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ID PMID Title PublicationDate abstract
15494359 A linguistic framework for assessing the quality of written patient information: its use i 2005 Jun Patient information leaflets are an important adjunct to verbal exchange between doctor and patient. Their value is dependent upon whether they contain useful information from the viewpoint of the patient and are easily understood. We developed a framework based upon linguistic theory for assessing the quality of written patient information and applied it to a set of leaflets about methotrexate treatment. Items included the overall structure of the text, the technicality of the vocabulary used, the number of content words per clause ('lexical density'), and the clarity of the role relationship between author and reader. The leaflets consisted of up to nine identifiable sections (range 3-8): background information about the drug, summary of its use, dosage instructions, outline of benefits and side-effects, monitoring information, constraints on patient behavior, storage instructions, and clinical contact availability. Most leaflets contained a high number of content words per clause and the identity of the author was clear in only three (17%). Linguistic analysis provides highly relevant information about written patient information. Together with critical assessment of factual and visual aspects, consideration of key linguistic features should improve the quality of informational texts for our patients.
17114801 Influenza vaccination as model for testing immune modulation induced by anti-TNF and metho 2007 Apr OBJECTIVES: To compare serological response to influenza vaccine in patients with long-standing rheumatoid arthritis (RA) treated with tumour necrosis factor (TNF) blockers and/or methotrexate (MTX) and controls. METHODS: Altogether, 149 patients with RA and 18 healthy subjects were vaccinated. Fifty patients were treated with TNF blockers (etanercept or infliximab) in combination with MTX (TNF blockers + MTX), while 62 patients received TNF blockers alone or with other disease-modifying anti-rheumatic drugs (DMARDs) (TNF blockers without MTX). Thirty-seven patients were treated with MTX without TNF blockers (MTX). Vaccination was performed with trivalent vaccine (Influvax or Vaxigrip) both containing 15 microg haemagglutination inhibition (HI) of each of two A strains (H1N1 and H3N2) and one of B strains (B1 or B2). Serum samples were collected prior to and 4-6 weeks after vaccination and titrated against all four strains using HI assay. A positive immune response was defined as > or =4-fold increase compared with pre-vaccination titre levels. A titre > or =40 was considered protective. Pre- and post-vaccination geometric mean titres (GMT) were compared. RESULTS: Post-vaccination titre levels increased significantly in all groups, also reflected by high frequencies of positive immune responders. A positive immune response to combinations of all strains was significantly better for the MTX group. Individuals with protective levels before vaccination responded less well as a group. CONCLUSIONS: RA patients treated with MTX without TNF blockers had significantly better serological response to influenza vaccination compared with those receiving TNF blockers alone or in combination with MTX and/or other DMARDs. However, the immune response is sufficiently large to warrant influenza vaccination to all RA patients regardless of treatment.
16465653 Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis. 2006 Feb OBJECTIVE: To evaluate safety and efficacy of etanercept treatment in elderly (age > or = 65 yrs) and younger adult subjects (age < 65 yrs) with rheumatoid arthritis (RA). METHODS: Subset analyses were used to describe the safety and efficacy of etanercept in elderly and younger subjects treated for early and disease modifying antirheumatic drug-resistant or late-stage RA (ERA and LRA) in one of 4 randomized controlled clinical studies (N = 1353) or 2 longterm extensions (N = 1049). RESULTS: Rates of serious adverse events tended to be higher in elderly than younger subjects; however, rates of safety events observed in elderly etanercept-treated subjects did not exceed rates in elderly placebo or methotrexate (MTX)-treated subjects. With regard to efficacy measures [American College of Rheumatology 20% response (ACR20), ACR50, and ACR70], elderly subjects tended to have somewhat less robust responses to treatment than younger subjects. However, for both age groups, treatment with etanercept resulted in improved efficacy and function compared with control treatment, and combination therapy with etanercept plus MTX resulted in greater efficacy than either etanercept or MTX used alone. Efficacy responses of elderly subjects were sustained for up to 6 years. Radiographic progression (measured using modified Sharp Score) after one year of treatment was lower in subjects treated with both etanercept and MTX compared with subjects treated with either agent used alone, and this pattern was similar in both age groups. CONCLUSION: Consistent with responses in younger subjects, elderly subjects with RA treated with etanercept experienced significant improvement in disease activity and function without incurring additional safety concerns.
