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ID PMID Title PublicationDate abstract
17131100 [Shoulder prostheses]. 2006 Dec The design of shoulder prostheses has been developed through four generations which mirror adaptation to our increasing knowledge of the biomechanics of the shoulder joint. Modern shoulder prostheses are adapted to the size, inclination, posterior offset, and retrotorsion of the shoulder. The main reasons for implantation of a shoulder prosthesis are primary osteoarthritis, posttraumatic and rheumatoid arthritis, avascular necrosis, instability arthritis and cuff defect arthropathy. Typical implants are cup prostheses for surface replacement, anatomical stem prostheses, and reverse prostheses. Total prostheses are functionally better as soon as the arthritis involves the glenoid, whereas hemiprostheses should be preferred as long as the glenoid is intact. The stem is mostly cemented, whereas in younger patients with good bone quality a cementless stem may be used. Cemented glenoids may be considered as standard.
16255018 Relative contribution of cardiovascular risk factors and rheumatoid arthritis clinical man 2005 Nov OBJECTIVE: To estimate the contribution of cardiovascular (CV) risk factors and rheumatoid arthritis (RA) disease manifestations to atherosclerosis in RA. METHODS: We used high-resolution carotid ultrasound to measure the carotid intima-media thickness (IMT) and plaque in 631 RA patients. Using R(2) measures from multivariable models, we estimated the contribution of demographic characteristics (age, sex, and ethnic group), CV risk factors (diabetes mellitus, hypercholesterolemia, cigarette smoking, hypertension, and body mass index, and RA manifestations (joint tenderness, swelling, and deformity, nodules, erythrocyte sedimentation rate [ESR], C-reactive protein, rheumatoid factor, the HLA-DRB1 shared epitope, and cumulative glucocorticoid dose) to each of the outcomes. Estimates were obtained in the full sample, and within strata defined by age, sex, and ethnic group. We tested for interaction between CV risk factors and RA manifestations. RESULTS: The contribution of demographic factors, CV risk factors, and RA manifestations to IMT and plaque R(2) varied depending on the patients' age stratum. Demographic features explained 11-16% of IMT variance, CV risk factors explained 4%-12%, and RA manifestations explained 1-6%. The greatest contribution of RA manifestations occurred in the youngest age group, while that of CV risk factors occurred in the older age groups. Results for carotid plaque were similar. There was a significant interaction between the number of CV risk factors present and the ESR, suggesting that the ESR's effect on IMT varied according to the number of CV risk factors. CONCLUSION: Both established CV risk factors and manifestations of RA inflammation contribute significantly to carotid atherosclerosis in RA, and may modify one another's effects. These findings may have implications regarding the prevention of atherosclerosis in RA.
16855155 Revisiting the toxicity of low-dose glucocorticoids: risks and fears. 2006 Jun We have recently participated in a careful literature search and critical evaluation of glucocorticoids, and we have revised the side-effects data of four recent controlled trials of low-dose glucocorticoids (GCs) in rheumatoid arthritis. The toxicity profile stands out as remarkably more benign than expected from most textbook recommendations. Data regarding low-dose therapy are scarce and of low quality, as no controlled trials have been designed to specifically address toxicity. Common fears of GC toxicity seem to originate from an excessive weight on anecdotal data and observations with high doses, as in organ transplantation. There is now evidence that mechanisms of action of GCs vary considerably according to the dose, thus allowing the possibility of a different toxicity profile. Data from recent controlled trials are quite reassuring, overall. Certainly, risks and benefits of GCs need to be carefully weighed in every patient. But we need to make a clear distinction between established risks and unchecked fears while trying to get the best result for our patient. Clearly, there is a need for studies that are appropriately designed to address the toxicity of GCs and to avoid the risk of "throwing out the baby with the bath water."
