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ID PMID Title PublicationDate abstract
22491018 Genome-wide association analysis implicates the involvement of eight loci with response to 2013 Jun Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease affecting the joints. A heterogeneous response to available therapies demonstrates the need to identify those patients likely to benefit from a particular therapy. Our objective was to identify genetic factors associated with response to tocilizumab, a humanized monoclonal antibody targeting the interleukin (IL)-6 receptor, recently approved for treating RA. We report the first genome-wide association study on the response to tocilizumab in 1683 subjects with RA from six clinical studies. Putative associations were identified with eight loci, previously unrecognized as linked to the IL-6 pathway or associated with RA risk. This study suggests that it is unlikely that a major genetic determinant of response exists, and it illustrates the complexity of performing genome-wide association scans in clinical trials.
22457007 Baseline anti-citrullinated peptide antibody (ACPA) titers and serum interleukin-6 (IL-6) 2013 Feb A prospective study was made to seek for a convenient biomarker to predict progression of bone destruction (PBD) in early stages of rheumatoid arthritis (ERA). All participated patients had definite RA and their radiographic stages were mild less than stage II of the Steinbrocker classification, naïve for treatment of any DMARDs or corticosteroids. After the entry, they were treated according to the 2002 ACR management guideline for RA. The candidate biomarkers (RF-IgM, RF-IgG, CARF, ACPA, CRP, ESR, NTx, MMP-3, IL-6 and osteopontin) were measured at the entry. PBD was assessed radiographically by interval changes in the modified Sharp scores (ΔSHS) for 24 months. The associations between ΔSHS and baseline biomarkers were assessed statistically by multivariate regression analyses. Both the baseline ACPA and IL-6 levels correlated with PBD, suggesting that they could predict PBD in ERA.
23434196 Pentraxin 3, a novel cardiovascular biomarker, is expressed in aortic specimens of patient 2013 Sep BACKGROUND: The aims were to evaluate the presence and extent of pentraxin 3 depositions in specimens from the outer layers of the aorta and from the internal thoracic artery of patients with coronary artery disease with and without rheumatoid arthritis and to search for relationships between pentraxin 3 and vascular inflammation. METHODS: Using histochemistry and immunohistochemistry, we examined biopsies from the aortic adventitia and from the internal thoracic artery (both with adjacent perivascular tissue), removed during coronary artery bypass grafting in 19 rheumatoid arthritis and 20 non-rheumatoid-arthritis patients, for presence/extent of pentraxin 3 depositions, inflammatory cell infiltrates, and fibrosis. RESULTS: In the aorta, pentraxin 3 deposition occurred in all specimens, mostly at sites with inflammatory cell infiltrates or fibrosis, and their extent was related to the extent of inflammatory cell infiltrates (rho=0.43, 95% confidence interval: 0.13-0.66, P=.007). The extent of pentraxin 3 and inflammatory cell infiltrates in the aorta was similar in rheumatoid arthritis and non-rheumatoid-arthritis patients, but rheumatoid arthritis patients had more fibrosis and a lower proportion of T-cells in inflammatory cell infiltrates. In the internal thoracic artery, pentraxin 3 occurred only in 36% patients, and inflammatory cell infiltrates and fibrosis occurred in none. CONCLUSIONS: Pentraxin 3 depositions in the outer aortic layers are common and are related to the local inflammation. On the other hand, they occur less frequently in the internal thoracic artery, i.e., a vessel highly resistant to atherosclerosis. Rheumatoid arthritis patients had more pronounced fibrosis in the aortic specimens and a different leukocytic response than non-rheumatoid-arthritis patients. In theory, pentraxin 3 might modulate the inflammatory process involved in the pathogenesis of cardiovascular disease and represent a target for new therapies.
24521636 Interleukin-4 in rheumatoid arthritis patients with interstitial lung disease: a pilot stu 2013 Dec BACKGROUND & OBJECTIVES: Interstitial lung disease (ILD) is a progressive complication in patients with rheumatoid arthritis (RA). Although the precise mechanisms of ILD are not fully understood, Th2 cytokines, especially interleukin (IL)-4 may play an important role in the processes of fibrosis. We, therefore, investigated the role of Th2 cytokines, including IL-4, IL-13 and IL-5 in RA patients with or without ILD. METHODS: Serum samples were obtained from 63 patients with RA. Among them, 29 RA patients had ILD while the remaining 34 patients were without ILD. The bronchoalveolar lavage fluids (BALF) from 11 RA patients with ILD and eight patients without ILD were also collected. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the levels of IL-4, IL-13 and IL-5 both in serum and in BALF. RESULTS: The levels of IL-4 were increased in the serum and BALF of RA patients with ILD compared with RA patients without ILD. There were no differences in the levels of IL-13 and IL-5 among the different groups. INTERPRETATION & CONCLUSION: The present results indicate that IL-4 seems to play an important role in the development of ILD in patients with RA.
