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ID PMID Title PublicationDate abstract
19767659 Where the immune response meets the vessel wall. 2009 Sep Immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis and spondyloarthritis, are associated with increased cardiovascular morbidity and mortality, independent of the established cardiovascular risk factors. The chronic inflammatory state, a hallmark of IMIDs, is considered to be a driving force for accelerated atherogenesis. Consequently, aggressive control of disease activity has been suggested to be instrumental for cardiovascular risk reduction. Specific guidelines for cardiovascular risk reduction in patients with IMIDs, particularly rheumatoid arthritis, are lacking, largely due to the absence of randomised clinical trial data. In this review, we focus on pathophysiology and observational evidence of cardiovascular risk in different prototypes of IMIDs.
21144590 The potential role of VPREB1 gene copy number variation in susceptibility to rheumatoid ar 2011 Jun Although the etiology of rheumatoid arthritis (RA) remains unknown, it has been widely suggested that RA has a genetic background. In humans, a copy number loss of 22q11.2, a region harboring the VPREB1 gene, has been suggested to be associated with several immunologic disorders, but there has been no study on the copy number variation (CNV) of the VPREB1 and its potential association with RA. Here, we explored the association between the RA and the CNV of the VPREB1 gene by performing genomic quantitative PCR and quantification of B cell subsets in RA patients and controls. The proportion of the individuals with <2 copies of the VPREB1 gene was significantly higher in the patient group than that in the controls (12.9% vs 0.9%, p<0.0001), while that of the individuals with >2 copies was lower in the patient group than that in the controls (1.7% vs 18.9%, p<0.0001). The odds ratio (OR) of the individuals with <2 copies was significantly higher compared with the odds ratio of those individuals with 2 copies (OR=12.1, 95% confidence interval (CI) 2.8-51.6). Likewise, the OR of the individuals with >2 copies was significantly lower than the OR of those individuals with 2 copies (OR=0.09, 95% CI 0.03-0.3). We also found that the proportion of CD21⁻CD23⁻ B cells was significantly higher in the RA patients compared with that of the controls (11.9% vs 5.7%, p=0.002), but the proportion of CD21+CD23+ cells was significantly lower in the RA patients (26.2% in RA vs 34.9% in the controls, p=0.005). To the best of our knowledge, this is the first evidence showing the association between a low copy number of the VPREB1 gene and RA, and this may help understanding the pathogenesis of RA and other autoimmune disorders.
19653057 Rheumatoid nodulosis: successful response to topical tacrolimus. 2009 Nov Rheumatoid nodulosis is considered a benign variant of rheumatoid arthritis. Several therapies have been used with variable results. We report a 63-year-old man who presented with nodular lesions on the metacarpophalangeal joints and knees which were diagnosed of rheumatoid nodulosis. Topical tacrolimus was started with good response on the following months.
19565493 Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis. 2009 Jul OBJECTIVE: Obesity protects against radiographic joint damage in rheumatoid arthritis (RA) through poorly defined mechanisms. Adipocytokines are produced in adipose tissue and modulate inflammatory responses and radiographic joint damage in animal models. The purpose of this study was to examine the hypothesis that adipocytokines modulate inflammation and radiographic joint damage in patients with RA. METHODS: We compared serum concentrations of leptin, resistin, adiponectin, and visfatin in 167 RA patients and 91 control subjects. The independent association between adipocytokines and body mass index (BMI), measures of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNFalpha]), and radiographic joint damage (Larsen score; n = 93 patients) was examined in RA patients by multivariable regression analysis first controlling for age, race, and sex, and then for obesity (BMI) and inflammation (TNFalpha, IL-6, and CRP). RESULTS: Concentrations of all adipocytokines were significantly higher in RA patients than in controls; for visfatin and adiponectin, this association remained significant after adjusting for BMI, inflammation, or both. Visfatin concentrations were associated with higher Larsen scores, and this association remained significant after adjustment for age, race, sex, disease duration, BMI, and inflammation (odds ratio [OR] 2.38 [95% confidence interval (95% CI) 1.32-4.29], P = 0.004). Leptin concentrations showed a positive association with the BMI (rho = 0.58, P < 0.01) and showed a negative association with the Larsen score after adjustment for inflammation (OR 0.32 [95% CI 0.17-0.61], P < 0.001), but not after adjustment for BMI (OR 0.86 [95% CI 0.42-1.73], P = 0.67). CONCLUSION: Concentrations of adipocytokines are increased in patients with RA and may modulate radiographic joint damage. Visfatin is associated with increased, and leptin with reduced, levels of radiographic joint damage.