16206340 Household income and earnings losses among 6,396 persons with rheumatoid arthritis. 2005 Oct OBJECTIVE: Rheumatoid arthritis (RA) causes disability and reduced productivity. There are no large quantitative studies of earnings and productivity losses in patients with clinical RA, and no studies of household income losses. We describe methods for obtaining earnings and household income losses that are applicable to working as well as nonworking RA patients, and we perform such studies using these methods. METHODS: We estimated cross-sectional expected annual earnings and household income losses in 6,649 persons with RA from Current Populations Survey (CPS) and O*NET (Occupational Information Network) data, and we estimated expected household income and earnings losses based on demographic characteristics after adjustment to Medical Outcomes Study Short-Form 36 (SF-36) population norms (internal method). Workplace productivity was measured by the Work Limitations Questionnaire (WLQ). RESULTS: 27.9% of patients aged < or = 65 years considered themselves disabled after 14.6 years of RA, and 8.8% received disability benefits. Annual earnings losses ranged between USD 2,319 and USD 3,407 by the CPS and internal method (preferred), with losses of 9.3% and 10.9%. A 0.25 difference in Health Assessment Questionnaire (HAQ) score was associated with a $1,095 difference in annual earnings. Productivity losses were 6% based on work limitations identified by the WLQ. Household income loss (percentage loss) including transfer payments was USD 6,287 (11.8%) for all patients, USD 4,247 (6.9%) for employed patients, and USD 7,374 (14.8%) for nonworking patients. Among nonworking nondisabled patients aged < or = 65 years, income loss was 14.1%. CONCLUSION: As measured by annual household income loss, the overall impact of RA is USD 6,287 (11.8%). Earnings and household income are dependent on functional status, education, age, ethnicity, and marital status. Income loss is predicted by the HAQ, HAQ-II, Modified HAQ, and SF-36.
15742462 Effects of infliximab treatment on rheumatoid synovial tissue. 2005 Mar Several studies have shown decreased synovial inflammation after treatment of patients with rheumatoid arthritis (RA) with infliximab. Recent data indicate that these effects can be detected as soon as 48 hours after first infusion. Although there are strong indications that infliximab exerts its effects in patients with Crohn's disease by induction of apoptosis in the gut, there are as yet no studies that convincingly show the same mechanism of action in RA. Conceivably, neutralization of tumor necrosis factor-alpha may be sufficient to induce clinical improvement in RA, even without induction of apoptosis at the site of inflammation. This hypothesis could explain the observation that both infliximab and etanercept are effective in RA, whereas apoptosis induction by infliximab might be required in Crohn's disease. Future studies should focus on the evaluation of apoptosis within the first 48 hours after initiation of therapy in RA to exclude the possibility that the effects occur very early after infliximab infusion.
16986268 Systems biology for battling rheumatoid arthritis: application of the Entelos PhysioLab pl 2005 Dec A large-scale mathematical model, the Entelos Rheumatoid Arthritis (RA) PhysioLab platform, has been developed to describe the inflammatory and erosive processes in afflicted joints of people suffering from RA. The platform represents the life cycle of inflammatory cells, endothelium, synovial fibroblasts, and chondrocytes, as well as their products and interactions. The interplay between these processes culminates in clinically relevant measures for inflammation and erosion. The simulation model is deterministic, which allows tracing back the mechanism of action for a particular simulation result. Different patient phenotypes are represented by different virtual patients. The RA PhysioLab platform has been used to systematically and quantitatively study the predicted therapeutic effect of modulating several molecular targets, which resulted in a ranking of putative drug targets and a workflow to confirm the simulations experimentally. In addition, critical pathways were identified that drive the predicted disease outcome. Within these pathways, targets were identified from public literature that were not previously associated with arthritis. The model provides insights into the biology of RA and can be used as a platform for hypothesis-driven research. Case studies of therapies directed against IL-12 and IL-15 illustrate the approach, with emphasis on the analysis of system dynamics.
