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ID PMID Title PublicationDate abstract
16476768 Human antibodies induce arthritis in mice deficient in the low-affinity inhibitory IgG rec 2006 Feb 20 Rheumatoid arthritis (RA) is a complex autoimmune disease with a poorly understood pathogenesis. The disease is associated with polyclonal B cell activation and the production of autoantibodies (autoAbs), but there is a longstanding controversy as to whether such Abs contribute to, or are secondary to, the pathogenesis of RA. To address the potential pathogenicity of human RA-associated Abs, we developed a passive transfer model involving mice deficient in the low-affinity inhibitory Fc receptor, FcgammaRIIB. We report that plasma or serum from patients with active RA can induce inflammation and histological lesions in FcgammaRIIB-/- mice consistent with arthritis, and that this pathogenic activity is caused by the immunoglobulin G-rich fraction. Our results suggest that humoral autoimmunity can contribute directly to autoimmune arthritis, and that FcgammaRIIB-/- mice are a promising model to evaluate the arthritogenic potential of human autoAbs.
15896801 Improved multiplex immunoassay performance in human plasma and synovial fluid following re 2005 May Cytokines, chemokines and soluble adhesion molecules interact in a complex network within the immune system. Fingerprinting of these proteins may allow the use of these proteins as biomarkers for identification of disease, disease subtyping and monitoring therapeutic interventions. We developed a multiplex immunoassay (MIA) for the detection of 30 proteins in a variety of human body fluids such as plasma and synovial fluid (SF). The measurement of these proteins is hampered by the presence of human (auto-) antibodies, which can cause non-specific binding. We have validated a novel approach for the removal of interfering immunoglobulins using pre-absorption with protein-L. Interfering (auto-) antibodies, such as rheumatoid factor (RF), were removed using three methods; polyethylene glycol (PEG) precipitation, pre-absorption with human gamma-globulin or pre-absorption with protein-L. A significant decrease of RF was observed after a 2 h incubation with protein-L. RF IgM levels were reduced by 89% whereas total IgM, IgG and IgA levels were reduced by 60%. Residual immunoglobulins were blocked with rodent serum and did not interfere with the multiplex immunoassay. Comparing the MIA with a conventional enzyme-linked immunosorbent assay (ELISA) using a panel of spiked plasma samples resulted in correlation coefficients for all mediators between R2 = 0.88 and R2 = 0.99. Intra-assay variance was less than 10% whereas inter-assay variance ranged between 6% and 16%. Pathological samples with heterophilic antibodies hamper immunoassays such as ELISA and MIA. We show that pre-absorption with protein-L is a powerful tool for removal of interfering immunoglobulins from human bodily fluids to be used in immunoassays for studying changes in protein patterns.
16355332 Outcome of prosthetic joint infection in patients with rheumatoid arthritis: the impact of 2006 Jan 15 BACKGROUND: Prosthetic joint infection in patients with rheumatoid arthritis is a serious complication of total joint arthroplasty. Little information is available on the outcome of medical and surgical treatments of prosthetic joint infection in patients with rheumatoid arthritis. METHODS: We conducted a retrospective analysis of all patients with rheumatoid arthritis and a total hip or total knee arthroplasty infection evaluated at Mayo Clinic (Rochester, MN) between 1 January 1969 and 31 December 1995. RESULTS: A total of 200 first episodes of prosthetic joint infection in 160 patients with rheumatoid arthritis were diagnosed during the study period. Thirty-seven percent of prosthetic joint infection episodes were due to Staphylococcus aureus. Of these episodes, 23% and 19% were treated with debridement and retention of components and 2-stage exchange, respectively. The type of surgical procedure was the only analyzed clinical variable that was associated with treatment failure (P < .001). Rates of 5-year survival free of treatment failure for patients with prosthetic joint infection episodes treated with debridement and retention of components, 2-stage exchange, and resection arthroplasty were 32% (95% confidence interval [CI], 21%-49%), 79% (95% CI, 66%-93%), and 61% (95% CI, 49%-74%), respectively. CONCLUSIONS: S. aureus is the most common pathogen among patients with rheumatoid arthritis with prosthetic joint infection. Two-stage exchange was used in only 19% of the prosthetic joint infection episodes among patients with rheumatoid arthritis during the study period, but it was associated with the best outcome. The variable most strongly associated with the outcome was the type of surgical procedure.
