Browse

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

ID PMID Title PublicationDate abstract
10878293 Methotrexate use in rheumatoid arthritis. A Clinician's perspective. 2000 May Aminopterine, a precursor of methotrexate (MTX), was first used for the treatment of rheumatoid arthritis (RA) in 1951 [Gubner, R., 1951. Therapeutic suppression of tissue reactivity: I. Comparison of the effects of cortisone and aminopterin. Am. J. Med. Sci. 221, 169-175; Gubner, R., August, S., Ginsberg, V., 1951. Therapeutic suppression of tissue reactivity: II. Effect of aminopterin in rheumatoid arthritis and psoriasis. Am. J. Med. Sci. 221, 176-182.]. Corticosteroids, and to some extent cyclophosphamide, took MTX out of the rheumatologist's armamentarium until the late 1970s-early 1980s when the toxic profile of these compounds became apparent. By the mid 1980s, four randomized clinical trials (RCTs) had proven beyond doubt the beneficial effects of MTX when administered to patients with established disease who had failed to respond to other compounds such as gold salts and D-penicillamine [Thompson, R.N., Watts, C., Edelman, J., Esdaile, J., and Russell, A.S., 1984. A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J. Rheumatol. 11, 760-763; Andersen, P.A., West, S.G., O'Dell, J.R., Via, C.S., Claypool, R.G., and Kotzin, B.L., 1985. Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann. Intern. Med. 103, 489-496; Weinblatt, M.E., Coblyn, J.S., Fox, D.A., Fraser, P.A., Holdsworth, D.E., Glass, D.N., and Trentham, D.E., 1985. Efficacy of low-dose methotrexate in rheumatoid arthritis. N. Engl. J. Med. 312, 818-822; Williams, H.J., Willkens, R.F., Samuelson, C.O.J., Alarcón, G.S., Guttadauria, M., Yarboro, C., Polisson, R.P., Weiner, S.R., Luggen, M.E., Billingsley, L.M., Dahl, S.L., Egger, M.J., Reading, J.C., and Ward, J.R., 1985. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum. 28, 721-730.]. Subsequently, these four trials were included in a meta-analysis and the drug was approved by the Food and Drug Administration for use in RA [Health and Public Policy Committee, H.P.P.C. and American College Physicians, A.C.P., 1987. Methotrexate in rheumatoid arthritis. Ann. Intern. Med. 107, 418-419; Paulus, H.E., 1986. FDA Arthritis Advisory Committee meeting: Methotrexate; guidelines for the clinical evaluation of antiinflammatory drugs; DMSO in scleroderma. Arthritis Rheum. 29, 1289-1290; Tugwell, P., Bennett, K., and Gent, M., 1987. Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy, and safety. Ann. Intern. Med. 107, 358-366.]. Since then, rheumatologists have become aware of what Pincus et al. have called "the side effects" of RA comparing the morbidity and mortality caused by RA with that potentially caused by medications used to treat this disease [Pincus, T. and Callahan, L.F., 1993. The "side effects" of rheumatoid arthritis: joint destruction, disability and early mortality. Br. J. Rheumatol. 32, 28-37.]. Thus, during the 1990s the use of MTX for the treatment of RA became generalized [O'Dell, J.R., 1997. Methotrexate use in rheumatoid arthritis. Rheum. Dis. Clin. N Am. 23, 779-796 (a); Bannwarth, B., Vernhes, J., Schaeverbeke, T., and Dehais, J., 1995. The facts about methotrexate in rheumatoid arthritis. Rev. Rhum. 62, 471-473 (b); Bologna, C., Jorgensen, C., and Sany, J., 1997a. Methotrexate as the initial second-line disease modifying agent in the treatment of rheumatoid arthritis patients. Clin. Exp. Rheumatol. 15, 597-601; Bologna, C., Viu, P. (ABSTRACT TRUNCATED)
9662753 A possible role for saliva as a diagnostic fluid in patients with chronic pain. 1998 Jun OBJECTIVES: The focus of this review was on proteins and peptides found in saliva. Of greatest interest were those neuropeptides relevant to nociception and to the pathogenesis of chronic pain syndromes. An additional goal was to develop a standardized protocol to collect saliva for laboratory assessment. METHODS: Data were obtained through discussion with experts at the medical schools in San Antonio and Heidelberg and a Medline literature search involving all relevant studies from 1966 to 1997. The literature search was based on the following key terms: saliva, serotonin, neuropeptide, substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF). RESULTS: The mean concentration of SP in the saliva of healthy normal controls ranged from 9.6 to 220 pg/mL. Generally, the concentration of SP was approximately three times higher in saliva than in plasma. In a number of painful conditions, particularly tension headache, substantial elevations of salivary SP were found. Mean values for salivary CGRP in healthy controls were approximately 22 pmol/L and were significantly elevated in patients with migraine attacks or cluster headache. There were no data to indicate prior quantitative determination of NGF in human saliva. CONCLUSIONS: After sampling and processing techniques have been standardized, measurement of neuropeptides in human saliva could provide a valuable tool for study of patients with chronic painful disorders such as rheumatoid arthritis, osteoarthritis, and even fibromyalgia syndrome.
