Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biological therapy: results from the pathobiology of early arthritis cohort (PEAC).

OBJECTIVE: To establish whether synovial pathobiology improves current clinical classification and prognostic algorithms in early inflammatory arthritis and identify predictors of subsequent biological therapy requirement. METHODS: 200 treatment-naïve patients with early arthritis were classified as fulfilling RA1987 American College of Rheumatology (ACR) criteria (RA1987) or as undifferentiated arthritis (UA) and patients with UA further classified into those fulfilling RA2010 ACR/European League Against Rheumatism (EULAR) criteria. Treatment requirements at 12 months (Conventional Synthetic Disease Modifying Antirheumatic Drugs (csDMARDs) vs biologics vs no-csDMARDs treatment) were determined. Synovial tissue was retrieved by minimally invasive, ultrasound-guided biopsy and underwent processing for immunohistochemical (IHC) and molecular characterisation. Samples were analysed for macrophage, plasma-cell and B-cells and T-cells markers, pathotype classification (lympho-myeloid, diffuse-myeloid or pauci-immune) by IHC and gene expression profiling by Nanostring. RESULTS: 128/200 patients were classified as RA1987, 25 as RA2010 and 47 as UA. Patients classified as RA1987 criteria had significantly higher levels of disease activity, histological synovitis, degree of immune cell infiltration and differential upregulation of genes involved in B and T cell activation/function compared with RA2010 or UA, which shared similar clinical and pathobiological features. At 12-month follow-up, a significantly higher proportion of patients classified as lympho-myeloid pathotype required biological therapy. Performance of a clinical prediction model for biological therapy requirement was improved by the integration of synovial pathobiological markers from 78.8% to 89%-90%. CONCLUSION: The capacity to refine early clinical classification criteria through synovial pathobiological markers offers the potential to predict disease outcome and stratify therapeutic intervention to patients most in need.

Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune disease characterized by painful, swollen joints that can severely impair physical function and quality of life. The presenting symptoms of musculoskeletal pain, swelling, and stiffness are common in clinical practice, so familiarity with diagnosing and managing RA is crucial. Patients with RA are at greater risk for serious infection, respiratory disease, osteoporosis, cardiovascular disease, cancer, and mortality than the general population. In recent years, early diagnosis, aggressive treatment, and expanded therapeutic options of disease-modifying antirheumatic drugs have markedly improved both the management and long-term prognosis of RA.

Effect of iguratimod on diclofenac metabolism by CYP2C9 in rats and human recombinant CYP2C9 yeast cells

Iguratimod (IGU, also known as T-614), a novel disease modifying antirheumatic drug intended to cure patients with rheumatoid arthritis (RA). The purpose of this study is to evaluate the effect of IGU on the pharmacokinetics of CYP2C9 probe drug diclofenac and its metabolite 4′-hydroxy diclofenac in vivo and in vitro. In in vivo experiments, 24 rats were randomly assigned to three groups consisting of the control group (Normal saline), low dose IGU group (10 mg/kg) and high dose IGU group (30 mg/kg). Blood samples were collected from orbital sinuses vein before 1 hour and serial times of giving diclofenac (15 mg/kg) to all the rats. Plasma concentration of diclofenac and its metabolite 4´-hydroxy diclofenac were assayed by high performance liquid chromatography. Pharmacokinetic parameters were assessed by Winnonlin 6.4 pharmacokinetic software. Moreover, in vitro studies were performed in recombinant human CYP2C9 yeast cell system. IGU at low dose showed no significant differences in the pharmacokinetic parameters of diclofenac and 4-hydroxy diclofenac in vivo when compared with control group (p>0.005). However, at the high dose of IGU, the pharmacokinetic parameters of 4´-hydroxy metabolite of diclofenac increase in half-life (T1/2) and mean area under the curve (AUC0→24), while a decrease in mean clearance (CL, mL/h/kg) and volume of distribution Vz (mL/kg). In addition, in in vitro study, high doses of IGU reduces the metabolism rate of diclofenac. IGU at high dose significantly increase the pharmacokinetics parameters of 4´-hydroxy diclofenac in rats. Additionally, it also showed the potent inhibitory effect on diclofenac metabolism in recombinant human CYP2C9 yeast cells.