17077014 [Study of the humoral immune suppression of recombinant human collagen type II peptide 250 2006 Nov AIM: To investigate the modulation of rhC II 250-270 peptide on special humoral immune response in the course of oral administration. METHODS: ELISA was used to determine antigen-specific antibodies in mice sera. The frequency of anti-C II and anti-C II (250-270) antibody-forming spleen cells was measured by ELISPOT. RESULTS: The level of C II- and C II (250-270)- specific IgG in serum from the mice fed with rhC II (250-270) were (0.82+/-0.02) and (0.84+/-0.04) respectively, and lower significantly than those of collagen-induced arthritis (CIA) control group. The anti-C II (250-270) antibody responses were suppressed obviously (P<0.01). The frequency of antibody-forming cells in the spleen from rhC II (250-270)-fed mice were (158+/-9 counts/well) and (181+/-10 counts/well) respectively, and also were reduced significantly when compared with that in CIA control group (247+/-16 counts/well)(P<0.05). CONCLUSION: Oral rhC II (250-270) could induce specific suppression of humoral responds in CIA. These findings together with a better understanding of the mechanisms of oral tolerance and regulation of humoral immune response in CIA, will help the development of innovative therapeutic intervention for rheumatoid arthritis.
16220290 Kynurenic acid, an endogenous constituent of rheumatoid arthritis synovial fluid, inhibits 2006 Mar Kynurenic acid is an antagonist of ionotropic glutamate receptors. It has been found that glutamate antagonists inhibit proliferation of different human tumor cells. Since the hyperplasia of synovial fibroblasts is one of the most striking features of inflammatory arthritis, the main goals of this study were detection and quantification of kynurenic acid in synovial fluid obtained from patients with rheumatoid arthritis, and determination of its effect on proliferation of synoviocytes in vitro. Presence of kynurenic acid was determined by HPLC in all 58 samples of synovial fluid. The mean concentration was 15.89 pmol/ml. Kynurenic acid inhibited synoviocyte proliferation with the IC50 value of 5.9 mM. In subthreshold concentration of 0.3 mM it enhanced antiproliferative action of celecoxib and nimesulide. In conclusion, the presence of kynurenic acid in synovial fluid was documented in patients with rheumatoid arthritis. Its potential role as an endogenous substance, controlling synoviocyte proliferation can be suggested.
16467034 A two-year follow-up of work capacity in early rheumatoid arthritis: a study of multidisci 2006 Jan OBJECTIVE: To explore changes in sick leave patterns and work ability in patients with early rheumatoid arthritis (RA). The patients received active team support focusing on vocational rehabilitation, in addition to treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: This is an observational study of 110 patients with early RA aged 18-60 years and not permanently disabled. All patients were monitored regularly during a 2-year period by a team comprising a nurse, an occupational therapist, a physiotherapist, a rheumatologist, and a social worker. Intervention included work-site visits and rehabilitation meetings with the employer and the official from the local social insurance office in addition to DMARD treatment and different individual treatments, and support from the team members. RESULTS: The number of patients working full-time increased from 65 to 74 (14%), those with full-time work disability decreased from 37 to 13 (65%), and patients working part-time increased from 8 to 23 (65%). This change was already evident during the first year. CONCLUSION: Active vocational support in addition to DMARD treatment may prevent or delay work disability in patients with early RA.
16034454 Gene targeting by ribozyme against TNF-alpha mRNA inhibits autoimmune arthritis. 2005 Oct Ribozymes are catalytic RNA that bind and cleave specific regions of target RNA. Therefore, protein synthesis by the target RNA may be specifically inhibited by ribozymes. In this study, we have investigated if ribozymes possess therapeutic activity on inflammatory processes in vivo, as judged from effects on an arthritis model. A hammerhead ribozyme against TNF-alpha was designed and its catalytic activity in vitro was verified. The ribozyme was employed in vivo without any delivery system, as the plasmid-based ribozyme was taken up adequately by various tissues in mice by intravenous injection. The ability of the ribozyme to regulate the development of collagen-induced arthritis (CIA), a model largely dependent on TNF-alpha, was investigated. Systemic administration of the ribozyme to mice immunized with collagen type II in CFA significantly reduced the development of CIA. No effect was observed with a catalytically inactive variant of the ribozyme. Furthermore, the ribozyme efficiently blocked cartilage and bone destruction in the joints and ameliorated established CIA. These data demonstrate for the first time that gene targeting by a ribozyme to inactivate TNF-alpha in vivo is highly efficient in suppressing autoimmune arthritis, thus providing proof of concept that it may be used as therapeutic tool for TNF-alpha-dependent chronic inflammatory disorders.
