Browse

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

ID PMID Title PublicationDate abstract
19419639 [Costs of biological treatment of rheumatoid arthritis]. 2009 May 4 INTRODUCTION: Biological drugs are used for the treatment of severe rheumatoid arthritis (RA). The high costs of such treatment have drawn attention to the economic appropriateness of the use of biological drugs. There are no Danish studies of the real costs of present clinical practice. The purpose of this study was to compare the actual costs of RA treatment for the three most commonly used biological drugs. MATERIAL AND METHODS: Data were collected from three Danish hospitals. The study is a cost analysis designed as a retrospective cohort study using data from medical records (n = 198). RESULTS: The costs of infliximab varied due to dose escalation from 78,660 DKK at one hospital to 120,657 DKK at another hospital. Treatment with either etanercept or adalimumab will tend to cost the same as or less than treatment with infliximab, when infliximab doses exceed the standard dose (3 mg/kg), and treatment breaks amount to at least 10%. At one hospital treatment breaks reduced the consumption of etanercept and adalimumab by 20%. CONCLUSION: Actual medicine expenses for treatment of RA with infliximab, etanercept and adalimumab tend to be equal. Consequently, there is no economic rationale for basing the choice of drug on costs calculated on the basis of standard dosage. Instead, the choice should be based on considerations of efficacy, safety, patient needs and the treatment feasibility.
19854709 iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel infla 2010 Apr OBJECTIVE: To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders. METHODS: Sera obtained from rheumatoid arthritis (RA) patients before and after anti-TNF therapy were analysed by iTRAQ (isobaric tags for relative and absolute quantitation) quantitative proteomic analysis and further validated by ELISA. RESULTS: Of 326 proteins identified by proteomic analysis, increased serum levels of leucine-rich alpha-2 glycoprotein (LRG) was identified in RA patients before therapy. Serum LRG concentrations were significantly elevated in RA patients compared with healthy controls and decreased after anti-TNF therapy. Furthermore, serum LRG concentrations correlated with disease activity in RA and Crohn's disease (CD). Interestingly, in a subpopulation of patients with active CD and normal C-reactive protein levels, serum LRG concentrations were elevated. CONCLUSIONS: LRG represents a novel serum biomarker for monitoring disease activity during therapy in autoimmune patients, particularly useful in patients with active disease but normal CRP levels.
20077577 'Your whole life, your whole world, it changes': partners' experiences of living with rheu 2010 Mar OBJECTIVES: Research suggests that rheumatoid arthritis (RA) can have a negative psychosocial impact on partners, as well as patients. However, until now there has been very little in-depth qualitative research in this area. The aim of this study was to explore the experiences of partners of people with RA. METHODS: Semi-structured interviews were conducted with a heterogeneous sample of eight partners of people with RA (six men, two women, age range 48-73 years). Transcripts were analysed thematically. RESULTS: Five overarching themes emerged: psychological burden in partners was substantial, as they experienced frustration and distress at watching their partner suffer and tried to protect their spouse from emotional and physical distress. 'It's a restricted life': partners reported having to cut back on previously enjoyable shared activities and had difficulty making future plans. Adjusting lives: partners had to make considerable adjustments to many aspects of their lives, and had adopted practical and psychological ways to cope. 'It's a joint approach': many partners discussed adopting a joint approach to managing the RA. Met and unmet support needs varied considerably, and many partners felt that a joint approach to treatment taken by health professionals is needed, which involves and recognizes their role. CONCLUSIONS: Partners of people with RA are vital to the patients' disease management, but the data show that many carry a substantial psychosocial burden. Healthcare professionals should be aware of this, so that couples coping with RA can be better supported.
20713883 Nonsteroidal anti-inflammatory drugs increase TNF production in rheumatoid synovial membra 2010 Sep 15 Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase activity and hence PG production. However, the ability of NSAIDs to ameliorate pain and tenderness does not prevent disease progression in rheumatoid arthritis, a disease whose pathogenesis is linked to the presence of proinflammatory cytokines, such as TNF-alpha. To understand this observation, we have examined the effect of NSAIDs on the production of clinically validated proinflammatory cytokines. We show that a variety of NSAIDs superinduce production of TNF from human peripheral blood monocytes and rheumatoid synovial membrane cultures. A randomized, double-blinded, crossover, placebo-controlled trial in healthy human volunteers also revealed that the NSAID drug celecoxib increased LPS-induced TNF production in whole blood. NSAID-mediated increases in TNF are reversed by either the addition of exogenous PGE(2) or by a PGE(2) EP2 receptor agonist, revealing that PGE(2) signaling via its EP2 receptor provides a valuable mechanism for controlling excess TNF production. Thus, by reducing the level of PGE(2), NSAIDs can increase TNF production and may exacerbate the proinflammatory environment both within the rheumatoid arthritis joint and the systemic environment.