19342959 Autonomic dysfunction in fibromyalgia assessed by the Composite Autonomic Symptoms Scale ( 2009 Jun BACKGROUND: It has been suggested that autonomic nervous system dysfunction may explain all of fibromyalgia (FM) multisystem features. Such proposal is based mostly on the results of diverse heart rate variability analyses. The Composite Autonomic Symptom Scale (COMPASS) is a different validated method to recognize dysautonomia. OBJECTIVES: The main objective of our study was to investigate symptoms of autonomic dysfunction in FM patients by means of COMPASS. A secondary objective was to define whether there is a correlation between COMPASS and Fibromyalgia Impact Questionnaire (FIQ) scores in FM patients. METHODS: Design, analytical cross-sectional study. Our study population included 3 different groups of women: 30 patients with FM, 30 patients with rheumatoid arthritis, and 30 women who considered themselves healthy. All participants filled out COMPASS and FIQ questionnaires. RESULTS: FM patients had significantly higher values in all COMPASS domains. COMPASS total score (54.6 +/- 20.9; mean +/- standard deviation) clearly differentiated FM patients from the other 2 groups (21.6 +/- 16.5 and 9.5 +/- 10.2, respectively). P < 0.0001. The majority of FM patients gave affirmative answers to questions related to orthostatic, digestive, sleep, sudomotor, or mucosal dysfunction. There was a significant correlation between COMPASS and FIQ scores (Spearman r = 0.5, P < 0.005). CONCLUSIONS: Patients with FM have multiple nonpain symptoms related to different expressions of autonomic dysfunction. There is a correlation between a questionnaire that measures FM severity (FIQ) and an autonomic dysfunction questionnaire (COMPASS). Such correlation suggests that autonomic dysfunction is inherent to FM.
20693259 Numbers of CD25+Foxp3+ T cells that lack the IL-7 receptor are increased intra-articularly 2010 Nov OBJECTIVES: To investigate numbers and function of CD25(+) regulatory T cells (Tregs) that lack IL-7 receptor (CD127) expression in RA. METHODS: Numbers of CD4 T cells expressing either CD25 or CD127, and those co-expressing or lacking both CD25 and CD127 were assessed in peripheral blood (PB) of RA patients and healthy controls, and in paired samples of SF and PB from RA patients. All T-cell subsets were analysed for FoxP3 expression. The anergic state and the capacity to suppress CD127(+) proliferating responder T cells were determined. RESULTS: Numbers of CD127(-) T cells and CD25(+) Tregs in PB of RA patients were not different from controls but significantly increased in SF compared with PB. CD25(+) and CD127(-) T cells showed comparable FoxP3 expression. CD127(+) T cells hardly expressed FoxP3. PB CD25(+)CD127(-) T cells identified a subset that consisted for 75% of FoxP3(+) cells. SF CD25(+)CD127(-) T-cell number was increased; however, in SF fewer of these cells were FoxP3(+). CD25(+)CD127(-) T cells were anergic, and in controls potent suppressors of CD127(+) proliferating T cells, but in RA patients these cells showed impaired suppression. In line with this, IL-7 had an increased capacity to activate total CD4 T cells from SF as compared with PB despite increased numbers of CD25(+)CD127(-) in SF. CONCLUSIONS: These data demonstrate improved identification of FoxP3(+) T cells in RA patients by the absence of CD127 in addition to CD25 expression. Increased numbers of CD25(+)CD127(-) T cells are found in inflamed RA joints, but they have an impaired suppressive function, which could contribute to the persistent arthritis in these patients.
