed from the exposed bone. The lesions were immediately covered with an occlusive dressing, and were eventually treated with epidermal grafts obtained from suction blisters. RESULTS: A comparison with standard therapy demonstrated that the time needed for wound healing was similar, but that the newly developed combination therapy reduced the risk of amputation (P = 0.020). No skin ulcers or erosions were observed for at least 1 year in five of seven patients (72%) due to the adoption of stable palmoplantar-type characteristics in grafts derived from the trunk epidermis. CONCLUSIONS: Our study indicates that exposure of bone marrow cells plus an occlusive dressing accelerates the healing of skin ulcers at least partly through the preparation of a healthy well-granulated wound bed and that subsequent epidermal grafting achieves site-specific differentiation through epithelial-mesenchymal interactions.
15681247 Correlations between high-resolution computed tomography of the chest and clinical functio 2005 Jan INTRODUCTION: The contribution of computed tomography (CT) to the assessment of rheumatoid lung disease is universally recognized. Our objective was to define the usefulness of high-resolution CT (HRCT) in evaluating lung abnormalities in unselected patients with rheumatoid arthritis (RA) and to determine whether HRCT findings were correlated with clinical and lung function test (LFT) abnormalities. PATIENTS AND METHODS: We prospectively investigated HRCT findings in 75 consecutive RA patients and looked for correlations with clinical, radiological, blood gas, and LFT variables. The 63 women and 12 men had a mean age of 48+/-14 years and a mean disease duration of 8+/-88 months (2 months-27 years). Most of the patients (77.3%) had no known history of respiratory disease. RESULTS: Respiratory symptoms were noted in one third of patients. HRCT findings were abnormal in 49.3% of patients, showing interstitial disease in 28% and bronchiectasis in 18.7%. Advanced fibrosis was not noted. One patient had bronchiolitis obliterans with organizing pneumonia and another had constrictive bronchiolitis. Smaller proportions of patients had emphysema (13.3%), alveolar involvement (12%), pleural involvement (9.3%), or rheumatoid nodules (4%). HRCT findings were abnormal in 48.6% of the patients with no respiratory symptoms. Factors significantly associated with HRCT abnormalities were age older than 40 years, positive tests for IgM rheumatoid factors, hypoxia at rest, and LFT evidence of distal airway disease. Neither Sjogren's syndrome nor RA duration was significantly associated with the risk of HRCT abnormalities. CONCLUSION: In our population of unselected RA patients, HRCT proved sensitive in detecting abnormalities that were clinically silent and missed by plain radiography. Correlations between HRCT abnormalities and results of other investigations were inconsistent. Thus, these various investigations may complement one another.
17183621 The economic burden of rheumatoid arthritis in a developing nation: results from a one-yea 2007 Jan OBJECTIVE: To assess annual direct and indirect costs in a prospective cohort of patients with rheumatoid arthritis (RA) in Thailand from the societal perspective. METHODS: Data on costs and intangible losses were prospectively collected at regular intervals over a one-year period from 158 RA patients who attended a major tertiary care facility in Bangkok, Thailand. Direct medical, direct nonmedical, indirect, and total costs were estimated according to patients' respective health insurance conditions and converted to 2001 US dollars using published purchasing power parity estimates. Sensitivity analyses were performed and the predictors of costs and intangible losses were investigated. RESULTS: The average societal cost of RA was estimated to be 2682 US dollars, 41.4% of patients' average annual income. Average direct and indirect costs were estimated to amount to 2135 US dollars and 547 US dollars per patient per year, respectively. Seventy-three patients (46.2%) experienced at least one event of intangible losses and 46 patients (29.1%) had decreased earnings ability because of RA. Poor physical function, joint deformity, high number of disease modifying antirheumatic drugs, and steroid use contributed to higher costs and presence of intangible losses. CONCLUSION: RA consumes a significant proportion of patients' annual average incomes and poses a significant economic burden to society. Since RA mainly affects a working-age population, early and timely treatment of this disease can improve both the suffering and the economic productivity of patients in Thailand.