19714343 [Bone densitometry in inflammatory rheumatic diseases : Characteristics of the measurement 2009 Dec Bone densitometry should be performed earlier in patients with inflammatory arthritis, since factors such as inflammation and drug therapy, in particular treatment with glucocorticoids, have an important impact on the development of osteoporosis. DXA (Dual energy X-ray Absorptiometry) is considered the gold standard for bone densitometry. According to the German guidelines for osteoporosis, bone densitometry plays a crucial role in the choice of therapy.In patients with rheumatoid arthritis, measurement of peripheral bone (forearm) density in addition to lumbar spine and hip is recommended, since local bone loss is pathognomonic for this disease. DXA measurements of the hand enable the diagnosis of juxtaarticular osteoporosis at an earlier stage; however, this has not yet been established in routine practise.Bone measurement in patients with ankylosing spondylitis can be performed in the lumbar spine and the hip at disease onset. In systemic lupus erythematosus, bone loss is more frequent in patients with high inflammatory activity. Patients with psoriasis arthritis frequently have osteoporosis in the case of a destructive development of the joints.
19817282 [Treatment of valgus deformity by total knee arthroplasty with modified Ranawat soft tissu 2009 Sep OBJECTIVE: To evaluate the efficacy of modified Ranawat soft tissue balance technique on total knee arthroplasty (TKA). METHODS: From January 2004 to June 2008, 34 cases (44 knees) of valgus deformity were treated with TKA. There were 5 males (5 knees) and 29 females (39 knees), aged 55-79 years old (average 60.3 years old) and including 18 left knees and 26 right knees. The deformity was caused by osteoarthritis in 9 cases, by rheumatoid arthritis in 19 cases, and by traumatic arthritis in 6 cases. According to Ranawat classification, there were 5 cases (5 knees) of type I and 29 cases (39 knees) of type II. All patients were performed modified Ranawat soft tissue balance technology. RESULTS: The operative time was (65 +/- 7) minutes. Burst fracture of femoral condyle occurred and internal fixation was selected in 1 case of rheumatoid arthritis. Small incision necrosis occurred and healed after debridement in 1 case of rheumatoid arthritis. Incision healed by first intention in other cases. Adhesions occurred in 1 case (1 knee) and hydrarthrosis in 4 cases (4 knees), all cured after symptomatic treatment. All patients were followed up 6 months to 5 years with an average of 2.6 years. All patients had no complications of deep vein thrombosis, dislocation, vascular injury and nerve injury. X-ray films showed no signs of prosthesis loosening and infection at 1 year after operation. The X-ray films showed statistically significant differences (P < 0.05) in anatomic valgus angulation between preoperation and 1 week after operation [(25.4 +/- 3.1) degrees vs (3.8 +/- 1.2) degrees]. There were statistically significant differences in modified KSS score between preoperation and 1, 2 years postoperatively (P < 0.05). CONCLUSION: It is a simple and effective way to treat the valgus deformity with modified Ranawat soft tissue balance technique in TKA, which can achieve the satisfactory results in the knee stability, the range of motion and the deformity correction.
20007589 ERK-dependent T cell receptor threshold calibration in rheumatoid arthritis. 2009 Dec 15 Immune responses to citrullinated neoantigens and clinical efficacy of costimulation blockade indicate a general defect in maintaining T cell tolerance in rheumatoid arthritis (RA). To examine whether TCR threshold calibration contributes to disease pathogenesis, signaling in RA T cells was quantified. RA patients had a selective increase in ERK phosphorylation compared with demographically matched controls due to a mechanism distal of Ras activation. Increased ERK responses included naive and memory CD4 and CD8 T cells and did not correlate with disease activity. The augmented ERK activity delayed SHP-1 recruitment to the TCR synapse and sustained TCR-induced Zap70 and NF-kappaB signaling, facilitating responses to suboptimal stimulation. Increased responsiveness of the ERK pathway was also a characteristic finding in the SKG mouse model of RA where it preceded clinical symptoms. Treatment with subtherapeutic doses of a MEK-1/2 inhibitor delayed arthritis onset and reduced severity, suggesting that increased ERK phosphorylation predisposes for autoimmunity and can be targeted to prevent disease.