19333642 Rheumatoid cachexia, central obesity and malnutrition in patients with low-active rheumato 2009 Aug BACKGROUND AND AIMS: The concurrent decrease in fat free mass (FFM) and increase in fat mass (FM), including central obesity, in patients with rheumatoid arthritis (RA) may be related to increased cardiovascular morbidity as well as to functional decline. The objectives of this study were to evaluate body composition and nutritional status in patients with RA and the feasibility of bioelectrical impedance (BIA) to detect rheumatoid cachexia. METHODS: Eighty RA outpatients (76% women), mean age 61 (range 22-80) years and with mean disease duration of 6 (range 1-52) years, were assessed by body mass index (BMI), waist circumference (WC), whole-body dual-energy X-ray absorptiometry (DXA), BIA and the Mini Nutritional Assessment (MNA). RESULTS: Fat free mass index (FFMI; kg/m(2)) was low in 26% of the women and in 21% of the men. About every fifth patient displayed concomitant low FFMI and elevated fat mass index (FMI; kg/m(2)), i.e. rheumatoid cachexia. BMI and MNA were not able to detect this condition. Sixty-seven percent had increased WC. Reduced FFM was independently related to age (p = 0.022), disease duration (p = 0.027), ESR (p = 0.011) and function trendwise (p = 0.058). There was a good relative agreement between DXA and BIA (FM r (2) = 0.94, FFM r (2) = 0.92; both p < 0.001), but the limits of agreement were wide for each variable, i.e. for FM -3.3 to 7.8 kg; and for FFM -7.9 to 3.7 kg. CONCLUSION: Rheumatoid cachexia and central obesity were common in patients with RA. Neither BMI nor MNA could detect this properly. There was a good relative agreement between DXA and BIA, but the limits of agreement were wide, which may restrict the utility of BIA in clinical practice.
20831776 The Belgian MIRA (MabThera In Rheumatoid Arthritis) registry: clues for the optimization o 2010 INTRODUCTION: This study describes the results of the Belgian 'MabThera In Rheumatoid Arthritis (MIRA)' registry: effectiveness, safety and evaluation of the current retreatment practice on the background of the Belgian reimbursement criteria for rituximab. METHODS: All Belgian rheumatologists had the possibility to participate in the study. Patients entered the registry in November 2006 and the entry is still open. RESULTS: By mid-September 2009, 401 patients had entered the registry with a mean follow-up time of 70 weeks. Overall, DAS28-ESR decreased from 6.0 at baseline to 4.2 at week 16. Further decrease of disease activity was observed at the end of year 1 and year 2 with mean DAS28-ESR of 4.0 and 3.7 at these respective time points. More than 80% of patients showed a EULAR response at week 16. Patients could be retreated if they had DAS scores of > 3.2 at least 6 months after the previous course. Second and third courses were given in 224 and 104 patients, respectively. At month 6 after the second course, significantly lower DAS28-ESR values were observed compared to the first course. This was especially the case for patients who were retreated before they showed an obvious flare (DAS increase > 1.2). CONCLUSIONS: This study describes the follow-up of a daily clinical practice cohort of 401 RA patients with long-standing refractory disease treated with rituximab. Relatively high DAS28 values at the start of each retreatment, compared to values 6 months after each treatment course, were noted. Moreover, further decrease of DAS28 scores after the second course was significantly more pronounced in those patients who didn't show an obvious flare. These two elements suggest that treatment of RA patients with rituximab could be optimized by earlier retreatment.
19727735 Rheumatoid-like deformities in Parkinson's disease with 1-year follow-up: case report and 2010 Sep Rheumatoid-like deformities in joints are uncommon in patients with Parkinson's disease and easy to be misdiagnosed with rheumatoid arthritis. Therefore, unnecessary treatment is often initiated. Here, we report a case of a 60-year-old woman with Parkinson's disease developing a rheumatoid-like joint deformities, and evaluate 1-year follow-up outcome. We also review the literature and discuss the clinical characteristics, possible pathogenesis, and treatment strategy of these cases.
20074281 Rilonacept--CAPS and beyond. 2009 Dec Rilonacept is a dimeric fusion protein consisting of the extracellular domains of interleukin (IL)-1 type 1 receptor and IL-1 receptor accessory protein joined to the constant region (Fc) of human immunoglobulin G1. By incorporating both components of the IL-1 binding complex, rilonacept is able to tightly bind IL-1 with picomolar affinity. Although early clinical results in rheumatoid arthritis (RA) suggested that RA is not primarily an IL-1-driven disease, the discovery that the rare genetic conditions called cryopyrin-associated periodic syndromes (CAPS) were caused by overproduction of IL-1 led to clinical development and approval for these conditions. An assay that detects rilonacept:IL-1 complexes in plasma is helping to identify new indications, such as gout, in which IL-1 overproduction plays a key pathogenic role. The development of rilonacept for CAPS was achieved through collaboration between the pharmaceutical industry, academia, and government agencies, and demonstrates that knowledge gleaned in orphan indications can inform drug development for more common and heterogeneous diseases.