9627017 The long-term outcomes of rheumatoid arthritis: a 23-year prospective, longitudinal study 1998 Jun OBJECTIVE: Although total joint arthroplasty (TJA) is a common procedure and an important outcome in rheumatoid arthritis (RA), little is known about its prevalence, failure rate, or predictors over the course of the illness. The current study evaluated these factors in 1,600 consecutive RA patients seen during a period of observation that extended 23 years. METHODS: Beginning in 1974, data from 34,040 RA patient visits were entered prospectively into a computer databank. Data consisted of laboratory, radiographic, physical examination, and self-report questionnaires. At each assessment, we also noted a complete surgical history. Patients were also followed up by questionnaires that were mailed at 6-month intervals. RESULTS: Kaplan-Meier life-table estimates indicated that 25% of RA patients will undergo total joint arthroplasty (TJA) within 21.8 years of disease onset. For patients with 1 TJA, 25% had a TJA in a different joint within 0.92 years and 50% within 7.0 years. Ten years after TJA, approximately 6% of implanted knees and 4% of implanted hips had been replaced with a second TJA, and 12% and 13% of the joints had either a second TJA or a TJA-related operation, respectively. In Cox regressions, a large series of clinical and laboratory variables, which primarily reflected disease activity, predicted TJA. Smoking, either past or present, had a protective effect. Patients with highly abnormal values on the Health Assessment Questionnaire Disability Scale, global severity, and erythrocyte sedimentation rate had a 3-6 times increased risk of TJA. CONCLUSION: TJA, a marker of joint failure and of RA outcome, is predicted by self-report assessments of severity and function, and by a series of laboratory, radiographic, and clinical variables. Prediction improves with the extent of observation, and 2-year observations approach full-study observations in their accuracy. Most TJAs survive for a long time in RA.
9535561 The cartilage collagens: a review of their structure, organization, and role in the pathog 1998 Mar This contribution reviews the structure and organization of collagen molecules found in cartilage and the roles that they may play in rheumatic diseases. Cartilage is unique in its physical properties and molecular composition, and contains sufficient amounts of types II, IX, X, and XI collagen to deem these molecules as "cartilage-specific." The vitreous body of the eye, a "cartilage-like" tissue is also rich in the same collagens but is type X deficient. Types VI and XII collagen are present in cartilage as well as noncartilaginous tissues. Types II, IX, and XI collagen are organized into matrix fibrils, where type II constitutes the bulk of the fibril, type XI regulates fibril size, and type IX facilitates fibril interaction with proteoglycan macromolecules. Genetic defects in these collagens can produce mild to severe developmental abnormalities, including spondyloepiphyseal dysplasia often accompanied by an accelerated form of osteoarthritis. Sensitization with collagen can produce experimental rheumatic diseases. Type II collagen induces an erosive polyarthritis in certain strains of rats, mice, and higher primates which can resemble rheumatoid arthritis and relapsing polychondritis. Type XI collagen is arthritogenic in rats but not mice; type IX induces autoimmunity in both species but not arthritis. Arthritis is initiated by complement fixing antibodies that bind to type II collagen in autologous cartilage, and the production of these antibodies is MHC restricted and T cell dependent. It is unclear whether T cells alone can induce arthritis, although they probably help sustain it. Mapping and characterizing the of T cell epitopes on type II collagen has resulted in the synthesis of small homolog and substituted peptides of type II collagen which suppress arthritis in an antigen-specific manner by a variety of routes, including mucosal. Moreover, collagen-induced arthritis has proven a valuable model to study the contribution of cytokines and other biological agents in the pathogenesis of joint injury and how they might be used to develop new therapies. Collagen autoimmunity has been implicated in the pathogenesis rheumatoid arthritis and polychondritis. Circulating antibodies to type II collagen are found in both diseases. Antibodies to types IX and XI collagen are also present in rheumatoid sera but are less prevalent. Rheumatoid cartilage and synovium contain antibodies to type II collagen at a prevalence far greater than serum, suggesting an intra-articular antigen-driven immune process. Although effective in animal models, attempts to treat rheumatoid arthritis with orally administered type II collagen have proven elusive. Different approaches using newer formulations and selected or modified oligopeptides remain to be tested and could prove effective in the treatment of the human rheumatic diseases.