[Chinese medical syndromes of rheumatoid arthritis: a clinical literature study].

OBJECTIVE: To explore the distribution features of Chinese medical syndromes of rheumatoid arthritis (RA) by literature retrieval. METHODS: Pertinent articles on treating RA by syndrome differentiation were retrieved from China National Knowledge Infrastructure Databases (CNKI), VIP Chinese Biomedical Journal Database, Guizhou Digital Library, and Duxiu Chinese Academic Periodicals full papers database from January 2000 to December 2011. RESULTS: A total of 33 documents were recruited covering 4 233 cases. Damp-heat blocking collaterals syndrome occupied the top in the occurrence frequency (20 times, 60.61%), followed by deficiency of Gan and Shen syndrome (18 times, 54.55%), intermingled phlegm and blood-stasis syndrome (17 times, 51.52%), wind-cold-damp impediment syndrome (15 times, 45.45%), cold-damp blocking collaterals syndrome (14 times, 42.42%), wind-damp-heat impediment and deficiency of qi and blood syndrome (10 times, 30.30%), and intermingled cold and heat syndrome (9 times, 27.27%). According to the case number of patients, it was sequenced as damp-heat blocking collaterals syndrome syndrome (768 cases, 18.14%), wind-damp-heat impediment syndrome(666 cases, 15.73%), wind-cold-damp impediment syndrome(584 cases, 13.80%), cold-damp blocking collaterals syndrome syndrome (517 cases, 12.21%), intermingled cold and heat syndrome (415 cases, 9.80%), intermingled phlegm and blood-stasis syndrome (364 cases, 8.60%), deficiency of Gan and Shen syndrome (235 cases, 5.55%),asthenia of healthy energy due to lingering arthralgia syndrome (223 cases, 5.27%). The case numbers of remaining syndromes did not exceed 5%. CONCLUSION: Damp-heat blocking collaterals syndrome was the main syndrome in RA patients, followed by wind-cold-damp impediment syndrome,wind-damp-heat impediment syndrome,cold-damp blocking collaterals syndrome,intermingled phlegm and blood-stasis syndrome, and deficiency of Gan and Shen syndrome.

South African recommendations for the management of rheumatoid arthritis: an algorithm for the standard of care in 2013.

Updated treatment recommendations for the therapy of rheumatoid arthritis (RA) in South Africa advocate early diagnosis, prompt initiation of disease-modifying anti-rheumatic drugs (DMARDs), and an intense treatment strategy where disease activity is assessed with a composite score such as the Simplified Disease Activity Index (SDAI). Frequent assessments and escalation of therapy are necessary until low disease activity (LDA) (SDAI ≤11) or ideally remission (SDAI ≤3.3) is achieved. Synthetic DMARDs may be used as monotherapy or in combination, and can be co-prescribed with low-dose corticosteroids if necessary. Biologic DMARD therapy should be considered for patients who have failed a 6-month trial of at least 3 synthetic DMARDs. All RA patients in SA are at increased risk of tuberculosis (TB), in particular patients using anti-tumour necrosis factor (TNF) biologic therapy. These recommendations provide practical suggestions for the screening and management of TB and other comorbidities, and offer an approach to monitoring of RA patients.

The new ACR/EULAR classification criteria for RA: how are the new criteria performing in the clinic?