20886247 Impact of tight control strategy on rheumatoid arthritis in Sarawak. 2011 May The aim of our study is to describe the impact of tight control strategy on the care of RA patients in Sarawak General Hospital. We performed a prospective study of all patients with a diagnosis of RA who received treatment at the Rheumatology Clinic in Sarawak General Hospital over a 1-year period. Systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS 28-ESR <2.6) were carried out in the clinic over the 1-year period. Disease activity and treatment regimes of all 142 patients were collected for at baseline and 1 year later for statistical analysis. Our patients have a significantly lower DAS 28 with a mean of 2.99 ± 0.95 compared with baseline of 4.31 ± 1.34 (p < 0.000). More patients were in remission 1 year later compared to baseline (36.6% vs 11.3%). Tight control strategy has a positive impact on the care of RA patients in our centre. By optimising the care of RA through tight control strategy, RA can be better controlled in our centre.
19337285 Management of cardiovascular disease risk in chronic inflammatory disorders. 2009 Apr Patients with chronic inflammatory disorders are at increased risk of developing premature cardiovascular disease. Despite significant advances in our understanding of the effects of inflammatory pathways on the vasculature, clear guidelines on the management of traditional and nontraditional cardiovascular risk factors in patients with systemic autoimmunity are lacking. Thus, rigorous studies assessing the individual contributions of the various treatments used in autoimmune disorders, as well as their effects on atherosclerosis development in these conditions, are needed. Furthermore, effective screening methods are needed to identify those patients with inflammatory disease who are at the highest risk for atherosclerotic complications, and who would benefit from early intervention. There is a clear need for a unifying explanation of the factors that promote premature cardiovascular disease in patients with chronic inflammatory disorders. Nevertheless, ongoing advances in the understanding of immune-mediated vascular damage mean that we are edging closer to the development of disease-specific preventive strategies to ameliorate or abrogate premature cardiovascular disease in these patients.
19213235 Infectious complications in patients with psoriasis and rheumatoid arthritis treated with 2009 Feb Treatment of patients with moderate-severe psoriasis and/or psoriatic arthritis includes systemic biologic, antimetabolite, and immunosuppressive therapy. However, adverse events such as serious infectious complications must be considered before starting therapy and throughout treatment. The authors describe the case of a male on combination etanercept and methotrexate for psoriasis and psoriatic arthritis for years who developed a spontaneous epidural abscess with resulting quadriplegia. In addition, a review of the literature was performed looking at the risk of serious infectious complications with antitumor necrosis factor (anti-TNF) monotherapy or combination therapy with methotrexate fro the treatment of psoriasis and rheumatoid arthritis. Serious infectious risk does not appear to be increased with etanercept or other anti-TNF agents either alone or in combination with methotrexate. Nevertheless, clinicians are cautioned to carefully weigh the risks and benefits of treating with anti-TNF agents in patients who are prone to infection.
20472598 IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF the 2010 Sep OBJECTIVES: Interleukin 33 (IL-33) is a new member of the IL-1 family of cytokines which signals via its receptor, ST2 (IL-33R), and has an important role in Th2 and mast cell responses. This study shows that IL-33 orchestrates neutrophil migration in arthritis. METHODS AND RESULTS: Methylated bovine serum albumin (mBSA) challenge in the knee joint of mBSA-immunised mice induced local neutrophil migration accompanied by increased IL-33R and IL-33 mRNA expression. Cell migration was inhibited by systemic and local treatments with soluble (s)IL-33R, an IL-33 decoy receptor, and was not evident in IL-33R-deficient mice. IL-33 injection also induced IL-33R-dependent neutrophil migration. Antigen- and IL-33-induced neutrophil migration in the joint was dependent on CXCL1, CCL3, tumour necrosis factor alpha (TNFalpha) and IL-1beta synthesis. Synovial tissue, macrophages and activated neutrophils expressed IL-33R. IL-33 induces neutrophil migration by activating macrophages to produce chemokines and cytokines and by directly acting on neutrophils. Importantly, neutrophils from patients with rheumatoid arthritis successfully treated with anti-TNFalpha antibody (infliximab) expressed significantly lower levels of IL-33R than patients treated with methotrexate alone. Only neutrophils from patients treated with methotrexate alone or from normal donors stimulated with TNFalpha responded to IL-33 in chemotaxis. CONCLUSIONS: These results suggest that suppression of IL-33R expression in neutrophils, preventing IL-33-induced neutrophil migration, may be an important mechanism of anti-TNFalpha therapy of inflammation.