17064872 Benign, atypical and malignant lymphoproliferative disorders in rheumatoid arthritis patie 2006 Dec Lymphadenopathy, which may be associated with systemic symptoms, is frequently associated with rheumatoid arthritis (RA). Reactive non-neoplastic tissue comprises the majority of the lymph node lesions. However, several cohort studies have demonstrated that RA has an increased risk of non-Hodgkin's lymphomas (NHLs). Since the early 1990s, an atypical or malignant lymphoproliferative disorders (LPD) in patients immunosupressed with methtorexate (MTX) therapy for RA has been emphasized, namely MTX-associated LPDs. Epstein-Barr virus (EBV) has received attention in connection with the etiology of RA. The present review describes the clinicopathologic and immunohistochemical findings of reactive, atypical and malignant LPDs associated with RA along with the presence or absence of EBV in LPDs using the in situ hybridization (ISH) method. The majority of reactive lymph node lesions exhibit reactive follicular hyperplasia with interfollicular polyclonal plasmacytosis. Atypical LPDs rarely appears in RA patients. However, these cases occasionally pose difficult problems in the differential diagnosis from malignant lymphomas associated with RA or atypical and malignant LPDs showing RA-like clinicopathological findings. Clinicopathologically, three types of atypical LPDs have delineated, i.e. (i) resembling multicentric Castleman's disease (MCD); (ii) atypical paracortical hyperplasia with lymphoid follicles (APHLF) and; (iii) atypical lymphoplasmacytic immunoblastic proliferation. Malignant lymphoma associated with RA is characterized by; (i) predominance of elderly cases; (ii) usually female predominance, reflecting the sex ratio of RA; (iii) longstanding history of RA; (iv) relatively frequent advanced stage of disease; (v) majority of the patients had the B-cell phenotype; and (vi) an increased frequency of diffuse large B-cell lymphoma (DLBCL) in RA. It is unlikely that EBV is the causative agent of either reactive or atypical LPD. Among malignant lymphomas, EBV-associated lymphoma comprised only a small fraction of all NHLs in the general RA patient population.
15931231 Evidence of a pharmacogenomic response to interleukin-l receptor antagonist in rheumatoid 2005 Sep Biological activity of the IL-1 system depends on the balance between two proinflammatory proteins (IL-1alpha and IL-1beta) and the related anti-inflammatory protein, the IL-1 receptor antagonist (IL-1Ra). The genes for these proteins lie within 430 kb on human chromosome 2. Based on a clinical trial of human recombinant IL-1ra in rheumatoid arthritis, we tested whether IL-1 genotype might be related to the likelihood of response to anti-IL-1 therapy. A positive response was defined as a reduction of at least 50% in the number of swollen joints by week 24, following treatment with either 150 mg/day IL-1ra or placebo. The response rate to treatment, independent of genotype, was 48% (44/91). A highly significant association was found between carriage of the rarer allele at IL1A(+4845) and response to treatment (P=0.0009; OR=4.85 (1.85,12.70)). The response rate in patients carrying this allele was 63.4% compared with 26.3% in noncarriers. A weaker association was found for IL1B(+3954) (P=0.02). There was a highly significant interaction between treatment (150 mg/day or placebo) and the composite genotype across IL1A(+4845) and IL1B(+3954) (P=7.6 x 10(-5)). No associations with IL-1 genotypes were found in patients receiving placebo. Thus, a significant pharmacogenomic effect was found in the treatment of RA patients with recombinant IL-1ra.
16970089 [Study on the differential gene expression of peripheral CD4+ among rheumatoid arthritis p 2006 Aug OBJECTIVE: To explore the differential gene expression of peripheral CD4+ among rheumatoid arthritis (RA) patients of cold or heat syndrome type with or without rheumatoid factor (RF). METHODS: Differential gene expression of peripheral CD4+ lymphocytes purified from fasting venous blood of RA patients and healthy subjects was studied using gene chip technique. RESULTS: There were 55 differential genes between RA patients with and without RF, mainly involving those related with immune response and signal transduction. In patients with RF, 71 differential genes, mainly related with functional metabolism and immune response, and in those without RF, 70 related with functional metabolism were found between patients of cold and heat syndrome type respectively, all of them were not repetitive with the above-mentioned 55, and only 2 were found repetitive between the 70 and the 71 differential genes, mainly involving functional metabolism. CONCLUSION: The differential genes between RA patients with or without RF are different with those between patients of heat and cold syndrome type, suggesting the TCM syndrome classification has its own basis of gene expression profile.