20547658 Physical function improvements and relief from fatigue and pain are associated with increa 2010 Oct OBJECTIVES: To evaluate the association between improvements in physical function, fatigue and pain and improvements in productivity at work and at home in patients treated with certolizumab pegol (CZP) in combination with MTX. METHODS: Physical function, fatigue and pain were assessed in two CZP clinical trials (Rheumatoid Arthritis PreventIon of structural Damage 1 and 2) using the HAQ-Disability Index (HAQ-DI), Fatigue Assessment Scale (FAS) and Patient Assessment of Pain, with minimal clinically important differences (MCIDs) defined as ≥ 0.22, ≥ 1 and ≥ 10 points, respectively. Work and home productivity were evaluated using the RA-specific Work Productivity Survey (WPS-RA). The odds of achieving an HAQ-DI, FAS or pain 'response' at Week 12, defined as improvements ≥ MCID, were compared between CZP and control groups. Improvements in productivity at Week 12 were compared between CZP-treated HAQ-DI, FAS or pain responders and non-responders. RESULTS: The odds of achieving improvements ≥ MCID were five times higher for pain, and two to three times higher for physical function and fatigue, in patients receiving CZP vs control. Per month, responders reported significantly greater improvements in productivity at work and reduced interference of RA with their work productivity than non-responders. Responders also reported significantly greater improvements in productivity at home and participation in family, social and leisure activities. CONCLUSIONS: This study demonstrated a clear association between patient-reported improvements in physical function, fatigue and pain, and improvements in productivity both at work and home.
19405833 Cytokine gene polymorphisms associated with rheumatoid arthritis and periodontitis in Japa 2009 May BACKGROUND: Cytokines play a major role in the pathogenesis of rheumatoid arthritis (RA) and periodontitis. Both diseases were previously shown to be partly influenced by cytokine gene polymorphisms. Therefore, we evaluated whether the distributions of the cytokine genotypes were unique to subjects with both diseases. METHODS: The study subjects consisted of Japanese adults with RA (RA group; n = 153), periodontitis only (P group; n = 117), and healthy individuals (H group; n = 108). Clinical periodontal condition was defined by measurements of probing depth, clinical attachment level, and bleeding on probing. Genomic DNA was isolated from peripheral blood and analyzed for the determination of 16 gene polymorphisms encoding interleukin (IL)-1, -2, -4, -6, and -10, tumor necrosis factor-alpha, and transforming growth factor-beta 1. RESULTS: The frequency of patients with RA who exhibited periodontitis was 89.5% (RA + P group; n = 137). No significant differences were observed in any of the frequencies of cytokine genotypes and alleles among the subject groups. After adjustment for age, gender, and smoking status, multiple logistic regression analysis revealed a significant difference in the distribution of IL-1B +3954 genotypes between RA + P and P groups (P = 0.006) and between RA + P and H groups (P = 0.008). CONCLUSION: Japanese individuals with RA and periodontitis may exhibit different distributions of IL-1B +3954 genotypes than healthy controls and subjects with periodontitis only.
19467351 Nitrated type III collagen as a biological marker of nitric oxide-mediated synovial tissue 2009 Oct OBJECTIVES: Nitric oxide (NO) is a major mediator of joint tissue inflammation and damage in osteoarthritis (OA) and mediates the nitration of tyrosine (Y*) residues in proteins. We investigated the nitration of type III collagen, a major constituent of synovial membrane, in knee OA. METHODS: A polyclonal antibody directed against the nitrated QY*DSY*DVKSG sequence from type III collagen N-telopeptide was generated. Synovial tissues from patients with knee OA (n=4) and rheumatoid arthritis (RA, n=4) were analyzed by immunohistochemistry for IIINys. Serum IIINys levels were measured by enzyme-linked immunosorbent assay in 87 patients with painful knee OA (mean age: 63.0+/-8.0 years, Kellgren-Lawrence score II-III) and in 40 sex and age-matched healthy controls. RESULTS: Competition experiments using various nitrated and un-nitrated type III collagen and derived sequences, showed that the antibody was highly specific for the nitrated IIINys sequence. High IIINys immunoreactivity was detected in the synovial tissues from all patients with OA and RA with a preferential localization in the intimal layer. Serum IIINys levels were on average 1.5-fold higher (P<0.0001) in patients with knee OA than in healthy controls and significantly correlated with C-reactive protein values (r=0.40, P<0.005). CONCLUSIONS: Nitration of tyrosine residues of type III collagen N-telopeptide is increased in the synovial tissue of patients with knee OA. Measurements of serum IIINys level may be useful for the clinical investigation of oxidative-related alterations of synovial tissue metabolism in OA.