16906371 Doppler sonographic comparative study on usefulness of synovial vascularity between knee a 2006 We used Doppler sonography to evaluate the therapeutic effects of infliximab on the knee and metacarpophalangeal (MCP) joints of 10 patients with rheumatoid arthritis (RA), based on the color flow signals (CFS) and resistance index (RI) of synovial vascularity. After three injections of infliximab, we observed significant improvement in numbers of tender joints (P < 0.01), values of C-reactive protein (CRP) (P < 0.01), erythrocyte sedimentation rate (ESR) (P < 0.001), disease activity scores including tender joints, swollen joints, and ESR (DAS28-E3) (P < 0.0001), and CFS of knee (P < 0.001) and MCP (P < 0.05) joints. There was no significant improvement in RI values of knee or MCP joints after the therapy. We observed significant correlation between CFS of knee joints (knee-CFS) and values of CRP (P < 0.01), ESR (P < 0.01), and DAS28-E3 (P < 0.05), but not between CFS of MCP joints (MCP-CFS) and values of CRP, ESR, and DAS28-E3. However, no significant correlation was observed between 10 difference values (before values-after values) of CFS grades of knee or MCP joints and 10 difference values each of CRP, ESR, or DAS28-E3. The knee joints are more suitable than MCP joints for obtaining CFS in Doppler sonography, and are more useful than MCP joints for evaluation.
15899057 Regulatory T cells in rheumatoid arthritis. 2005 Apart from the deletion of autoreactive T cells in the thymus, various methods exist in the peripheral immune system to control specific human immune responses to self-antigens. One of these mechanisms involves regulatory T cells, of which CD4+CD25+ T cells are a major subset. Recent evidence suggests that CD4+CD25+ T cells have a role in controlling the development of autoimmune diseases in animals and in humans. The precise delineation of the function of CD4+CD25+ T cells in autoimmune inflammation is therefore of great importance for the understanding of the pathogenesis of autoimmune diseases. Moreover, the ability to control such regulatory mechanisms might provide novel therapeutic opportunities in autoimmune disorders such as rheumatoid arthritis. Here we review existing knowledge of CD4+CD25+ T cells and discuss their role in the pathogenesis of rheumatic diseases.
16390820 Edaravone inhibits rheumatoid synovial cell proliferation and migration. 2006 Feb Rheumatoid arthritis (RA) is characterized by synovial proliferation and migration which is induced by proinflammatory cytokines or oxidative stress, followed by joint destruction. Edaravone, clinically available free radical scavenger in Japan, is confirmed to be beneficial in the acute stage of cerebral infarction. We aimed to investigate whether edaravone suppressed in vitro proliferation and migration of synovial cells (SC) induced by IL-1beta. SC proliferation and migration induced by IL-1beta were dose-dependently suppressed by edaravone at the clinically available concentration. These data suggest that edaravone has potential effects to suppress SC proliferation and migration, followed by suppression of synovial proliferation in RA. Therefore, edaravone, an antioxidant agent, might be a novel therapeutic agent which develops the new strategy for treatment of RA, and more detailed studies are required to establish the therapeutic effect of edaravone on RA in vivo.
17065108 Purine metabolism and clinical status of patients with rheumatoid arthritis treated with d 2006 The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.
15901635 Muscle strength, pain, and disease activity explain individual subdimensions of the Health 2006 Jan OBJECTIVE: To study the extent to which muscle strength and performance, pain, and disease activity are associated with the total Health Assessment Questionnaire (HAQ) disability index and its subdimensions in male and female patients with rheumatoid arthritis. METHODS: HAQ for functional capacity was completed by 135 patients with rheumatoid arthritis referred for orthopaedic surgery (74% women; mean (SD) age 62 (10) years; disease duration 19 (13) years, 70% positive for rheumatoid factor). Knee extension, trunk extension and flexion, grip strength, walking speed, and sit-to-stand test were measured to mirror physical function. Radiographs of hands and feet, pain, and the modified 28 joint disease activity score (DAS28) were also assessed. RESULTS: Mean total HAQ was 1.08 (0.68) in women and 0.67 (0.70) in men (p = 0.0031). Women had greater disability than men in five of the eight subdimensions of the HAQ. Grip strength was 48%, knee extension strength 46%, trunk extension strength 54%, and trunk flexion strength 43% lower in women than in men. Knee extension strength was inversely correlated with walking time (r = -0.63 (95% confidence interval, -0.73 to -0.51)) and with sit-to-stand test (r = -0.47 (-0.60 to -0.31)). In an ordered logistic regression analysis in female rheumatoid patients, DAS28, pain, knee extension strength, and grip strength were associated with the total HAQ disability index. CONCLUSIONS: Women reported greater disability than men both in the total HAQ and in the majority of its eight subdimensions. In addition to disease activity and pain, muscle strength has a major impact on disability especially in female rheumatoid patients.