11764201 Soluble CD154 in rheumatoid arthritis: elevated plasma levels in cases with vasculitis. 2001 Dec OBJECTIVE: To determine the levels of soluble CD154 (sCD154) in the plasma of patients with rheumatoid arthritis (RA) and rheumatoid vasculitis (RV). and to examine the relationship between the levels of sCD154 in plasma and the clinical variables. METHODS: Levels of sCD154 were quantified in 39 plasma samples from patients with RA, including 9 patients who were also diagnosed with RV, and compared with those of 20 healthy subjects. An ELISA was established and specificity of the ELISA was tested by control ELISA using isotype-matched IgG and preabsorption assay. The titers of IgM and IgG rheumatoid factor (IgM-RF, IgG-RF) for each patient were determined simultaneously, and values of other laboratory variables were also determined. RESULTS: Levels of sCD 154 in plasma were higher in patients with RA than in the healthy subjects (p < 0.02). Compared with RA patients without vasculitis, patients with RV had significantly higher levels of sCD154 in their plasma (p < 0.001). Control ELISA and absorption assay of sCD154 indicated that our ELISA system was capable of measuring plasma sCD154 in RA patients. Levels of sCD154 in RA plasma correlated significantly with both IgM-RF and IgG-RF titers (r = 0.64 and 0.61, respectively, both p < 0.001). The levels of sCD154 decreased after commencement of treatment for vasculitis in cases with RV. CONCLUSION: We identified the presence of sCD154 in RA plasma, with especially high levels in cases with vasculitis. Correlation between sCD154 and RF titers indicates the CD154-CD40 pathway is likely related to pathogenic RF production.
10479912 Onset of myasthenia gravis in a patient affected by rheumatoid arthritis never treated wit 1999 Jun We describe a patient affected by rheumatoid arthritis (RA) that developed myasthenia gravis (MG) after 20 years of illness. The peculiarity of this case concerns both the rare association between these diseases and the fact that the patients had never assumed disease modifying antirheumatic drugs. These treatments have been associated in some clinical reports with the onset of MG during the clinical course of RA. To our knowledge this is the first case described in medical literature up to now.
10587556 A preliminary study determining the feasibility of electromagnetic tracking for kinematics 1999 Dec OBJECTIVE: To determine the feasibility of using electromagnetic tracking (EMT) for quantifying three-dimensional kinematics at the ankle joint complex (AJC). METHODS: AJC kinematics were recorded in 10 normal healthy adults, and 10 rheumatoid arthritis patients presenting with AJC instability and deformity who were undergoing footwear and orthotic intervention. RESULTS: Kinematics in normal subjects had strong face validity, curve shape showing moderate (n=9), good (n=8) or excellent (n=4) agreement with data from seven published studies. The range of motion about the x-axis (15.2 degrees ) was similar to reference values (17.0 degrees ), but our technique underestimated rotations about the y- (8.1 degrees vs 14.0 degrees ) and z-axes (7.7 degrees vs 12.2 degrees ). In the rheumatoid arthritis pronated foot group, eversion and internal rotation during the stance phase of gait were between 2 and 5 times greater than for normal subjects. The use of a corrective foot orthosis in this group restored normal kinematics, reducing maximum eversion and internal rotation by 57 and 68%, respectively. CONCLUSION: A new technique for measuring kinematics at the AJC is described. Based upon the findings of this pilot study, EMT may be useful for diagnosing AJC dysfunction and quantifying the mechanical efficacy of footwear and orthosis interventions.