24800519 [Comparative study of the influence of melatonin and diclofenac on some hematologic indice 2014 Pineal hormone melatonin (1 and 5 mg/kg) and diclofenac (8 mg/kg) significantly limited hematologic indices of inflammation and immunologic reactivity in rats with experimental adjuvant arthritis. The effect of melatonin was more pronounced than that of diclofenac.
22623288 Body mass index and the rheumatoid arthritis swollen joint count: an observational study. 2013 Jan OBJECTIVE: Obesity is a prevalent condition and a serious health concern. The relationship between obesity and rheumatoid arthritis (RA) disease activity and severity has not been adequately examined, and there are concerns that periarticular adipose tissue may reduce the utility of the joint examination. METHODS: We used a cross-sectional study to compare the performance of swollen joint count (SJC) in subjects with RA across body mass index (BMI) strata. Specifically, regression techniques tested for associations of SJC and 7 RA disease activity/severity measures (including high-sensitivity C-reactive protein level, radiographic changes, and Multidimensional Health Assessment Questionnaire scores) within BMI quartiles. We also evaluated the association of BMI with radiographic evidence of RA in multivariate analyses and the association of BMI with SJC. Clinical and laboratory data from 980 Veterans Affairs Rheumatoid Arthritis registry participants were analyzed using linear and logistic regression. RESULTS: Associations were evident between SJC and 6 of the 7 examined RA disease activity/severity measures. SJC predicts RA disease activity/severity in more obese subjects at least as well as in subjects with lower BMIs, and there was a trend toward better performance in individuals with higher BMIs. Subjects with higher BMIs were marginally less likely to be characterized by radiographic changes (odds ratio 0.98, P = 0.051). We found no association between BMI and SJC. CONCLUSION: BMI does not obscure the relationship of SJC and objective disease activity measures. There is a borderline association of higher BMI and the likelihood of radiographic changes characteristic of RA after controlling for clinical characteristics.
24333265 Improving cardiovascular outcomes in rheumatic diseases: therapeutic potential of circulat 2014 May Patients with Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) have a significantly increased risk of cardiovascular disease (CVD). The reason for this is unclear but may be due, at least in part, to the failure of endothelial repair mechanisms. Over the last 15 years there has been much interest in the mechanisms of endothelial renewal and its potential as a therapy for CVD. In the circulation there are two distinct populations of cells; myeloid angiogenic cells (MACs) which augment repair by the paracrine secretion of angiogenic factors, and outgrowth endothelial cells (OECs) which are true endothelial progenitor cells (EPCs) and promote vasculogenesis by differentiating into mature endothelium. There are marked abnormalities in the number and function of these cells in patients with RA and SLE. Inflammatory cytokines including interferon-alpha (IFNα) and tumour-necrosis factor alpha (TNFα) both impair MAC and OEC function ex vivo and may therefore contribute to the CVD risk in these patients. Whilst administration of mononuclear cells, MACs and other progenitors has improved cardiovascular outcomes in the acute setting, this is not a viable option in chronic disease. The pharmacological manipulation of MAC/OEC function in vivo however has the potential to significantly improve endothelial repair and thus reduce CVD in this high risk population.