19830929 [Health-related quality of life and chronic pain experience in rheumatic diseases]. 2009 Jul OBJECTIVES: To assess differences among health-related quality of life, pain threshold and perception,and passive coping strategies with chronic pain(specifically retreating, worrying, and resting), as well as associations among variables in three groups of rheumatic patients - fibromyalgia (FM),rheumatoid arthritis (RA), and osteoarthritis (OA). MATERIAL AND METHODS: 86 participants diagnosed with FM (n = 25), RA (n = 31) and OA (n = 30) completed the following measures: Clinical and Sociodemographic Questionnaire (QSDC), Medical Outcomes Study 36-item Short Form Health Survey(SF-36v2), Pain Coping Inventory (PCI), visual analogic scale (VAS) for pain, and dolorimeter for threshold pain. SPSS software was used to perform statistical analyses. RESULTS: FM patients reported the lowest levels of quality of life and threshold pain, as well as the highest levels of pain perception and passive coping with chronic pain. Associations between variables support that experience with chronic pain is managed more successfully in OA patients, followed by RA patients and, finally, by FM patients. CONCLUSIONS: Our findings support the adoption ofa biopsychosocial model for assessment and intervention with rheumatic patients, considering specificities associated to each illness.
18957482 Perinatal characteristics, early life infections and later risk of rheumatoid arthritis an 2009 Jul OBJECTIVES: To investigate the importance of birth characteristics and early life infections on the risk of later rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). METHODS: A nationwide register-based case-control study was performed based on prospectively recorded data on individuals born in 1973 or later. Using the Swedish inpatient register and the early arthritis register, cases with RA aged 16 years or above (n = 333) and JIA (n = 3334) were identified. From the Swedish medical birth register (MBR), four controls per case, matched by sex, year and delivery unit were randomly selected. Through linkage to the MBR and to the Swedish inpatient register information on maternal, pregnancy and birth characteristics and infections during the first year of life was identified. Univariate and multivariate odds ratios (OR) were calculated using conditional logistic regression. RESULTS: Overall, infections during the first year of life were associated with increased risks for seronegative (OR 2.6, 95% CI 1.0 to 7.0) but not seropositive (OR 1.2) RA and for JIA (OR 1.9, 95% CI 1.7 to 2.1). Low birth weight (OR 0.7) and being small for gestational age (OR 0.5) were associated with reduced risks of RA of borderline statistical significance. Preterm birth (gestational age < or =258 days) was associated with a non-significantly decreased risk of RA (OR 0.6). Large for gestational age (OR 1.6) and having more than three older siblings (OR 1.4) were non-significantly associated with the risk of RA. CONCLUSION: Infections during the first year of life, and possibly also factors related to fetal growth and timing of birth, may be important in the aetiologies of adult RA and JIA.
20208415 Evaluating the role of rheumatoid factors for the development of rheumatoid arthritis in a 2010 Mar Enzyme-linked immunosorbent assays (ELISA) have been widely used to determine quantitatively autoantibodies. However, the processes for the purification and immobilization of antigens in conventional ELISA methods include multiple steps, which have hampered the application for screening of autoantibodies. Here, we have developed a novel ELISA system using the plates pre-coated with glutathione casein to capture recombinant proteins fused to N-terminal glutathione S-transferase (GST). The GST-fused proteins were synthesized with the wheat germ cell-free protein production system. Thus, the present system combined the GST-capture ELISA with the cell-free protein production system, which allowed immobilization of the recombinant proteins with one-step purification. Using this ELISA method, we determined whether rheumatoid factors (RF), which have been considered as one of the representative disease-specific autoantibodies for rheumatoid arthritis (RA), were genetically associated with severity of arthritis in a mouse model for RA, MRL/Mp-lpr/lpr (MRL/lpr). GST-fused human IgG1-Fc (GST-Fc), synthesized with the robotic protein synthesizer, were used as reactants for RF. Serum samples for RF were prepared from 11 lines of a recombinant inbred mouse strain, MXH/lpr, which was established from intercrosses between MRL/lpr and non-arthritic C3H/HeJ-lpr/lpr (C3H/lpr) strains, composed of a different genomic recombination derived from the parental strains in each line. A correlation of RF titers with the severity of the arthritis in these lines was not significant, indicating genetic dissociation of RF from arthritis and that RF is not necessarily required for the development of RA. The present method may provide high-throughput screening for determining the disease-specific autoantibodies in autoimmune diseases.