9709176 HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments. 1998 Apr OBJECTIVE: To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis. METHODS: Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401, 0404/0408, 0405, 0101, 1001, and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response. RESULTS: Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p < 0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p = 0.05). CONCLUSIONS: These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.
9189057 Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness 1997 May The EuroQol (EQ-5D) generic health index comprises a five-part questionnaire and a visual analogue self-rating scale. The questionnaire may be used as a health index to calculate a 'utility' value or as a health profile. The validity, reliability and responsiveness of EQ-5D were tested in 233 patients with rheumatoid arthritis stratified by functional class. EQ-5D demonstrated moderate to high correlations with measures of impairment and high correlations with disability measures. Stepwise regression models showed that EQ-5D utility values and visual analogue scores were explained best as a function of pain, disability, disease activity and mood (R2 approximately 70%), although other variables (side-effects, years of education) were required to explain the visual analogue scores. The EQ-5D health index and visual analogue scale are more responsive than any of the other measures, except pain and doctor-assessed disease activity. The reliability of the EQ-5D index and EQ-5D visual analogue scale is as good or better than that of all other instruments except the Health Assessment Questionnaire. Some patients with severe long-standing disease had health states which attracted utility values below zero, i.e. from a societal perspective they were regarded as being in states 'worse than death'. The practical and ethical implications of these utility valuations are discussed, and at present the utility values should be used and interpreted with caution. With this caveat, EQ-5D is simple to use, valid, responsive to change and sufficiently reliable for group comparisons. It is of potential use as an outcome measure in clinical trials, audit and health economic studies, but further work is required on its performance in other clinical contexts and on the interpretation of the utility values.
10189781 Impairment of quality of life: rheumatoid arthritis versus sarcoidosis. 1999 Mar BACKGROUND: Quality of life (QOL) has become an important item in health care. QOL should be a major target of treatment in chronic diseases such as rheumatoid arthritis (RA) and sarcoidosis. The aim of this study was to compare the impact of RA and sarcoidosis on patients' QOL. We expected more serious impairment of QOL in the RA group than in the sarcoidosis group. METHODS: QOL was studied in RA patients (n = 32), sarcoidosis patients (n = 37), and a healthy control group (n = 37) employing the World Health Organization Quality of Life assessment instrument (WHOQOL-100). RESULTS: In both patient groups QOL was impaired with respect to Physical Health, Level of Independence (P < 0.001), and Overall QOL and General Health (P < 0.01). Moreover, RA patients appeared to have a lower QOL with respect to Pain and Discomfort (P < 0.001) and Mobility (P < 0.001). CONCLUSIONS: In RA and sarcoidosis, fatigue and sleep were major problems. In contrast to our expectations, with respect to activities of daily living and working capacity, the two patient groups did not show any difference. Impairment of QOL was more serious and included more aspects of QOL in RA than in sarcoidosis.
9885910 Identification of the gene loci that predispose to rheumatoid arthritis. 1998 Dec We have searched the human genome for genes that predispose to rheumatoid arthritis (RA) using fluorescence-based microsatellite marker analysis and affected sib-pair linkage study. A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic microsatellite marker loci. Markers were amplified by the PCR using fluorescence-tagged primers and sized based on the difference of CA repeats on DNA. Linkage analysis was made using maximum lod score (MLS). The MLS for D1S214 and D8S556 was 3.27 and 3.33, while the MLS for the HLA-DRB1 region was <3.0. According to detailed analysis by single-point analysis using MAPMAKER/SIBS, the MLS for D1S253 and D1S214 was 3.77 and 3.58. The MLS by multipoint analysis was 6.13 for D1S253. The MLS for D8S556 by single-point analysis was 4.20. The MLS for DXS1232 was 2.35 by single-point analysis, whereas the MLS for the region 2 cM right to DXS1232 and the region between DXS1227 and DXS1200 was 3.03 and 2.93 by multi-point analysis. Three principal chromosome regions of linkage, D1S253/214, D8S556 and DXS1232, have been identified which we call RA1, RA2 and RA3 for RA disease loci.