25065918 Construct validity, reliability, response rate, and association with disease activity of t 2015 Mar OBJECTIVE: First objective is to validate the Disabilities of the Arm, Shoulder and Hand (DASH) and Quick DASH (QuickDASH) questionnaire in rheumatoid arthritis (RA) patients with functional upper extremity impairment. Next is to clarify which clinical factor is associating with QuickDASH using a large cohort of RA. METHODS: The QuickDASH and DASH were applied to our 94 RA patients who underwent surgery for functional upper extremity impairment. Next, the QuickDASH was applied to our cohort of 5191 Japanese patients with RA. RESULTS: In the first cohort of 94 RA patients, both QuickDASH and DASH displayed excellent reliability and validity. The response rate of patients < 65 and ≥ 65 years of age showed significant difference in the DASH but not in the QuickDASH. In the second cohort with 5191 RA patients, QuickDASH showed a high response rate (93%) and good to moderate correlation with Japanese version of the Health Assessment Questionnaire (r = 0.88) and disease activity score of 28 (DAS28, r = 0.53). Change in QuickDASH score and DAS28-based European League Against Rheumatism response showed significant correlation. CONCLUSION: QuickDASH seems suitable for evaluating upper extremity impairment, disability index, and disease control in a large cohort of RA patients including elderly patients.
22586162 Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arth 2013 Mar INTRODUCTION: Interleukin-6 receptor (IL-6R) blockade improves the signs and symptoms of rheumatoid arthritis (RA) and retards bone damage. Whether IL-6R blockade allows repair of existing bone erosions is so far unclear. METHODS: This study examined bone erosions in the metacarpophalangeal joints of 20 patients receiving treatment with the IL-6R blocker tocilizumab using micro CT (µCT). The maximal width and depth of individual bone erosions was measured at baseline and after 1 year of treatment. RESULTS: 133 bone erosions were identified at baseline with a mean (±SD) size of 2.23±1.26 mm and depth of 2.16±1.50 mm. Distribution analysis showed predominant involvement of the second compared with the third and fourth metacarpophalangeal joints, the metacarpal heads compared with the phalangeal bases and the radial quadrants compared with all other surfaces. Repair of bone erosions during tocilizumab treatment was confined to those lesions showing sclerosis at baseline and/or at follow-up and those with a width larger than 1.6 mm. The mean decrease in width of sclerosed erosions was thus 0.14±0.05 mm (p=0.0086) and 0.20±0.08 mm (p=0.019) for sclerosing lesions after 1 year of treatment. CONCLUSIONS: Blockade of IL-6R by tocilizumab can induce limited repair in a subset of erosions, particularly in large lesions with sclerosis. Repair of erosions during tocilizumab treatment reflects the favourable impact of IL-6R blockade on local bone remodelling in patients with RA.
25182675 Health economic modelling of treatment sequences for rheumatoid arthritis: a systematic re 2014 Oct The objective of the work reported in this paper was to critically assess how sequential disease-modifying anti-rheumatic drugs (DMARDs) have been modelled in the context of economic evaluation of the use of DMARDs for treatment of rheumatoid arthritis (RA). A secondary purpose was to identify the methodological challenges of modelling sequential therapies. Systematic searches of 10 databases were undertaken in February 2013. Studies were included if they were in the English language and a full comparative economic evaluation was reported. They were appraised by use of the Drummond checklist (Appendix to this paper). Data extracted included economic evaluation data, data relating to sequential treatment, and data on the modelling methods used. Fifty-seven studies were identified, with 25 (44 %) modelling a sequence of treatments. Forty-three (75 %) were cost-utility analyses. Eleven (19 %) were UK studies and 11 (19 %) were US. The remainder were mainly European (26 (46 %)). A distinction was made between studies of recent-onset RA (14 (25 %)) and those of established RA (42 (74 %)). One study (1 %) was unclear. Individual-level models were more likely to meet the Drummond criteria and evaluate sequences. No study identified an optimum sequence of multiple treatments given a set of treatment options. The level of reporting of the methods and evidence used to assess the effect of downstream treatments in the sequence was generally poor. When lifelong models and downstream treatment sequences were considered, evidence gaps were identified. The review discovered that methods have not been consistently applied, leading to varied estimates of cost-effectiveness. Treatment sequences have not been fully considered and modelled, potentially resulting in inaccurate estimates of cost-effectiveness.