The objective of the 2010 ACR/European League Against Rheumatism classification criteria for RA was to distinguish patients at high risk for developing persistent erosive and/or inflammatory disease from those with undifferentiated inflammatory arthritis. These criteria were developed for use in clinical trials; in order to implement these criteria most effectively, they need to be validated in real-world settings. The 1987 criteria may have led to underdiagnosis in the case of patients with positive anti-citrullinated peptide antibody values but no evidence of radiographic progression of joint erosion, or overdiagnosis in the case of some patients with FM; similarly, the possibility that the 2010 criteria may result in overdiagnosis cannot be excluded. Prospective validation of the 2010 criteria has been carried out in several cohorts, with reported sensitivities ranging from 0.50 to 0.60 and specificities from 0.88 to 0.97. The sensitivity and specificity of the 2010 criteria were 0.74 and 0.66 when compared against the gold standard of needing MTX therapy in the opinion of experienced clinicians, and 0.69 and 0.72 against the standard of having persistent synovitis despite DMARDs after 1 year. Other comparisons have yielded similar sensitivities and specificities, ranging up to 0.85 for the gold standard of needing MTX therapy. Questions remain concerning the utility of the 2010 criteria for non-arthritis health care practitioners, who may be less than expert in identifying swollen joints and may underestimate the number of joints affected by synovitis. US may be of value in the future, but its role remains to be validated.

Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.

OBJECTIVE: The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies. METHODS: In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chinese medicine expert classified each RA patient as a Cold or Heat type according to Chinese medicine theory. Multivariate data analysis techniques are employed to detect and validate biochemical and symptom relationships with the classification. RESULTS: The questionnaire items 'Red joints', 'Swollen joints', 'Warm joints' suggest differences in the level of inflammation between the groups although c-reactive protein (CRP) and rheumatoid factor (RHF) levels were equal. Multivariate analysis of the urine metabolomics data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than in the Heat RA patients, suggesting differences in muscle breakdown. Additionally, higher dehydroepiandrosterone sulfate (DHEAS) levels in Heat patients compared to Cold patients were found suggesting that the Cold RA group has a more suppressed hypothalamic-pituitary-adrenal (HPA) axis function. CONCLUSION: Significant and relevant biochemical differences are found between Cold and Heat RA patients. Differences in immune function, HPA axis involvement and muscle breakdown point towards opportunities to tailor disease management strategies to each of the subgroups RA patient.

Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry.

Rheumatoid arthritis (RA) is the most severe type of chronic inflammatory disease and has always been a research hotspot in different fields. In this study, a non-targeted metabonomics approach was carried out to profile metabolic characteristics of RA and its Chinese medicine subtypes by using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Plasma samples of 57 RA patients and 23 healthy controls were collected. On the basis of the traditional Chinese medicine (TCM), RA patients were classified into two main patterns, the cold pattern and the heat pattern. By using univariate and multivariate data analysis, we found that the RA patients presented diverse dysfunctions in inositol phosphate metabolism, lipid metabolism, amino acid metabolism, glucose metabolism, ascorbate metabolism, glyoxylate and dicarboxylate metabolism. The metabolic phenotypes were different between the RA cold pattern and the RA heat pattern. Compared with the RA cold pattern, the RA heat pattern showed elevated plasma concentrations of glycochenodeoxycholate, proline, saturated and mono-unsaturated phosphatidylcholine (PC) but decreased levels of urea, free fatty acid (FFA) and polyunsaturated PC. Our data show that metabonomics is a valuable tool in disease and TCM subtype research.

Identification and evaluation of novel synovial tissue biomarkers in rheumatoid arthritis by laser scanning cytometry.