16206363 Minimal clinically important difference, low disease activity state, and patient acceptabl 2005 Oct The importance of determining a minimal clinically important difference (MCID) and a low disease activity state (LDAS) as treatment targets in clinical trials no longer needs to be demonstrated. However, many methodological issues remain: whether these thresholds should be defined for each criterion or for composite criteria, whether there is a difference between the LDAS and patient acceptable symptom state (PASS), how to determine these thresholds (i.e., the wording of the questions and the statistical approach), and whether there are confounding factors in their evaluation. We consider these methodological issues and discuss their impact. Methods to determine the thresholds must be standardized, and recommendations could be endorsed by an OMERACT module. Threshold values for the MCID and LDAS should be determined according to data-driven and experts' opinions and approaches.
16507117 PTPN22 polymorphism and anti-cyclic citrullinated peptide antibodies in combination strong 2006 We analysed relationships between the PTPN22 1858 polymorphism and antibodies to cyclic citrullinated peptide (CCP), rheumatoid factors (RFs) and the shared epitope (SE) gene (HLA-DRB1*0404 or 0401) and determined their combined predictive value for rheumatoid arthritis (RA) in individuals who subsequently developed RA. This case-control study was nested within the Medical Biobank of Northern Sweden. Patients with RA (n = 92) were identified from amongst blood donors antedating onset of disease by a median of 2.4 (interquartile range 1.2 to 4.9) years. Matched controls were selected randomly from the same cohorts (n = 368). Anti-CCP antibodies and RFs were determined using enzyme-linked immunoassays. Genotyping was performed using an ABI PRISM 7900HT instrument and HLA-SE genes were identified using PCR sequence-specific primers. The 1858T allele and also carriage of T were associated with future onset of RA (odds ratio (OR) = 2.29, 95% confidence interval (CI) 1.45-3.61 and OR = 2.64, 95% CI 1.56-4.47, respectively). The combination of the 1858T variant and anti-CCP antibodies gave 100% specificity for the disease. None of the 368 controls expressed this combination. The PTPN22 1858T variant and anti-CCP antibodies were clearly associated (OR = 3.80, 95% CI 1.51-9.57). A combination of the PTPN22 1858T variant and anti-CCP antibodies gave a much higher relative risk (>132.03) for developing RA than the combination of the T variant and HLA-SE (OR = 7.85). The PTPN22 1858T variant was associated with future development of RA. There was an association between the T variant and anti-CCP antibodies and their combination, found only among pre-patients, gives a very high relative risk for development of RA. The combination gave a specificity of 100% for diagnosing RA.
15940559 Effects of shoulder arthroplasty and exercise in patients with rheumatoid arthritis. 2005 Jun The aim of this study was to examine pain and shoulder function in patients with rheumatoid arthritis (RA) before and after shoulder arthroplasty and postoperative exercise. Twenty-four patients (26 shoulders) were consecutively included in a multicentre study. Before surgery, at discharge from hospital and after 3 and 6 months, perceived shoulder function and shoulder pain were assessed by visual analogue scales, activities of daily living by the Modified Health Assessment Questionnaire (M-HAQ) and shoulder range of motion (ROM) by a goniometer. All patients showed considerable pain reduction at discharge from hospital (p<0.001). In those with intact rotator cuff and biceps tendon (n=13) improvements were found after 6 months in active and passive abduction and flexion ROMs (p<0.01) and in M-HAQ (p<0.001). Such improvements were not found in those with torn soft tissue (n=12). Preoperatively, abduction and flexion motor deficits (passive ROM >active ROM) were found for the total group (p=0.001). Less flexion motor deficit was found in the intact soft tissue than in the torn soft tissue group after 3 (p=0.002) and 6 months (p<0.001). No group difference was found with respect to abduction motor deficit. In conclusion, pain relief was obtained by all patients. Improvements in ROMs and activities of daily living were influenced by the state of the soft tissue.