10650535 Do cognitive processes predict mental health in individuals with rheumatoid arthritis? 1999 Dec The purpose of the present study was to assess the hypothesis that intellectual functioning affects the mental health of individuals with rheumatoid arthritis. Structural equation modeling techniques were used to assess the relative contributions of age, education, intellectual functioning, self-efficacy, and pain to mental health. It was hypothesized that individuals with rheumatoid arthritis who had higher intellectual functioning and higher self-efficacy would report better mental health than those with lower intellectual functioning and self-efficacy. One hundred twenty-one adults aged 34 to 84 with rheumatoid arthritis completed a battery of cognitive tasks, and multiple measures of self-efficacy, pain, and mental health, twice in 1 month. The data provided a good fit to the hypothesized model. Intellectual functioning was directly related to mental health and, also, indirectly related to mental health through self-efficacy and pain. Older individuals who performed poorly on cognitive tasks reported less self-efficacy, more pain, and poorer mental health than those individuals who performed well on cognitive tasks.
10403277 Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthr 1999 Jul OBJECTIVE: To examine the macroscopic vascular pattern of early synovitis in psoriatic arthritis (PsA), reactive arthritis (ReA), and rheumatoid arthritis (RA) and to assess the reliability of the grading features for synovitis. METHODS: Forty-four patients (14 PsA, 12 ReA, and 18 RA) with knee synovitis who were undergoing arthroscopy were assessed. Video recordings of the examination were scored independently by 3 arthroscopists who were blinded to the patient's identity and clinical details. Features of vascularity, villous formation, pannus, granularity, and capillary hyperemia were recorded and kappa values (-1 or =0.8) for features of vascularity, villous hypertrophy, and pannus. Seventy-three percent of the PsA and ReA patients had predominantly tortuous, bushy vessels; 89% of the RA patients had mainly straight, branching vessels. CONCLUSION: The distinct vascular patterns in PsA and ReA compared with those in RA may reflect different specific vascular factors in the pathogenesis of these arthritides. Vascularity and villous hypertrophy are the most reliable features of synovitis grading.
10494903 The participation of IL-8 in the synovial lesions at an early stage of rheumatoid arthriti 1999 May Synovial tissues from Rheumatoid Arthritis (RA) were divided into three groups based on their histopathological findings and compared for their expression of IL-8 and monocyte chemotactic and activating factor (MCAF) by using immunohistochemistry and in situ hybridization. The levels of IL-8 as well as those of MCAF were markedly higher in the synovial fluid from RA joints. Synovial lining cells (SLC) and macrophages had an ability to produce IL-8 at an early phase of the disease. The presence of MCAF was restricted in macrophages at this stage. On the other hand, the production of IL-8 as well as MCAF were prominent in most components of the joints such as SLC, migrated monocytes, sublining fibroblastoid cells, endothelial cells or migrated neutrophils at an active phase. The expression of IL-8 or MCAF was low in fibrotic synovitis of RA. These data indicate that IL-8 generated from SLC and macrophages may participate to the inflammatory process in the early synovitis of RA.
9623096 [Immunology in medical practice. XIV. Central nervous system complications in systemic aut 1998 Mar 7 Complications of the central nervous system (CNS) are common in systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome. Specific diagnostic tests are lacking and early intervention with immunosuppressive therapy is frequently necessary. Therefore knowledge of these CNS complications is essential for early diagnosis and treatment. Residual cognitive effects were observed in some but not in all tests after prolonged heavy cannabis use. The effects were mostly mild. The relationship of cannabis use, psychotic effects and schizophrenia was unclear; the cannabis conceivably gave relief, but it also appeared that cannabis caused schizophrenia in young people and (or) enhanced the symptoms, especially in young people poorly able to cope with stress or in whom the antipsychotic therapy was unsuccessful.
9289823 [Rational intra-articular corticosteroid injection]. 1997 May 31 The intraarticular injection of corticosteroids has been a well known and effective therapy for rheumatoid arthritis and swollen joints of other, non-infectious origin for almost 50 years. Today the indication for this intervention has to be more restrictive, and possible alternative therapies must be discussed with the patient. The number of injections in weight-bearing joints should not exceed three per year, and should no effect be noted, there is no reason to repeat an intraarticular injection. As there is a considerable variability in the details of administration of the injection, and the legal implications are currently changing, the practical aspects are discussed in this article. An extensive review of the literature leads to the distinction of actual knowledge from adopted faith and points out the relevant measures to minimize the risks and increase the benefits of the injection; most important is a precise and quick "no-touch"-technique. The restrictive indication and a standardized practical procedure are the basis for successful intraarticular injection of corticosteroids.