INTRODUCTION: Suitable biomarkers are essential for therapeutic strategies in personalized medicine in terms of diagnosis as well as of prognosis. With highly specific biomarkers, it is possible, for example, to identify patients with poor prognosis, which enables early intervention and intensive treatment. The aim of this study was to identify and validate biomarkers and possible combinations for a prospective use in immunoscintigraphy, which may improve diagnosis of rheumatoid arthritis (RA) patients with consideration of inflammatory activity in the affected joints. Therefore, we tested several monoclonal antibodies (mAbs) directed against cellular-surface molecules on cells likely to be involved in the pathogenesis of RA. METHODS: Synovial tissue from patients with long-standing RA (accompanied by synovitis with varying states of current activity) and patients with acute non-RA arthritis were stained for surface molecules on different cell types by using fluorochrome-labeled antibodies. Tissue analysis was done by laser scanning cytometry (LSC), and statistical evaluation, by discriminant analysis and ROC analysis. RESULTS: CD11b, HLA-DR, CD90, and CD64 revealed significant differences between tissues from patients with RA and acute non-RA arthritis. Especially with the expression of CD64, both patient cohorts could be discriminated with high sensitivity and specificity. RA classification was improved by simultaneously investigating the expression of two or three different surface proteins, such as HLA-DR, CD90, and CD29 in the tissue. The simultaneous analysis of CD64 together with CD304 or the combination of CD11b and CD38 was suitable for the identification of RA patients with high current activity in synovitis. CONCLUSIONS: In this study, we showed that LSC is a novel reliable method in biomarker prevalidation in RA. Hence, identified mAbs in situ may allow their potential use in in vivo approaches. Moreover, we proved that biomarker-combination analysis resulted in better discrimination than did single-marker analysis. Combinations of these markers make a novel and reliable panel for the discrimination between RA and acute non-RA arthritis. In addition, further expedient combinations may be novel promising biomarker panels to identify current activity in synovitis in RA.

Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis.

Clinical manifestations of rheumatoid arthritis (RA) are diversified, and based on the manifestations, the patients with RA could be classified into different patterns under traditional Chinese medicine. These patterns decide the selection of herbal prescription, and thus they can help find a subset of rheumatoid arthritis patients for a type of therapy. In the present study, we combine genome-wide expression analysis with methods of systems biology to identify the functional gene networks for the sets of clinical symptoms that comprise the major information for pattern classification. Clinical manifestations in rheumatoid arthritis were clustered with factor analysis, and two factors (similar to cold and hot patterns in traditional Chinese medicine) were found. Microarray technology was used to reveal gene expression profiles in CD4(+) T cells from 21 rheumatoid arthritis patients. Protein-protein interaction information for these genes from databases and literature data was searched. The highly-connected regions were detected to infer significant complexes or pathways in this protein-protein interaction network. The significant pathways and function were extracted from these subnetworks using the Biological Network Gene Ontology tool. The genes significantly related to hot and cold patterns were identified by correlations analysis. MAPK signalling pathway, Wnt signaling pathway, and insulin signaling pathway were found to be related to hot pattern. Purine metabolism was related to both hot and cold patterns. Alanine, aspartate, and tyrosine metabolism were related to cold pattern, and histindine metabolism and lysine degradation were related to hot pattern. The results suggest that cold and hot patterns in traditional Chinese medicine were related to different pathways, and the network analysis might be used for identifying the pattern classification in other diseases.

[The objectivity research on 322 rheumatoid arthritis patients of dampness-heat impeding and cold-dampness impeding Chinese medical syndrome types].

OBJECTIVE: To analyze the Chinese medical syndrome typing laws in rheumatoid arthritis (RA) patients of the dampness-heat impeding syndrome and the cold-dampness impeding syndrome. METHODS: Clinical data and serum of 322 inpatients and outpatients were collected to perform DAS28 score. Laboratory indices including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin (ALB), globulin (GLB), and blood routines (white blood cell, red blood cell, and platelet) were tested by conventional methods, and the serum levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were detected by ELISA. The difference of each index was analyzed between RA patients of the dampness-heat impeding syndrome and the cold-dampness impeding syndrome. RESULTS: The levels of DAS28 scores, ESR, CRP, white blood cell count, and platelet of RA patients of the dampness-heat impeding syndrome were significantly higher than those of the cold-dampness impeding syndrome (P <0.01). The serum level of GLB of RA patients of the dampness-heat impeding syndrome was obviously higher than that of the cold-dampness impeding syndrome (P <0.01), while the serum ALB level of RA patients of the dampness-heat impeding syndrome was obviously lower than that of the cold-dampness impeding syndrome (P<0.01). Compared with the dampness-heat impeding syndrome, ROC curve results showed the area under the curve (AUC) were ranked from large to small as DAS28 score > ESR >CRP >GLB > PLT >WBC (P<0.01). Compared with the cold-dampness impeding syndrome, only ALB was of diagnostic value for cold-dampness impeding syndrome and the AUC was 0.636 (P = 0.000). CONCLUSION: DAS28 score, ESR, CRP, PLT, WBC, GLB, and ALB could be used as objective index in identifying the differences between the dampness-heat impeding syndrome and the cold-dampness impeding syndrome in RA patients.