16947382 Up-regulated transforming growth factor beta-inducible gene h3 in rheumatoid arthritis med 2006 Sep OBJECTIVE: To delineate the expression of transforming growth factor beta-inducible gene h3 (betaIG-H3) in rheumatoid synovitis and to determine the regulatory role of betaIG-H3 in the adhesion and migration of fibroblast-like synoviocytes (FLS). METHODS: Synovial tissue was obtained from patients with rheumatoid arthritis (RA) during joint replacement surgery, and FLS were isolated using enzymatic treatment. Immunohistochemical staining was performed to show the expression of betaIG-H3 within rheumatoid synovium. Synthesis of betaIG-H3 from FLS was determined by semiquantitative reverse transcription-polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Cell adhesion and migration assays were performed using the YH18 peptide in the fourth fas-1 domain of betaIG-H3 and function-blocking antibodies to integrins. RESULTS: Expression of betaIG-H3 was up-regulated in RA synovial tissue compared with synovial tissue from patients with osteoarthritis. FLS isolated from RA synovial tissue constitutively produced betaIG-H3, which was up-regulated by transforming growth factor beta1, interleukin-1beta, and tumor necrosis factor alpha. Although FLS expressed a variety of integrins, betaIG-H3 mediated adhesion and migration of FLS through interaction with alpha v beta3 integrin. Cytokines failed to affect the betaIG-H3-mediated adhesion. However, migration of FLS guided by betaIG-H3 was enhanced by interferon-gamma and platelet-derived growth factor type BB. The YH18 peptide in the fourth fas-1 domain of betaIG-H3 inhibited adhesion and migration in a dose-dependent manner. CONCLUSION: The results suggest that betaIG-H3, which is abundantly expressed in RA synovial tissue, plays a regulatory role in chronic destructive inflammation through the modulation of the adhesion and migration of FLS. This finding indicates the relevance of betaIG-H3 and alpha v beta3 integrin-interacting motifs as potential therapeutic targets in this disease.
16431346 BiP regulates autoimmune inflammation and tissue damage. 2006 Feb The endoplasmic reticulum chaperone BiP, in addition to its many important intracellular functions, has anti-inflammatory and immunomodulatory properties when present in the extracellular environment by the stimulation of an anti-inflammatory gene programme from human monocytes and by the development of T-cells that secrete regulatory cytokines such as interleukin-10 and interleukin-4. It can both prevent as well as treat ongoing collagen-induced arthritis. It is, therefore, a potential new biologic therapy for rheumatoid arthritis.
16257399 Review: Collagen markers in early arthritic diseases. 2006 Mar In arthritic diseases e.g. osteoarthritis (OA) and rheumatoid arthritis (RA), the stability of the collagen type II (CII) fibers, a major component of articular cartilage, is compromised with extensive proteolytic breakdown leading to cartilage erosion and joint deterioration. A clinical need for molecular markers that give instantaneous measure of rate of joint deterioration has developed, as other measurements e.g. arthroscopy, and joint space narrowing are insensitive to small changes in disease status over short periods of time. Owing to its exclusive presence in cartilaginous tissues, markers of CII synthesis and degradation have been extensively studied. Assays that measure these markers in biological fluids e.g. synovial fluid (SF), serum, and urine have been developed and applied to detect early disease onset, monitor disease progression, and response to anti-arthritic drugs. CII synthesis markers include the procollagen type II C-propeptide (PIICP) and the procollagen type IIA N-propeptide (PIIANP). CII degradation markers include CII C-telopeptide (CII-X), CII neoepitope (TIINE), helix II, C2C, CNBr 9.7, Coll 2-1, and Coll 2-1 NO(2). Most of these markers differentiate between early stages of OA, RA and reference controls. The best correlations with structural changes occur when measurements are made in SF while serum measurement frequently did not correlate with structural changes. Although the selection of an optimal marker or a set of markers is still problematic, few markers are of considerable utility in early detection and monitoring of arthritic diseases. The current challenge is to improve the discriminatory power of these markers so they can be used to guide therapeutic decisions.