17165000 Efficacy profile of bucillamine in rheumatoid arthritis patients in a large observational 2006 Bucillamine (Buc) is a disease-modifying antirheumatic drug (DMARD) developed in Japan, which has been used as one of the first-line DMARDs for the treatment of rheumatoid arthritis (RA) in Japan. However, direct comparison of this drug with standard DMARDs including sulfasalazine (SASP) and methotrexate (MTX) has been scarcely reported. We therefore tried to evaluate the clinical efficacy of Buc by analyzing the database from the long-term observational cohort study IORRA (previously known as J-ARAMIS). The cross-sectional analysis revealed that responses to Buc treatment were better in males, patients with shorter duration of illness, and those who were rheumatoid factor-negative. In the longitudinal analysis, although there was no marked difference among the baseline variables of patients with Buc, SASP, and MTX, the percentage of patients exhibiting moderate or good response to treatment, as rated using the European League Against Rheumatism improvement criteria, was higher in the Buc group (41.0%) than in the MTX (32.6%) and SASP groups (25.6%). These data support Buc as a candidate for being a first-line drug for the treatment of patients with RA.
16542499 The validity of a rheumatoid arthritis medical records-based index of severity compared wi 2006 The objective of this work was to assess the convergent validity of a previously developed rheumatoid arthritis medical records-based index of severity (RARBIS) by comparing it with the 28-joint Disease Activity Score (DAS28). This study was conducted in subjects within the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS). We selected 100 patients with rheumatoid arthritis (RA) from the BRASS with DAS28 scores equally distributed in four quartiles. The medical records were reviewed to calculate the RARBIS, which includes indicators from the following categories: prior surgical history, radiologic and laboratory findings, clinical and functional status, and extra-articular manifestations. The Spearman correlation between the RARBIS and the DAS28 was assessed in the total study population and in relevant subgroups. We re-weighted on subscales and recalculated the RARBIS score. This was performed based on findings of correlations between the DAS28 and subscales; and also the result from a multiple linear regression with the DAS28 (as a dependent variable) and five subscales (as independent variables). The mean RARBIS was 4.36 (range 0-11). Among the total study cohort, the RARBIS was moderately correlated with the DAS28 (r = 0.41, 95% confidence interval [CI] 0.23-0.56). In subgroup analyses, including age, gender, rheumatoid factor status, and disease duration, we found no statistically significant differences in the correlations. After re-weighting, the correlation between the RARBIS and the DAS28 was somewhat improved (r = 0.48, 95% CI 0.31-0.62). In conclusion, the RARBIS correlated moderately well with the DAS28 in this population. The RARBIS has both face and convergent validity for patients with RA and relevant subgroups and may have application for medical records studies in patients with RA.
15958759 Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterran 2005 Jul BACKGROUND: Pyrin is a newly recognised intracellular regulator of inflammation, and mutations in MEFV, the gene encoding pyrin, are the cause of familial Mediterranean fever. OBJECTIVE: To determine if known mutations of MEFV are associated with rheumatoid arthritis (RA) morbidity or can modify RA severity. METHODS: The frequency of the three most common MEFV mutations: M694V, V726A, and E148Q, was determined in 98 Israeli patients with RA (74 women, 24 men) and compared with that in 100 healthy subjects matched for origin. RA severity was determined using a new clinical score of 126 grades. The median severity score of mutation carrier and non-carrier groups was compared after confounding measures were eliminated by logistic regression. RESULTS: 17/98 (17%) patients with RA (all women) were heterozygous for common MEFV mutations, predominantly E148Q (12 patients), and one patient was homozygous for the V726A mutation. The overall mutation rate was comparable between patients with RA and healthy subjects. Patients carrying a mutation had a higher median severity score than the non-carrier group (42 v 29, p = 0.0005). The logistic regression model assigned a 15-fold odds ratio for severe RA in carriers, after adjusting for sex, presence of rheumatoid factor, age at onset, and disease duration (n = 97, p = 0.01, 95% CI 1.74 to 128). CONCLUSION: MEFV, and particularly the E148Q mutation, is an independent modifier of the clinical manifestations of RA. This is the second Th1-type autoimmune disease in which MEFV mutations have been shown to aggravate the clinical status.