16716286 Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab th 2006 Oct OBJECTIVE: To examine protein oxidation in rheumatoid arthritis (RA) and evaluate its evolution after infliximab therapy in a subgroup of patients. METHODS: Seventy-one consecutive patients with RA were included. Among them, 30 patients refractory to conventional therapy were treated with infliximab. Serum markers of oxidative stress were determined at baseline and before the infusions of infliximab at weeks 6 and 30. Baseline values were compared with those in 30 healthy volunteers. RESULTS: Mean levels of serum carbonyl groups were significantly higher in RA patients than in controls (1.29+/-0.76 versus 0.58+/-0.39 nmol/mg of protein, p<0.0001), whereas thiol levels were found to be lower (238.3+/-61.6 versus 316.5+/-54.8 micromol/L, p<0.0001). Thiol levels inversely correlated with the disease activity score (r=-0.42, p=0.004), and with CRP values (r=-0.45, p=0.001). Immunoblots showed that albumin and heavy chain immunoglobulin were oxidized more markedly than in healthy volunteers. Significantly lower levels of thiol groups were detected in patients with refractory RA disease (208.9+/-66.8 versus 264.2+/-43.0 micromol/L, p<0.0004) but concentrations of carbonyl groups were similar. Short-term treatment with infliximab significantly decreased carbonyl groups (0.97+/-0.47 nmol/mg protein, p=0.02) and increased thiol (231.2+/-48.7 micromol/L, p=0.02) levels. CONCLUSION: Our results highlight free radical protein damage in RA and a link with inflammation, as underlined by the beneficial effects of infliximab.
15850996 Asymmetry of small joint involvement in rheumatoid arthritis: prevalence and tendency towa 2005 May OBJECTIVES: To quantify asymmetry of radiological joint damage in rheumatoid arthritis (RA), to determine whether asymmetrical damage to joints in RA becomes symmetrical over time, and to identify factors predictive of symmetrization. METHODS: In phase 1, initial, mid-term (mean follow-up: 3 years) and late (mean follow-up: 8 years) radiographs of 48 patients with definite RA (English population) were graded by the Modified Larsen (ML) system. In phase 2, 27 subjects (Canadian population) with at least one asymmetrical pair of joints in the hands or feet were identified. Two successive radiographs of 77 asymmetrical joints, separated by at least 2 years, were compared. Clinical and biological factors were assessed for their ability to predict symmetrization, defined as a reduction in side-to-side difference over time of two or more ML grades. RESULTS: In phase 1, the overall rate of asymmetry was 12.9% (95% CI: 11.2-14.5%), increasing from 9.7% (first visit) to 13.8% (mid-term) and 14.4% (last visit). Metacarpophalangeal (MCP) joints were more frequently asymmetrical than thumb (MCP and interphalangeal) joints (P = 0.0064) and proximal interphalangeal (PIP) joints (P < 0.0001); wrist quadrants were more frequently asymmetrical than PIP joints (P < 0.0001). In phase 2, two groups were identified and compared: symmetrizers (22 joints) and non-symmetrizers (55 joints). The overall probability of small joints in the hand and foot symmetrizing was 28.5%. Rheumatoid factor (RF) was predictive of symmetrization. The risk of symmetrization was significantly increased in RF-positive patients with asymmetric joints (P = 0.01). The prevalence of asymmetry did not decrease with disease duration, despite symmetrization. CONCLUSIONS: Prevalence of asymmetry in joint damage in RA was 13-16%. Symmetry was more evident in PIP joints than in MCP and wrist joints. Seropositive patients are more than twice as likely to symmetrize than seronegative patients. Data regarding the tendency for symmetrization may have value in the clinical management of RA patients with asymmetrical joint damage.
15365781 The sesamoid index in psoriatic arthropathy. 2005 Apr OBJECTIVE: The sesamoid index was originally described as an aid to the diagnosis of acromegaly. We performed this study to assess the value of the thumb sesamoid index in the diagnosis of psoriatic arthropathy. DESIGN: Retrospective measurement of the sesamoid index (length x width of the medial thumb sesamoid), along with the age and sex were recorded for patients as described below. Patients with psoriasis were subdivided into those with or without radiographic evidence of hand arthropathy. PATIENTS: Fifty-nine consecutive patients attending rheumatology clinics with arthralgia and psoriasis were studied. Comparison groups with radiographic evidence of rheumatoid arthritis (52 patients), osteoarthritis (44) or normal hands (55) were also recorded. RESULTS: Twenty-one of 59 patients with psoriasis and arthropathy had a sesamoid index>40, compared with two of 52 with rheumatoid arthritis, none of 44 with osteoarthritis and none of 55 normals. CONCLUSIONS: Psoriatic arthropathy is a recognised cause of bone enlargement, usually in the phalanges due to periostitis and proliferative enthesopathy. We have confirmed that psoriatic hand arthropathy can cause significant enlargement of the thumb sesamoids, a feature which is easily quantified and may assist diagnosis.