[Rheumatoid arthritis: milestones in classification and treatment]. / Rheumatoide Arthritis - Meilensteine für Klassifikation und Therapie.

New classification criteria of rheumatoid arthritis (RA) by the American College of Rheumatology and the European League Against Rheumatism (EULAR) allow the early assignment of arthritides as RA and thus early start of therapy. This is an important step towards early diagnosis and treatment. The EULAR recommendations for the treatment of RA for the first time define the value of biologicals by means of therapeutic algorithms based on extensive scientific evidence and taking into account cost-effectiveness. As a result biologicals can be used after the first failure of disease-modifying anti-rheumatic drugs (DMARDs), if there are unfavourable prognostic factors. Methotrexate is, as a DMARD, at the centre of treatment.

Rheumatoid arthritis.

Rheumatoid arthritis is characterised by persistent synovitis, systemic inflammation, and autoantibodies (particularly to rheumatoid factor and citrullinated peptide). 50% of the risk for development of rheumatoid arthritis is attributable to genetic factors. Smoking is the main environmental risk. In industrialised countries, rheumatoid arthritis affects 0·5-1·0% of adults, with 5-50 per 100 000 new cases annually. The disorder is most typical in women and elderly people. Uncontrolled active rheumatoid arthritis causes joint damage, disability, decreased quality of life, and cardiovascular and other comorbidities. Disease-modifying antirheumatic drugs (DMARDs), the key therapeutic agents, reduce synovitis and systemic inflammation and improve function. The leading DMARD is methotrexate, which can be combined with other drugs of this type. Biological agents are used when arthritis is uncontrolled or toxic effects arise with DMARDs. Tumour necrosis factor inhibitors were the first biological agents, followed by abatacept, rituximab, and tocilizumab. Infections and high costs restrict prescription of biological agents. Long-term remission induced by intensive, short-term treatment selected by biomarker profiles is the ultimate goal.

Systems biology guided by Chinese medicine reveals new markers for sub-typing rheumatoid arthritis patients.

BACKGROUND: Complex chronic diseases such as rheumatoid arthritis have become a major challenge in medicine and for the pharmaceutical industry. New impulses for drug development are needed. OBJECTIVE: : A systems biology approach is explored to find subtypes of rheumatoid arthritis patients enabling a development towards more personalized medicine. METHODS: Blood samples of 33 rheumatoid arthritis (RA) patients and 16 healthy volunteers were collected. The RA patients were diagnosed according to Chinese medicine (CM) theory and divided into 2 groups, the RA Heat and RA Cold group. CD4 T-cells were used for a total gene expression analysis. Metabolite profiles were measured in plasma using gas chromatography/mass spectrometry. Multivariate statistics was employed to find potential biomarkers for the RA Heat and RA Cold phenotype. A comprehensive biologic interpretation of the results is discussed. RESULTS: : The genomics and metabolomics analysis showed statistically relevant different gene expression and metabolite profiles between healthy controls and RA patients as well as between the RA Heat and RA Cold group. Differences were found in the regulation of apoptosis. In the RA Heat group caspase 8 activated apoptosis seems to be stimulated while in the RA Cold group apoptosis seems to be suppressed through the Nrf2 pathway. CONCLUSIONS: RA patients could be divided in 2 groups according to CM theory. Molecular differences between the RA Cold and RA Heat groups were found which suggest differences in apoptotic activity. Subgrouping of patients according to CM diagnosis has the potential to provide opportunities for better treatment outcomes by targeting Western or CM treatment to specific groups of patients.

Does the Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for rheumatoid arthritis capture nursing practice? A Delphi survey.