17058552 Rheumatoid arthritis: new developments in biologic therapy. 2006 Jun With the development of biologic agents our therapeutic approach to rheumatoid arthritis (RA) and inflammatory diseases in general, has dramatically changed within the last few years. Biologic technically means a substance as the product of biologic system and functionally as an agent that targets specific biologic molecule. Recently a number of endogenous antigens have been identified and these are known to activate CD4+ T cells leading to production of cytokines [interleukin (IL)-1, IL-6] and tumour necrosis factor (TNF)-alpha and immunoglobulins like rheumatoid factor and expression of osteoprotegerin ligands that stimulate osteogenesis leading to joint distruction. Rheumatologists and other practitioners are facing a remarkable wave of new therapies for RA like infliximab, adalimumab, atlizumab, etanercept, anakinra, prosorbacolumn, anti-IL-6 agents, IL-10 and inferferon-r. To date combination therapy of methotrexate plus a single biologic has been widely studied with synergistic effect. Etanercept and infliximab are two biologics available in India.
15752303 Successful treatment of a leg ulcer occurring in a rheumatoid arthritis patient under lefl 2005 Mar OBJECTIVE: We report the case of a leg ulcer in a rheumatoid arthritis (RA) patient under treatment with leflunomide, discuss the influence of the drug on the aetiopathogenesis of the ulcer and describe its successful treatment. CASE SUMMARY: A 68-year-old woman with a 12-year history of RA developed a leg ulcer after 4 months of leflunomide treatment. Other ulcerogenic factors were ruled out. There were some clinical hints for rheumatoid vasculitis. The ulcer was resistant to ambulant conservative phase adapted wound bed preparation and a split skin transplantation failed. After omission of leflunomide and washout procedure with cholestyramine a second split skin transplantation resulted in complete healing. DISCUSSION: Leflunomide inhibits the division of activated T cells and thus inhibits among others the production of proinflammatory cytokines and the adhesion of cells to the endothelium. These mechanisms may partly explain the possible influence of leflunomide on the perpetuation of the ulcer. Until now, occurrence of vasculitis and leg ulcers has been described in one case each for the novel immunomodulator leflunomide. No successful treatment of a leg ulcer under leflunomide has been described yet. Omission of leflunomide and a washout treatment in our case led to a complete healing. This may indicate a critical role of leflunomide in the maintenance of this slow healing ulcer. CONCLUSIONS: An association between leflunomide intake, occurrence of leg ulcers in RA patients and delayed wound healing should be considered.
16881109 Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients wi 2006 Aug OBJECTIVE: To analyze serum concentrations of matrix metalloproteinases (MMP) MMP-1, MMP-3, MMP-9, MMP-13, tissue inhibitors of MMP (TIMP) TIMP-1 and TIMP-2, and MMP/TIMP ratios in patients with early rheumatoid arthritis (RA) before and after 6 months of treatment with methotrexate (MTX). METHODS: The study group consisted of 30 patients with RA, not treated with disease modifying antirheumatic drugs or corticosteroids, with disease duration < 3 years. Twenty patients with osteoarthritis (OA) served as a control group. Analysis of serum concentrations of MMP and TIMP was based on a quantitative sandwich ELISA. RESULTS: Serum concentrations of MMP-1, MMP-3, MMP-9, and MMP-13 were higher in untreated patients with early RA than in OA patients (p < 0.001 in all cases). Serum levels of TIMP-1 and TIMP-2 dominated in the serum of RA patients compared with controls (p < 0.01 and p < 0.05, respectively). Ratios of MMP to TIMP were significantly higher in patients with early RA versus controls. Six months' treatment with MTX downregulated serum concentrations of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), MMP-13 (p < 0.01), and TIMP-1 (p < 0.05) in patients with RA. These changes were accompanied by significantly reduced ratios of MMP to TIMP. MTX treatment decreased markers of RA activity such as the number of painful and swollen joints, erythrocyte sedimentation rate, Disease Activity Score, and C-reactive protein. CONCLUSION: Patients with early RA are characterized by high serum concentrations of tissue-degrading metalloproteinases. Therapy with MTX resulted in clinical improvement and reduced serum MMP levels in patients with RA, confirming effectiveness of MTX in patients in early stages of the disease.