21618398 The recognition and assessment of cardiovascular risk in people with rheumatoid arthritis 2011 Jun OBJECTIVES: To investigate how well recognized the association between rheumatoid arthritis (RA) and excess cardiovascular (CV) risk is within primary care and the current assessment strategies being employed by general practitioners (GPs). METHODS: Questionnaires were sent to all 376 GPs in the Worcestershire Primary Care Trust. RESULTS: Thirty-two per cent of GPs identified RA as an independent risk factor for CV disease. Fifteen per cent and 34%, respectively, assessed their RA patients for primary and secondary prevention of their CV risks. Of those GPs who made an assessment, 18.4% adjusted the calculated risk derived from standard charts. The frequency of assessment was greater among GPs who had received a form of education about the association between CV disease and RA. However, of the GPs identifying this susceptibility, only 40% performed any form of primary prevention risk assessment. CONCLUSIONS: At present, the excess risk of CV disease conferred by RA is under-recognized and under-assessed in primary care. Currently, educational resources on this topic targeted at GPs are lacking and may in part account for our findings. However, even when GPs did identify the risk of CV disease in RA or had received education about it, this did not consistently change their clinical management. Further work to promote knowledge and management strategies for CV disease in RA is therefore needed to improve the care of patients with this condition.
20665136 Measurement of erythrocyte methotrexate polyglutamate levels: ready for clinical use in rh 2010 Oct Methotrexate (MTX) is one of the most commonly prescribed and most effective drugs for the treatment of rheumatoid arthritis (RA). Given the partial response of many patients and the side effect profile of the drug, there is considerable interest in identifying biomarkers to guide MTX therapy in RA. Upon entering cells, MTX is polyglutamated. Measuring MTX polyglutamate (MTX PG) levels in circulating red blood cells has been proposed as an objective measure to help optimize MTX therapy in RA. Data are conflicting with regard to the clinical utility of MTX PG measurements as a predictor of the efficacy or toxicity of low-dose MTX effects in RA. Should large, randomized clinical trials of this assay show consistent, reproducible, long-term correlations between MTX PG levels and efficacy or toxicity, this test could become a prominent tool for clinicians to optimize the use of MTX in treating RA.
20201080 Autocitrullination of human peptidyl arginine deiminase type 4 regulates protein citrullin 2010 Jun OBJECTIVE: To address mechanisms that control the activity of human peptidyl arginine deiminase type 4 (PAD-4). METHODS: PAD-4 autocitrullination was determined by anti-modified citrulline immunoblotting, using purified recombinant and endogenous PAD-4 from activated human primary neutrophils and cell lines expressing PAD-4. The citrullination sites in PAD-4 were determined by mass spectrometry. Mechanisms of autocitrullination-induced inactivation and the functional consequences of autocitrullination in PAD-4 polymorphic variants were addressed using purified components and cell lines expressing PAD-4 wild-type, PAD-4 mutant, and PAD-4 polymorphic variants relevant to rheumatoid arthritis (RA). RESULTS: PAD-4 is autocitrullinated in vitro and during activation of primary cells and cell lines expressing PAD-4. Interestingly, this modification inactivated the function of the enzyme. The efficiency of inactivation differed among genetically defined PAD-4 variants relevant to RA. PAD-4 was citrullinated at 10 sites, which are clustered into 3 distinct regions, including a cluster of arginines around the active site cleft where Arg-372 and -374 were identified as the potential autocitrullination targets that inactivate the enzyme. Autocitrullination also modified the structure of PAD-4, abrogating its recognition by multiple rabbit antibodies, but augmenting its recognition by human anti-PAD-4 autoantibodies. CONCLUSION: Our findings suggest that autocitrullination regulates the production of citrullinated proteins during cell activation, and that this is affected by structural polymorphisms in PAD-4. Autocitrullination also influences PAD-4 structure and immune response.