17073674 Dissecting the genetic basis of rheumatoid arthritis in mouse models. 2006 Rheumatoid Arthritis, RA, is a common polygenic multi-factorial chronic inflammatory disorder that involves complex interactions between genetic and environmental factors. Despite major advances, the aetiology of the disease is still not completely understood. In this post-genome era, the sequencing of the human and some murine genomes as well as advances in global screening technologies offer an opportunity to accelerate the search for new pathological pathways and to identify new therapeutic targets. Animal models of RA offer an opportunity to dissect the genetic basis of disease in a simplified genome and controlled environment with the aim of identifying new pathological pathways and thus new therapeutic targets. Linkage analysis in the mouse model has identified more than 60 Loci, controlling disease phenotypes, immune response and cytokines. This indicates that gene variations among inbred mice strains affect the disease and that those polymorphic genes could be potential therapeutic targets. However, progress in identification of susceptibility genes in mouse models is slow. The progress is hampered by the complexity of disease as well as the traditional genetic dissection strategies. In this post-genome era, the sequencing of the human and some murine genomes as well as advances in global screening technologies offer an opportunity to accelerate the progress.
16102224 B-cell lymphoma of the larynx in a patient with rheumatoid arthritis. 2005 Aug We report a case of B-cell lymphoma with the larynx as the primary site of presentation in a rheumatoid arthritis patient previously treated with methotrexate. Primary non-Hodgkin's lymphoma (NHL) of the larynx is rare. There may be an increased risk of lymphoma in patients with rheumatoid arthritis, with an even higher risk in those patients treated with methotrexate. The diagnostic and treatment options are discussed.
16409309 Access to tumour necrosis factor inhibitors for rheumatoid arthritis treatment under the A 2006 Jan BACKGROUND: Access to tumour necrosis factor inhibitors (TNFI) for the treatment of rheumatoid arthritis under the Australian Pharmaceutical Benefits Scheme (PBS) is governed by a set of arrangements, operational from August 2003. Patients must meet strict criteria for both starting and continuing TNFI. Examination of utilization data is important for assessing the broader implications of arrangements for access to expensive pharmaceuticals under schemes such as the PBS. AIM: To examine the uptake of TNFI over the first year of subsidized availability of etanercept under the PBS, and to compare these data to the predicted utilization and expenditure. METHODS: Collection and analysis of prescription and expenditure data for the three listed TNFI: etanercept, infliximab and adalimumab processed under the PBS for the period August 2003 to July 2004. RESULTS: A total of 8,053 prescriptions for TNFI was reimbursed at a total cost of 15.2 m Australian dollars. The total PBS expenditure on etanercept was just over 14 m Australian dollars, 14% of the predicted annual expenditure. The relative per capita uptake of etanercept was highest in the Australian Capital Territory and lowest in the Northern Territory. More than 50% of prescriptions for etanercept were for concessional patients (7.3 m Australian dollars). CONCLUSION: Prescription rates and expenditure on etanercept were substantially below those forecast over the first year. There are opportunities to adjust the PBS restrictions for subsidized access to TNFI to benefit more patients.
16380755 [Prevalence of rheumatoid arthritis in North Sardinia: the Tempio Pausania's study]. 2005 Dec OBJECTIVE: To estimate the prevalence of rheumatoid arthritis in an Italian general population. METHODS: The study was conducted in the years 2002-2003 in Tempio Pausania's health district located on the North Sardinia and involved 30264 subjects aged 18 years or more treated by 29 general practices (GP). The GP was contact first by phone and letter and secondly a Rheumatologist administered a structured interview that included a screening questionnaire for RA. Cases were defined by the 1987 American College of rheumatology criteria adapted to epidemiological surveys. Every cases were examined by Rheumatologist and General practices together. The age and sex distribution of the sample were similar to those of the Italian population from the 2001 census. RESULT: Of the 141 subjects who fulfilled the inclusion criteria, there were 113 women and 28 men, with a mean age at diagnosis of 45 years. The prevalence of RA was 0,46% in the general population, 0,73% in women and 0,19% in men. CONCLUSION: Our results suggest that the prevalence of RA is comparable to that reported in other Mediterranean countries. Women are more affected than men. Our prevalence is higher than that observed in Chiavari in 1992.