24113730 Ultrasound assessment for the rapid classification of early arthritis patients. 2013 Dec OBJECTIVE: The present study aimed to assess the role of ultrasound (US) in the rapid classification of early rheumatoid arthritis (RA) by investigating whether the US features of inflammation and bone damage in early arthritis overlap with the actual clinical concept of classifying and identifying an aggressive disease. METHODS: Patients with recent-onset arthritis of at least 1 peripheral joint of the hands and/or the feet were consecutively included in this study. Clinical examination, laboratory tests, the Disease Activity Score 28 (DAS28), and the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA were assessed for all patients. Medication with disease-modifying antirheumatic drugs was recorded. Ultrasound assessment was performed at the following anatomical sites: wrists, metacarpophalangeal joints 2 to 5, and metatarsophalangeal joints 2 to 5 for assessing the presence/absence of synovial hypertrophy, the presence/absence of power Doppler signal, and the presence/absence of bone erosions.The US features of inflammation and bone damage were analyzed in comparison with the DAS28, with the presence/absence of rheumatoid factor and anti-cyclic citrullinated peptide, with the fulfillment of the new 2010 ACR/EULAR classification criteria, and with the initiated disease-modifying antirheumatic drug. The prescription of methotrexate was considered a marker of an aggressive disease. RESULTS: The US features of inflammation and bone damage correlated with the activity scores measured by the DAS28. The presence of US bone erosions overlapped with the presence of rheumatoid factor and anti-cyclic citrullinated antibodies. Synovial hypertrophy, intra-articular power Doppler signal, and bone erosions detected in at least 1 anatomical site were seen in patients fulfilling (77.7%) and in patients not fulfilling (72.7%) the 2010 ACR/EULAR classification criteria for RA. Synovial hypertrophy was found in at least 1 site in 83.3% and 58.8% of patients in whom methotrexate was prescribed and in whom methotrexate was not prescribed, respectively (P = 0.01). The US features were not correlated with the initiation of sulfasalazine or hydroxychloroquine. The patients presenting bone erosions received in significantly higher percentages the indication for methotrexate (50%) compared with sulfasalazine (20%), P = 0.03, or hydroxychloroquine (26%), P = 0.05. CONCLUSIONS: The US features of inflammation might be of help in classifying early arthritis patients despite the presence of the immune markers for RA. Together with the US features of bone damage, these might be used as an indicator of a more aggressive disease. The absence of correlation between the US findings of RA and the 2010 ACR/EULAR classification criteria indicates a possible independent contribution of US in the understanding of the future evolution of these patients.
24595319 Preclinical impairment of myocardial function in rheumatoid arthritis patients. Detection 2015 Jun OBJECTIVES: The incidence of heart failure is higher in patients with rheumatoid arthritis (RA) than in the general population and contributes to elevated cardiovascular mortality and morbidity rates. Impaired myocardial function can be detected by a novel echocardiographic method, speckle tracking echocardiography (STE), when conventional methods have yielded normal findings. The aim of our study was to investigate the effect of disease duration on myocardial strain and strain rate parameters in patients with RA. METHODS: This cross-sectional study included 37 RA patients [n=16, female gender n=16, mean age, 45.7 ± 9 years in the early-stage disease (ESD); n= 21, female gender n=19, 45.7 ± 16.8 years in the advanced-stage disease (ASD) group] who were compared according to early disease duration and advanced-stage disease (2.8 ± 1.2 vs. 14.6 ± 6.8 years, respectively). Hypertension, diabetes mellitus, and other cardiovascular risk factors were excluded. Offline analysis of STE was performed and data between the two groups were compared. RESULTS: RS, RSR-E, and RSR-E/A values were statistically significantly lower in patients with ASD. Circumferential strain and strain rate were similar between the two groups. Except for LSR-E/A values, LS, LSR-S, LSR-E, and LSR-A values were decreased in patients with ASD. CONCLUSION: RA patients without clinical evidence of cardiovascular disease and in the absence of traditional cardiovascular risk factors can be followed up with STE. In this way, early impairment of myocardial deformation can be detected before the appearance of any clinical evidence of cardiac involvement.
24320944 Social support as a moderator of functional disability's effect on depressive feelings in 2014 Feb OBJECTIVE: To examine associations of depressive feelings with disease-related variables and explore the moderating effect of social support on depressive feelings in individuals with early rheumatoid arthritis (RA) prospectively over 4 years. METHOD: Data were collected annually over 4 years. The sample consisted of 124 individuals with diagnosed RA (85.5% women; mean age 47.9 years; mean disease duration 22.2 months). The strength of cross-sectional and prospective associations of sociodemographic, disease-related variables and the direct and moderating effects of social support on depression were tested using correlations, multilevel models, and hierarchical linear regressions. RESULTS: The study showed that emotional support moderated the influence of functional disability on depressive feelings in individuals with RA. This was not detected for instrumental support. Further prospective associations between functional status, marital status, and depressive feelings were also found. Overall, the strongest association was found between initial depressive feelings and depressive feelings over time. CONCLUSIONS: Initial depression seemed to be a risk factor in explaining later depressive feelings, but emotional support might be prospectively beneficial, especially for individuals with higher levels of disability. Early detection of individuals at risk for depression and providing interventions aimed at the specific functions of social support might help to decrease mental health problems.