19995747 Heart disease and rheumatoid arthritis: understanding the risks. 2010 Jan Patients with rheumatoid arthritis (RA) are at increased risk of mortality compared with the general population. Evidence suggests that this increased mortality can largely be attributed to increased cardiovascular death. In a retrospective study of an inception cohort of RA patients in Rochester, MN, the contribution of traditional and RA-specific risk factors was investigated to this increased risk of cardiovascular morbidity and mortality. Several traditional cardiovascular risk factors were found to behave differently in RA patients. In addition, their associations with cardiovascular disease are weaker in RA patients as increased inflammation associated with RA also appears to contribute substantially to the increased cardiovascular mortality. Furthermore, the impact of disease-modifying antirheumatic drugs and biologicals on cardiovascular disease in RA patients is unclear. Cardiovascular risk scores for the general population may underestimate the risk for RA patients. Together with other studies that have demonstrated similar associations between RA and cardiovascular mortality, these data suggest that optimal control of cardiovascular risk factors is important, but not sufficient in RA patients. RA-specific cardiovascular risk prediction tools are needed, as well as clinical trials to assess the impact of therapies and tight control of inflammation in RA patients on cardiovascular outcomes and mortality.
20104905 Quantitation of saccharide compositions of O-glycans by mass spectrometry of glycopeptides 2010 Mar 5 Profiling of oligosaccharide structures is widely utilized for both identification and evaluation of glycobiomarkers, and site-specific profiling of N-linked glycans of glycoproteins is conducted by mass spectrometry of glycopeptides. However, our knowledge of mucin-type O-glycans including site occupancy and profile variance, as well as attachment sites, is quite limited. Saccharide compositions and site-occupancy of O-glycans were calculated from the signal intensity of glycopeptide ions in the mass spectra and tandem mass spectra from electron transfer dissociation. The results for two major plasma glycoproteins, IgA1 and hemopexin, representing clustered and scattered O-glycan attachments, respectively, indicated that the variability in modifications among individuals is so small as to justify rigorous standards enabling reliable detection of disease-related alterations. Indeed, this method revealed a novel abnormality associated with rheumatoid arthritis: a significant decrease in the N-acetylgalactosamine content of IgA1 O-glycans, indicating that the glycosylation abnormality is not limited to hypogalactosylation of IgG N-glycans in chronic inflammatory conditions.
20172056 Immunosenescence and juvenile idiopathic arthritis. 2012 Mar Aging of the immune system (immunosenescence) is characterized by diminished thymus function, decreased output of recent thymic emigrants, compensatory peripheral proliferation of mature T cells and oligoclonal expansions of specific CD28(-) T cells. Clinical consequences are poor responses to new antigens or vaccinations, increased infection rates with higher morbidity and mortality, and increasing incidence of autoimmune diseases with advancing age. Premature immunosenescence is suggested to play a role in the pathogenesis of adult rheumatoid arthritis and in children with juvenile idiopathic arthritis (JIA). However, so far, there is not enough evidence for supporting one of the two theories: the first, favoring premature immunosenscence in children developing autoimmune conditions as the primary defect causing break-down of self-tolerance; the second, that premature immunosenescence in children with autoimmune disorders is secondary to chronic stimulation and activation of the immune system by inflammatory processes by the autoimmune disease itself. This contradictory view of etiology and pathogenesis of autoimmune diseases in the very young underlines the need for population-based longitudinal studies on immune-risk factors for autoimmune diseases beginning at infancy.
19664198 Is there a feudal hierarchy amongst regulatory immune cells? More than just Tregs. 2009 Nature has provided the developing immune system with several checkpoints important for the maintenance of tolerance and the prevention of autoimmunity. The regulatory mechanisms operating in the periphery of the system are mediated by subsets of regulatory cells, now considered principal contributors to peripheral tolerance. Regulatory T cells (Tregs) have received titanic interest in the past decade, placing them at the centre of immuno-suppressive reactions. However, it has become clearer that other immune suppressive cells inhibit auto-reactivity as effectively as Tregs. The function of Tregs and other regulatory cells in rheumatoid arthritis will be discussed in this review.