16343797 Atypical lymphoplasmacytic and immunoblastic proliferation from rheumatoid arthritis: a ca 2006 A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented rheumatoid arthritis (RA) is presented. A 68-year-old Japanese female with a 6-year history of RA presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed paracortical hyperplasia and numerous lymphoid follicles. On high-power field, the paracortical area was diffusely infiltrated by a polymorphous population consisting of numerous mature plasma cells, plasmacytoid cells, immunoblasts, including Hodgkin-like cells, small- to medium-sized lymphocytes, and histiocytes. Immunohistochemical study demonstrated that immunoblasts usually were CD20+, and a portion of them was CD30+. The histomorphological findings of the present case are similar to those of methotrexate (MTX)-induced atypical lymphoproliferative disorders (LPDs) in some aspects. However, Epstein-Barr virus-encoded small RNA-positive cells were not identified by in situ hybridization. The polytypic nature of B lymphocytes also was demonstrated by immunohistochemistry and polymerase chain reaction. Moreover, there was no history of MTX therapy in the present case, indicating that MTX-induced, LPD-like ALPIB may occur even in the RA patients not treated with MTX therapy.
16052582 Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: tw 2005 Aug OBJECTIVE: To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA-4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy. METHODS: This was a 12-month, multicenter, randomized, double-blind, placebo-controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial. RESULTS: A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted. CONCLUSION: Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.
16313352 Rheumatic diseases: the effects of inflammation on bone. 2005 Dec Rheumatoid arthritis, juvenile idiopathic arthritis, the seronegative spondyloarthropathies including psoriatic arthritis, and systemic lupus erythematosus are all examples of rheumatic diseases in which inflammation is associated with skeletal pathology. Although some of the mechanisms of skeletal remodeling are shared among these diseases, each disease has a unique impact on articular bone or on the axial or appendicular skeleton. Studies in human disease and in animal models of arthritis have identified the osteoclast as the predominant cell type mediating bone loss in arthritis. Many of the cytokines and growth factors implicated in the inflammatory processes in rheumatic diseases have also been demonstrated to impact osteoclast differentiation and function either directly, by acting on cells of the osteoclast-lineage, or indirectly, by acting on other cell types to modulate expression of the key osteoclastogenic factor receptor activator of nuclear factor (NF) kappaB ligand (RANKL) and/or its inhibitor osteoprotegerin (OPG). Further elucidation of the mechanisms responsible for inflammation-induced bone loss will potentially lead to the identification of novel therapeutic strategies for the prevention of bone loss in these diseases. In this review, we provide an overview of the cell types, inflammatory mediators, and mechanisms that are implicated in bone loss and new bone formation in inflammatory joint diseases.
16406300 Serum insulin-like growth factor-axis and matrix metalloproteinases in patients with rheum 2006 May BACKGROUND: Insulin-like growth factor (IGF)-I plays an important role for maintaining cardiac functions. We clarified the unknown role of IGF-axis in rheumatic heart disease (RHD). METHOD: Interleukin (IL)-10, growth hormone (GH), IGF, IGF binding protein (IGFBP)-3 and matrix metalloproteinase (MMP) were measured by ELISA and zymography in 30 age range-matched normal subjects (control), 36 patients with acute phase of rheumatoid arthritis (RA) with positive rheumatoid factor (RF) and C-reactive protein (CRP), and in 43 patients with RHD with negative RF and CRP. RESULT: Compared with normal subjects, increased IL-10 level and decreased GH were found in RA group whereas unchanged IL-10 and decreased GH were found in RHD group. Compared with age range-matched normal subjects, decreased IGFBP-3, MMP-9 levels, unchanged IGF-I were found in RA group whereas decreased IGF-I levels, unchanged IGFBP3 and increased MMP-9 at age>30 years were found in RHD group. IGF-II was not changed in RA and RHD groups. CONCLUSION: These findings may imply that during inflammatory phase, the levels of anti-inflammation was high and total IGF-I and IGF bioavailability were maintained in patients with RA. Our findings in RHD may speculate that the long-term reduction of GH and IGF-I as well as the compensating effects of upregulated MMP-9 activity may be partially involved in the long-term pathogenesis from RHD to heart failure. Decreased GH, decreased IGF-I and increased MMP-9 activities may be possible diagnostic markers in RHD for developing heart failure.