20871130 Perceptions of the effects of exercise on joint health in rheumatoid arthritis patients. 2010 Dec OBJECTIVES: Exercise is important in RA management. However, RA patients are less active than the general population. This qualitative study explores the perceptions of patients regarding the effects of exercise on joint health. METHODS: A purposive sample of 12 female and 6 male RA outpatients [age: 23-76 years; disease duration: 2.5 months to 33 years; HAQ score: 0-2.13] participated in four moderated focus groups. The main questions addressed were: (i) How do you feel exercise affects your joints?; and (ii) What affects your exercise behaviour? Transcriptions were independently analysed with 455 meaning units identified. An inductive, thematic analysis was conducted using established techniques. Discussion with a third analyst contributed to consensus validation. RESULTS: Sixteen constructs emerged, clustering into five themes, reflecting the issues relating to exercise and joint health in RA patients. Emergent themes were: 'health professionals showing a lack of exercise knowledge', 'not knowing what exercise should be done', 'worry about causing harm to joints', 'not wanting to exercise as joints hurt' and 'having to exercise because it is helpful'. CONCLUSIONS: RA patients demonstrated awareness of the advantages of exercise for their joints, both experientially and through education. However, they perceived that health professionals lacked certainty and clarity regarding specific exercise recommendations and the occurrence of joint damage. Thus, to enhance patient-centred exercise prescription in the RA population, uncertainties surrounding joint health, pain symptoms and exercise specificity need to be addressed, alongside continual emphasis of exercise benefits.
20488785 Carbamylation-dependent activation of T cells: a novel mechanism in the pathogenesis of au 2010 Jun 15 The posttranslational modification of proteins has the potential to generate neoepitopes that may subsequently trigger immune responses. The carbamylation of lysine residues to form homocitrulline may be a key mechanism triggering inflammatory responses. We evaluated the role of carbamylation in triggering immune responses and report a new role for this process in the induction of arthritis. Immunization of mice with homocitrulline-containing peptides induced chemotaxis, T cell activation, and Ab production. The mice also developed erosive arthritis following intra-articular injection of peptides derived from homocitrulline and citrulline. Adoptive transfer of T and B cells from homocitrulline-immunized mice into normal recipients induced arthritis, whereas systemic injection of homocitrulline-specific Abs or intra-articular injection of homocitrulline-Ab/citrulline-peptide mixture did not. Thus, the T cell response to homocitrulline-derived peptides, as well as the subsequent production of anti-homocitrulline Abs, is critical for the induction of autoimmune reactions against citrulline-derived peptides and provides a novel mechanism for the pathogenesis of arthritis.
19074911 The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who und 2009 Nov OBJECTIVE: To assess the safety, tolerability and efficacy of abatacept in patients with rheumatoid arthritis (RA) who had failed anti-tumour necrosis factor (TNF) therapy and were switched to abatacept directly or after completing washout. METHODS: In this international, 6-month, open-label trial, patients had active RA, an inadequate response to anti-TNF therapy for 3 months or longer and a disease activity score in 28 joints (DAS28 (C-reactive protein; CRP) of 5.1 or greater. "Washout" patients discontinued anti-TNF therapy 2 months or longer pre-screening; "direct-switch" patients began abatacept ( approximately 10 mg/kg) at their next scheduled anti-TNF therapy dose. RESULTS: 1046 patients were treated (449 washout, 597 direct-switch; baseline characteristics were similar between groups). At 6 months, adverse events (AE; 78.0% vs 79.2%), serious AE (11.1% vs 9.9%) and discontinuations due to AE (3.8% vs 4.0%) and serious AE (2.0% vs 1.3%) were comparable in washout versus direct-switch patients. There were no opportunistic infections. At 6 months, in washout versus direct-switch patients, similar clinically meaningful improvements were seen in DAS28 (CRP) (> or =1.2 unit improvement, 59.5% vs 53.6%, respectively; low disease activity state, 22.5% vs 22.3%; DAS28-defined remission, 12.0% vs 13.7%), physical function (health assessment questionnaire disability index > or =0.22 improvement; 46.3% vs 47.1%) and health-related quality of life (mean change in short-form 36 scores: physical component summary, 5.5 vs 6.1; mental component summary, 4.8 vs 5.4). CONCLUSION: Abatacept demonstrated acceptable safety and tolerability and clinically meaningful efficacy over 6 months in patients with inadequate response to anti-TNF therapy. Results were comparable with or without a washout, supporting direct switching from anti-TNF therapy to abatacept as an option in clinical practice. TRIAL REGISTRATION NUMBER: NCT00124982.