19201028 Synergism between tumor necrosis factor alpha and interleukin-17 to induce IL-23 p19 expre 2009 May In order to determine the mechanisms by which a chronic inflammatory network can be maintained in the arthritic joint, we examined whether fibroblast-like synoviocytes (FLS) could provide feedback signals after their stimulation by inflammatory cytokines. FLS and dermal fibroblasts (DF) were derived from rheumatoid arthritis (RA), osteoarthritis (OA) and post-trauma patients. These two cell types were then stimulated with 10 nanogram/ml of TNFalpha, IL-1beta and IL-17 alone or in combination treatments. Specific mRNA expression of IL-23 p19 was quantitated by real-time PCR and its protein by immunoprecipitation. A striking specific synergistic induction of IL-23 p19 versus IL-12 p35 mRNA expression was noted after stimulation with IL-17 and TNFalpha in FLS, and to a lesser degree in DF (p<0.043). This synergistic response was composed of an initial priming step by IL-17, thus making FLS hyperresponsive to TNFalpha-mediated stimulation. In contrast, IL-1beta mediated induction of IL-23 p19 expression was cell-specific. Induction of IL-23 p19 expression by IL-1beta was present in FLS but almost absent in the DF derived from the same patients. Furthermore, IL-1beta did not synergize with IL-17 to induce IL-23 p19 expression. Immunoprecipitation of FLS cellular lysates after stimulation with IL-17 and TNFalpha detected p19 protein and this was enhanced by the addition of IL-1beta. However, no co-immunoprecipitation of the p40 subunit of IL-23 was noted from the same cells. Thus, FLS are potently regulated by inflammatory cytokines to specifically express IL-23 p19. Additional byproducts of the inflammatory milieu may be required for the generation and secretion of bioactive IL-23.
20200272 Mast cells express IL-17A in rheumatoid arthritis synovium. 2010 Apr 1 The proinflammatory cytokine IL-17A is considered a crucial player in rheumatoid arthritis (RA) pathogenesis. In experimental models of autoimmune arthritis, it has been suggested that the cellular source of IL-17A is CD4(+) T cells (Th17 cells). However, little is known about the source of IL-17 in human inflamed RA tissue. We explored the cellular sources of IL-17A in human RA synovium. Surprisingly, only a small proportion of IL-17-expressing cells were T cells, and these were CCR6 negative. Unexpectedly, the majority of IL-17A expression colocalized within mast cells. Furthermore, we demonstrated in vitro that mast cells produced RORC-dependent IL-17A upon stimulation with TNF-alpha, IgG complexes, C5a, and LPS. These data are consistent with a crucial role for IL-17A in RA pathogenesis but suggest that in addition to T cells innate immune pathways particularly mediated via mast cells may be an important component of the effector IL-17A response.
20610444 Investigation into the impact of abatacept on sleep quality in patients with rheumatoid ar 2010 Oct OBJECTIVES: To assess the impact of abatacept on sleep quality in patients with rheumatoid arthritis (RA), and the validity of the sleep disturbance scale of the Medical Outcomes Study Sleep Questionnaire (MOS-Sleep). METHODS: Data from two randomised, double-blind, placebo-controlled abatacept trials (Abatacept Trial in Treatment of Antitumor necrosis factor IN adequate responders (ATTAIN) and Abatacept in Inadequate responders to Methotrexate (AIM)) were analysed. Sleep quality was assessed using the MOS-Sleep. Changes in the Sleep Disturbance Scale were assessed according to clinical responses (including American College of Rheumatology (ACR) and Disease Activity Score 28 C-reactive protein criteria). Correlations between sleep disturbance and patient-reported outcomes were assessed. The sensitivity to change of sleep disturbance was assessed by calculating the standardised response means (SRMs). RESULTS: 258 abatacept- and 133 placebo-treated patients in ATTAIN and 433 abatacept- and 219 placebo-treated patients in AIM were analysed. In ATTAIN, mean improvements to month 6 were significantly greater for patients treated with abatacept than for placebo patients in sleep disturbance (11.3 vs 2.9, p<0.001), sleep adequacy (9.0 vs 0.6, p<0.05), somnolence (10.5 vs 1.6, p<0.001) and Sleep Problems Index (SPI) I (9.5 vs 1.4, p<0.0001) and II (9.8 vs 2.1, p<0.001); mean improvements in AIM to year 1 were statistically significant for sleep disturbance (12.9 vs 8.9, p<0.05) and SPI I (9.4 vs 6.7, p<0.05) and II (10.4 vs 7.3, p<0.05). Associations between mean improvements in sleep disturbance and clinical responses were statistically significant (3.8, 12.7, 18.0, p<0.001 and 5.0, 11.5, 15.7, p<0.001 for European League Against Rheumatism responses, none, moderate and good in ATTAIN and AIM, respectively; 10.2, 14.4, 22.8, p=0.007 and 10.9, 14.9, 17.7, p=0.006 for ACR 20, 50 and 70 responses in ATTAIN and AIM, respectively). SRMs for sleep disturbance were 0.38 (ATTAIN) and 0.19 (AIM). CONCLUSIONS: Abatacept treatment provides significant improvements in multiple aspects of sleep in patients with RA. The Sleep Disturbance Scale of the MOS-Sleep shows validity, reliability and sensitivity to change.