23431244 Metabolic syndrome in rheumatoid arthritis. 2013 Insulin resistance is an essential feature of the metabolic syndrome that has been linked to rheumatoid arthritis (RA). Understanding how inflammation arising in one tissue affects the physiology and pathology of other organs remains an unanswered question with therapeutic implications for chronic conditions including obesity, diabetes mellitus, atherosclerosis, and RA. Adipokines may play a role in the development of atherogenesis in patients with RA. Biologic therapies, such as TNF-α antagonists, that block proinflammatory cytokines have beneficial effects on the insulin resistance that is often observed in patients with RA.
24614279 Disease activity or remission of rheumatoid arthritis before, during and following pregnan 2014 May PURPOSE OF REVIEW: Disease activity of rheumatoid arthritis (RA) can ameliorate spontaneously during pregnancy; however, adequate measurement of disease activity during pregnancy is a challenge, as is quantifying disease improvement during pregnancy and disease flare postpartum. Adverse pregnancy outcomes may be related to high disease activity during pregnancy, the full extent of which remains to be fully defined. RECENT FINDINGS: Disease activity might best be measured during pregnancy with DAS28-CRP without visual analogue scale (VAS) general health. Pregnancy outcome seems to be worse in patients with RA compared with healthy controls. High disease activity of RA may contribute importantly both to the longer time to conceive and worse pregnancy outcome. SUMMARY: Low disease activity of RA before, during and after pregnancy may be best for both mother and child. Counselling of patients on reproductive health and preconception treat-to-target management may help to achieve lower disease activity. This may result in better pregnancy outcomes.
25253504 Adjusting for comorbidities in cost of illness studies. 2015 Jan MOTIVATION: Differences in cost of illness (COI) methodological approaches have led to disparate results. This analysis examines two sources of this variation: specification of comorbidities in the estimated cost models and assumed prevalence rates used for generating aggregate costs. The study provides guidance in determining which comorbidities are important to include and how to handle uncertainty in optimal model specification and prevalence rate assumptions. METHODS: Comorbidities are categorized into four types. Type I comorbidities are those that increase the risk of the disease of interest; Type II comorbidities have no causal link to the disease of interest but are, nonetheless, highly correlated with that disease; Type III comorbidities are illnesses that the disease of interest may cause, and Type IV are comorbidities that have no causal link to the disease of interest and are only weakly correlated with that disease. Two-part models are used to estimate the direct costs of rheumatoid arthritis and diabetes mellitus using 2000-2007 Medical Expenditure Panel Survey data. RESULTS: COI estimates are sensitive to the specification of comorbidities. The odds of incurring any expenses varies by 71% for diabetes mellitus and by 27% for rheumatoid arthritis, while conditional expenditures (e.g., expenditures among subjects incurring at least some expenditures) vary by 62% and 45%, respectively. Uncertainty in prevalence rates cause costs to vary. A sensitivity analysis estimated the COI for diabetes ranges from $131.7-$172.0 billion, while rheumatoid arthritis varies from $12.8-$26.2 billion. CONCLUSIONS: The decision to include Type II and Type III comorbidities is crucial in COI studies. Alternative models should be included with and without the Type III comorbidities to gauge the range of cost effects of the disease. In generating costs, alternative values for prevalence rates should be used and a sensitivity analysis should be performed.
24515649 CASPASE-12 and rheumatoid arthritis in African-Americans. 2014 Apr CASPASE-12 (CASP12) has a downregulatory function during infection and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal-Wallis non-parametric ANOVA with Mann-Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint-narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA patients.