16763464 Osteoclasts, rheumatoid arthritis, and osteoimmunology. 2006 Jul PURPOSE OF REVIEW: Osteoclasts are terminally differentiated cells of the monocyte/macrophage lineage that resorb bone matrix. Bone destruction in rheumatoid arthritis is mainly attributable to the abnormal activation of osteoclasts, and studies on activation of osteoclasts by the immune system have led to the new research field called osteoimmunology. This interdisciplinary field is very important to biologic research and to the treatment of diseases associated with the bone and immune systems. RECENT FINDINGS: The T-cell-mediated regulation of osteoclast differentiation is dependent on cytokines and membrane-bound factors expressed by T cells. The cross-talk between receptor activator of nuclear factor-kappaB ligand and interferon-gamma has been shown to be crucial for the regulation of osteoclast formation in arthritic joints. Recent studies indicate that an increasing number of immunomodulatory factors are associated with the regulation of bone metabolism: nuclear factor of activated T cells c1 has been shown to be the key transcription factor for osteoclastogenesis, the activation of which requires calcium signaling induced by the immunoglobulin-like receptors. SUMMARY: New findings in osteoimmunology will be instrumental in the development of strategies for research into the treatment of various diseases afflicting the skeletal and immune systems.
16465613 Rheumatoid arthritis: links with cardiovascular disease and the receptor for advanced glyc 2006 Jan Cardiovascular (CV) disease is increased in patients with chronic inflammatory disease, including rheumatoid arthritis (RA). Furthermore it has become clear at a pathophysiological level, that atherosclerosis has striking similarities with autoimmune disease. This realization has come at a time of paradigm shift in how rheumatologists manage RA, with the availability of biological agents targeting key inflammatory cytokines. This review will focus on the possible causes of increased vascular disease in RA, including the role of traditional CV risk factors. Mechanisms potentially at play, such as C-reactive protein (CRP), altered coagulation, and cyclooxygenase (COX)-2 inhibitors will be covered in brief. The receptor for advanced glycation end products (RAGE) has been identified as a candidate molecule influencing response to ongoing inflammation and autoimmunity. There will be a focus on the role of RAGE in CV disease and RA. As has been the case with many novel molecules, functional polymorphisms are thought to alter disease expression and assist us in coming to terms with the biological activities of the parent molecule. The review will conclude with a discussion of the potential role of the RAGE Glycine 82 Serine polymorphism.
16249825 The alpha 2 type IX collagen gene tryptophan polymorphism is not associated with rheumatoi 2006 Jul The aim of this study was to investigate whether the alpha 2 type IX collagen (COL9A2) polymorphism that introduces tryptophan residue into the collagen triple-helix is a marker of susceptibility to, or severity of, rheumatoid arthritis (RA). The study included 749 Japanese patients with RA. One hundred twenty-four unrelated healthy individuals served as the control subjects. The relationship between the COL9A2 gene polymorphism and clinical manifestations of RA was evaluated. For the number of subjects positive for COL9A2 tryptophan polymorphism, there was no statistically significant difference between RA patients and normal controls. Furthermore, we did not detect any association of COL9A2 tryptophan polymorphism with disease status, least erosive subset, more erosive subset, or mutilating disease. The lack of association of COL9A2 tryptophan polymorphism with RA and the clinical findings in our study implies that the polymorphism may not function as a candidate gene marker for screening RA patients.
16504992 Are American College of Rheumatology 50% response criteria superior to 20% criteria in dis 2006 Dec OBJECTIVE: To carry out a meta-analysis designed to compare the discriminant capacities of American College of Rheumatology 50% (ACR50) with 20% (ACR20) responses in clinical trials on rheumatoid arthritis reported after 1997 and to analyse whether ACR50 can be as informative as ACR20 in distinguishing active from control treatments in more recent trials. METHODS: Clinical trials on rheumatoid arthritis reported since 1997 were identified, which included aggressive combinations of disease-modifying antirheumatic drugs and glucocorticoids, as well as powerful new agents-leflunomide, etanercept, infliximab, anakinra, adalimumab, abatacept, tacrolimus and rituximab. A meta-analysis of ACR20 compared with ACR50 responses for 21 clinical trials was carried out on differences in proportions of responders for active and control treatments and corresponding odds ratios (ORs). RESULTS: In all but one clinical trial on rheumatoid arthritis published since 1997 with data available on ACR20 and ACR50, more than 50% of patients who were ACR20 responders among those randomised to active treatment were also ACR50 responders. This phenomenon was seen for control groups in 38% of trials, many of which included treatment with methotrexate. A meta-analysis of the clinical trials indicated a slight advantage to ACR50 for quantifying treatment comparisons, not significant for differences in proportions but significant for ORs. CONCLUSION: ACR20 and ACR50 seem to be similar in distinguishing active from control treatments in clinical trials on rheumatoid arthritis reported since 1997. As ACR50 represents a considerably stronger clinical response, ACR50 may be a preferred end point for contemporary clinical trials on rheumatoid arthritis.