16868975 Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients wi 2006 Aug OBJECTIVE: Women with systemic lupus erythematosus (SLE) have a 7-50-fold increased risk of coronary artery disease (CAD). In the general population, oxidized low-density lipoprotein (ox-LDL) increases the risk for CAD. Normal high-density lipoproteins (HDLs) protect LDL from oxidation; proinflammatory HDLs do not. This study was undertaken to determine whether patients with SLE, who have chronic inflammation that causes oxidative damage, have more proinflammatory HDL and higher levels of ox-LDL, thus predisposing them to atherosclerosis. METHODS: One hundred fifty-four women with SLE, 48 women with rheumatoid arthritis (RA), and 72 healthy controls were studied. The ability of the patients' HDL to prevent oxidation of normal LDL was measured. Values >1.0 (the value assigned for LDL oxidation in the absence of HDL) after the addition of HDL indicated proinflammatory HDL. Plasma ox-LDL levels were measured as the amount of oxidation produced by the patient's LDL after the removal of HDL. RESULTS: SLE patients had more proinflammatory HDL (mean +/- SD score 1.02 +/- 0.57, versus 0.68 +/- 0.28 in controls [P < 0.0001] and 0.81 +/- 0.22 in RA patients [P = 0.001 versus SLE patients]). A higher proportion of SLE patients had proinflammatory HDL: 44.7% of SLE patients versus 4.1% of controls and 20.1% of RA patients had scores >1.0 (P < 0.006 between all groups). Levels of ox-LDL correlated with levels of proinflammatory HDL (r = 0.37, P < 0.001). SLE patients with CAD had significantly higher proinflammatory HDL scores than patients without CAD (P < 0.001). CONCLUSION: HDLs are proinflammatory in a significant proportion of SLE patients and are associated with elevated levels of ox-LDL. Abnormal HDLs impair the ability to prevent LDL oxidation and may predispose to atherosclerosis.
15130899 A good response to early DMARD treatment of patients with rheumatoid arthritis in the firs 2005 Jan OBJECTIVE: To describe the frequency and duration of remission in the Utrecht rheumatoid arthritis cohort of patients followed since diagnosis, and the clinical and treatment characteristics of patients with remission v those without. METHODS: In 1990 the Utrecht rheumatoid arthritis cohort study group started a clinical trial in which patients with recent onset of rheumatoid arthritis (<1 year) were randomised into four treatment groups: hydroxychloroquine (n = 169); intramuscular gold (n = 163); methotrexate (n = 166); and pyramid (n = 64). After two years, rheumatologists were allowed to prescribe any disease modifying antirheumatic drug. Remission was defined as: duration of morning stiffness < or =15 min, mean VAS pain < or =10 mm, Thompson joint score < or =10, and ESR < or =30 mm/h during at least six months. Cox regression analysis was used to determine baseline clinical, demographic, and treatment predictors of remission. RESULTS: Mean follow up duration was 62 months. Thirty six per cent achieved at least one period of remission. Median duration between diagnosis and the first remission period was 15 months for the intramuscular gold group, 18 months for the methotrexate and hydroxychloroquine groups, and 24 months for the pyramid group (NS). Predictors of remission were early response to initial treatment, less pain, rheumatoid factor negativity, and lower joint score at baseline. CONCLUSIONS: After a mean follow up duration of 62 months, only 36% of the patients had fulfilled the remission criteria at least once. A good response to treatment during the first year seems to be independently associated with remission rather than initial treatment alone.