23314687 Impact of managed care health insurance system for indigent patients with rheumatoid arthr 2013 Jun The aim of this study was to determine the clinical outcome among indigent patients with rheumatoid arthritis (RA) in Puerto Rico receiving their healthcare in a managed care system, as compared with non-indigent patients treated in fee-for-service settings. A cross-sectional study was conducted in 214 Puerto Ricans with RA (per American College of Rheumatology classification criteria). Demographic features, health-related behaviors, cumulative clinical manifestations, disease activity (per disease activity score 28), comorbid conditions, functional status (per Health Assessment Questionnaire), and pharmacologic profile were determined. Data were examined using uni- and multivariable (logistic regression) analyses. The mean (standard deviation (SD)) age of the study population was 56.6 (13.5) years; 180 (84.1 %) were women. The mean (SD) disease duration was 10.8 (9.6) years. Sixty-seven patients were treated in the managed care setting, and 147 patients received their healthcare in fee-for-service settings. In the multivariable analyses, RA patients treated in the managed care setting had more joint deformities, extra-articular manifestations, arterial hypertension, type 2 diabetes mellitus, cardiovascular events, fibromyalgia syndrome, and poorer functional status while having a lower exposure to biological agents than those treated in fee-for-service settings. Efforts should be undertaken to curtail the gap of health disparities among these Hispanic patients in order to improve their long-term outcomes.
25483781 Early prediction of rheumatoid arthritis by magnetic resonance imaging in the absence of a 2015 Nov OBJECTIVE: To assess the practicability of magnetic resonance imaging (MRI) in confirming the diagnosis of clinically suspected rheumatoid arthritis (RA), when anti-cyclic citrullinated peptide antibody and radiographic erosions are absent. METHODS: We prospectively involved 31 treatment-naive patients with early inflammatory arthritis. At the initial visit, X-rays and gadolinium-enhanced MRI of both hands, as well as serological examinations and acute phase reactants were performed. The scores of synovitis, bone edema, bone erosion and tenosynovitis of metacarpophalangeal and wrist joints were evaluated using the RA-MRI scoring system. For all the patients, radiographs at baseline were normal and anti-cyclic citrullinated peptide antibodies were negative. RESULTS: At the end of follow-up(median 15 months, range 12-20 months), 22 patients were diagnosed as having RA according to 1987 American College of Rheumatology criteria. Bone edema, erosions, synovitis and tenosynovitis were observed in all the patients. However, the frequency of symmetric synovitis in wrists was significantly higher in the RA group. Moreover this group turned out to have significantly higher MRI bone erosion score in wrists. Further, receiver operating characteristic curve analysis revealed a positive wrist bone erosion score at 5, with a specificity of 78% and a sensitivity of 68%. There was no significant difference between the two groups with respect to metacarpophalangeal synovitis, metacarpophalangeal bone erosion, bone edema or tenosynovitis. CONCLUSION: MRI evidence of symmetric synovitis at wrist and a high bone erosion score at that site may assist in making an early diagnosis of RA in those patients who are negative for anti-cyclic citrullinated peptide antibody.
24323395 Costs for hospital care, drugs and lost work days in incident and prevalent rheumatoid art 2015 Apr OBJECTIVE: To estimate the costs related to hospital care, drug use and work loss in prevalent and incident patients with rheumatoid arthritis (RA), and to describe their distribution. METHODS: A cohort of prevalent patients with RA ≥18 years on Jan 1, 2010, was identified from the Swedish National Patient Register (requiring ≥2 visits listing RA) and the Swedish Rheumatology Quality Register, and followed until 31 December 2010. From the same registers, patients with the 1st visit listing RA in 2009, with a 2nd visit within 1 year, were identified to the incident cohort, and were followed for 1 year. Five sex-matched, age-matched, education-matched and county-matched general population comparators were sampled per patient with RA. Costs were retrieved from national registers. RESULTS: The mean annual cost, including productivity losses per patients with RA (n=49 829) aged 18-64 years was €23 147 versus €8364 (median €15 059 vs €277) per comparator. In patients with RA ≥65 years, the mean healthcare cost was €6438 versus €2773 (median €2458 vs €677) per comparator. 13% of the patients accounted for 50% of the cost. For the incident patients with RA (n=2695), the mean monthly cost increased from a level close to the comparators 1 year before register identification (18-64 years: €736 vs €644; ≥65 years: €192 vs €178), peaked the month following the identification date, and decreased to twice the cost of the comparators 1 year after diagnosis (18-64 years: €1252 vs €628; ≥65 years: €487 vs €230). CONCLUSIONS: The mean annual cost in patients with established RA, and mean monthly cost in newly diagnosed patients with RA, were 2-3 times higher than in the general population.