11072604 Bactericidal/permeability increasing protein and proinflammatory cytokines in synovial flu 2000 Sep OBJECTIVE: Bactericidal/permeability increasing protein (BPI) is a leukocyte product exerting antibacterial activity. Its production may be stimulated by cytokines, mainly Tumor Necrosis Factor (TNF) alpha. We studied BPI in the synovial fluid (SF) of psoriatic arthritis (PsA), a disease suspected to be influenced by infectious agents. METHODS: The levels of BPI and various indices of SF inflammation, including cytokines and its receptors, were determined in the SF of 18 patients with PsA and compared with those of 12 patients with rheumatoid arthritis (RA) and 9 with osteoarthritis (OA). RESULTS: The lowest SF levels of BPI were found in PsA (145.3 +/- 97.3 ng/ml), significantly lower than in RA (307.7 +/- 42.8 ng/ml, p = 0.0001) and similar to those in OA (151.1 +/- 52.4 ng/ml). Furthermore, only in PsA, and not in the RA and OA subgroups, correlations were observed between BPI and the indices considered, including TNF alpha (r = 0.746, p = 0.0004). CONCLUSION: Due to its relationship with local inflammation, SF BPI may play a role in the pathogenesis of arthropathies, in particular PsA.
11136879 Synovial fluid matrix metalloproteinase-3 levels are increased in inflammatory arthritides 2000 Dec OBJECTIVE: To study the levels of matrix metalloproteinase-3 (MMP-3) in the knee synovial fluid (SF) of inflammatory arthropathies (rheumatoid arthritis whether erosive or not, reactive arthritis, acute crystal arthritis) and degenerative arthropathies [chronic crystal disease, osteoarthritis and (control) meniscus pathology] and to correlate them with the degree of joint destruction, local inflammatory and immune parameters and systemic markers of inflammation. METHODS: SF levels of MMP-3 (precursor, active and tissue inhibitor of MMP-bound forms), tumour necrosis factor (TNF) alpha, soluble TNF receptors I and II, interleukin (IL)-6 and soluble IL-6 receptor were measured by ELISA in 107 inflammatory and 53 degenerative arthropathies. RESULTS: MMP-3 levels in SF were (i) significantly higher in inflammatory than in degenerative arthropathies; (ii) not related to the degree of joint destruction; (iii) significantly correlated with the levels of all SF markers tested and with erythrocyte sedimentation rate and serum levels of C-reactive protein and fibrinogen. CONCLUSION: Increased MMP-3 levels in SF are found in inflammatory arthropathies and are not specific for erosive joint diseases. MMP-3 in SF is therefore a potential candidate for the assessment of the inflammatory process in joints. However, the exclusive determination of the active form could indicate the degree of joint destruction.
10888712 A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment 2000 Jun OBJECTIVE: To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). METHODS: In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group. RESULTS: After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate vs no drug-related deaths among the subjects receiving leflunomide. CONCLUSIONS: Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.
11147769 Combination therapy with hydroxychloroquine, gold sodium thiomalate and methotrexate in ea 2000 During recent years, aggressive therapeutic approaches have been proposed in order to control the Rheumatoid Arthritis (RA) activity and to avoid joint destruction. Here we report the results of an open 3-year trial on the combination of three second-line drugs, hydroxychloroquine (HCQ), methotrexate (MTX) and gold sodium thiomalate (GST), in early active RA. Four men and 17 women were enrolled in the study and were treated during the first year with HCQ 400 mg/day, GST 50 mg/week and oral MTX 7.5 mg/week; during the second and the third years the doses of HCQ and MTX were reduced to 200 mg/day and 5 mg/week, respectively; the interval between the GST injections was progressively increased until 4 weeks. Prednisone at an initial dose not higher than 10 mg/day was associated. Sulindac was allowed. Eight patients left the study because of side-effects, 2 patients abandoned the study, 12 patients compleated the 3 years of treatment. We obtained a significant and early amelioration of both clinical and laboratory parameters during the first year; in the two subsequent years the positive results were maintained. In our opinion the most significant result is the absence of anatomical progression in 10 out of 12 patients, even if a more prolonged observation is necessary to obtain more reliable data.