BACKGROUND: The "Comprehensive ICF Core Set for Rheumatoid Arthritis (RA)" is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of patients with RA. OBJECTIVES: The objective of this study was to validate this ICF Core Set from the perspective of nurses. METHOD: Nurses experienced in RA treatment were asked about the patients' problems, patients' resources and aspects of environment that nurses take care of in a three-round survey using the Delphi technique. Responses were linked to the ICF. RESULTS: 57 nurses in 15 countries named 1170 concepts that covered all ICF components. 20 concepts were linked to the as yet undeveloped ICF component Personal Factors. 19 ICF categories are not represented in the Comprehensive ICF Core Set for RA. CONCLUSION: The validity of the Comprehensive ICF Core Set for RA was largely supported by the nurses. However, a number of body functions which address side effects of drug therapies were not included in the Comprehensive ICF Core Set for RA. Furthermore, several issues arose which were not precisely covered by the ICF like "dry mucous", "risk for decubitus ulcers" and "height" and need to be investigated further.

Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis: a nationwide case-control study in Denmark.

OBJECTIVE: To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs). METHODS: To address these issues, a nationwide case-control study was conducted in Denmark during 2002-2004, comprising incident cases of RA or patients with recently diagnosed RA (309 seropositive and 136 seronegative for IgG antibodies against CCP) and 533 sex- and age-matched population controls. Associations were evaluated by logistic regression analyses, in which odds ratios (ORs) served as measures of relative risk. RESULTS: Compared with individuals without SE susceptibility genes, SE homozygotes had an elevated risk of anti-CCP-positive RA (OR 17.8, 95% confidence interval [95% CI] 10.8-29.4) but not anti-CCP-negative RA (OR 1.07, 95% CI 0.53-2.18). Strong combined gene-environment effects were observed, with markedly increased risks of anti-CCP-positive RA in SE homozygotes who were heavy smokers (OR 52.6, 95% CI 18.0-154), heavy coffee drinkers (OR 53.3, 95% CI 15.5-183), or oral contraceptive users (OR 44.6, 95% CI 15.2-131) compared with SE noncarriers who were not exposed to these environmental risk factors. CONCLUSION: Persons who are homozygous for SE susceptibility genes, notably those who are also exposed to environmental risk factors, have a markedly and selectively increased risk of anti-CCP-positive RA. A distinction between anti-CCP-positive RA and anti-CCP-negative RA seems warranted, because these RA subtypes most likely represent etiologically distinct disease entities.

Generic quality-of-life assessment in rheumatoid arthritis.

BACKGROUND: Generic health status measures are commonly used in the evaluation of rheumatoid arthritis (RA) patients. The reliability, validity, and sensitivity of the instruments in the assessment of quality of life (QOL) in RA, and how they correlate to other clinical measurements, have long been questioned. OBJECTIVE: Analyze the performance of a commonly used generic health status measure, the Medical Outcomes Study 36-Item Short Form (SF-36), against the Outcome Measures in Rheumatology (OMERACT) criteria. METHODS: Data were analyzed from 7 double-blind, randomized controlled trials that examined the effectiveness of 1 or more interventions in RA. The primary outcome measures evaluated were the Mental and Physical Component Scores of the SF-36. Comparators were 1 or more of the following: the Health Assessment Questionnaire scores, tender joint count (TJC), the Disease Activity Score, and the American College of Rheumatology Responder Index (ACR20, ACR50, ACR70). The ability to detect a treatment effect in the study outcomes was evaluated using 3 measures: treatment difference, standardized response mean, and relative efficiency in relation to the TJC. RESULTS: As a generic QOL measure, the SF-36 is better suited to capture the holistic health of the patient, as reflected in the World Health Organization definition of health as being not only the avoidance of disease but the physical, emotional, and social well-being of the patient. Furthermore, use of the SF-36 permits comparisons of physical and mental aspects of QOL in the RA patient population, as well as comparisons of QOL parameters between patients with RA, other patient groups, and the general population. CONCLUSION: The SF-36 deserves serious consideration for inclusion in the core set of outcomes in RA trials.