16393444 Real-world effectiveness of select biologic and DMARD monotherapy and combination therapy 2006 Jan OBJECTIVE: To evaluate the effectiveness of select biologics, methotrexate (MTX), and other disease-modifying anti-rheumatic drugs (DMARDs) in the management of adult rheumatoid arthritis (RA) in routine clinical practice. RESEARCH DESIGN AND METHODS: RADIUS (Rheumatoid Arthritis DMARD Intervention and Utilization Study) comprises two prospective, 5-year, observational registries of over 10 000 patients. Over 4600 patients who initiated MTX or a biologic regimen (etanercept [ETN], infliximab [INF], ETN + MTX, and INF + MTX) and who had at least one on-regimen, follow-up evaluation, were included in this analysis. Adalimumab was not included because it had not yet received FDA approval at RADIUS initiation. Other common DMARD regimens (N = 762) were also compared with MTX. Patients who initiated less commonly used regimens, such as anakinra or cyclosporine, and those who did not have at least one on-regimen, follow-up evaluation, were not eligible for this analysis. Because ESR/CRP measurements were often not available, a modified ACR20 response (mACR20), defined as three out of four response criteria excluding ESR/CRP, was used to assess response at 12 months. Logistic regression analysis was performed to control for baseline covariates that may affect outcomes. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients who achieved a mACR20 response at 12 months post-RADIUS entry. RESULTS: After adjusting for baseline covariates, patients receiving either ETN + MTX or ETN monotherapy were more likely to achieve a mACR20 response at 12 months than patients receiving MTX alone (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.09-1.52; p < 0.01 and OR 1.23, 95% CI 1.02-1.47; p < 0.05, respectively). Conversely, patients treated with MTX + leflunomide (LEF) were less likely to achieve a mACR20 response than those receiving MTX alone (OR 0.68, 95% CI 0.48-0.96; p < 0.05). Significant differences were not observed between patients receiving MTX alone and either INF + MTX, MTX + hydroxychloroquine, MTX + hydroxychloroquine + sulfasalazine, INF monotherapy, or LEF monotherapy. CONCLUSION: These data from routine rheumatology clinical practice settings highlight the effectiveness of common biologic and DMARD therapies, and provide additional data beyond those of randomized, controlled trials.
16265690 Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. 2005 Nov OBJECTIVE: To determine the rates of reported non-melanoma skin cancer (NMSC) in a large cohort of patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA) and to determine risk factors for the development of NMSC in patients with RA. METHODS: Self-reported information from 15,789 patients with RA and 3,639 patients with OA were collected through semi-annual questionnaires since 1999. Survival analyses were used to determine incidence rates for NMSC among patients with RA and OA. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HR) for the development of NMSC. Separate analyses were performed for patients with RA to explore associations between use of immunosuppressive medication and development of NMSC. RESULTS: The crude (unadjusted) incidence rate for reported NMSC among patients with RA and OA were 18.1 and 20.4 per 1000 patient years, respectively. OA patients were older, more likely to be Caucasian, and had higher past incidence of NMSC. Age, male sex, Caucasian race, and history of NMSC prior to entry into the database were associated with an increased risk of NMSC in multivariate Cox proportional hazard models. After adjustment for covariates, RA was associated with an increased risk of NMSC (HR 1.19, p = 0.042). Among RA patients, the development of NMSC was associated with use of prednisone (HR 1.28, p = 0.014) and tumor necrosis factor (TNF) inhibitors alone or with concomitant methotrexate (HR 1.24, p = 0.89 and HR 1.97, p = 0.001, respectively) in addition to established risk factors including fair skin, age, male sex, and previous history of NMSC. No association was found between use of methotrexate or leflunomide and development of NMSC (HR 1.12, p = 0.471, HR 0.83, p = 0.173, respectively). CONCLUSION: In this large, national cohort, RA was associated with an increased risk for development of NMSC. Among patients with RA, use of TNF inhibitors and prednisone were associated with an increased risk of NMSC.
16835876 Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat model 2006 Oct Many studies have been carried out in recent years on the pharmacological effects of nigella sativa seeds that have uncovered their antiinflammatory and immunological effects. The objective of this study was to explore the antiinflammatory effects of thymoquinone on arthritis in rat models. Rats with arthritis induced by Freund's incomplete adjuvant were assigned into five groups: group 1: controls 0.9% NaCl (n = 7); group 2: 2.5 mg/kg thymoquinone (n = 7); group 3: 5 mg/kg thymoquinone (n = 7); group 4: Bacilli Chalmette Guerin (BCG) 6 x 10(5) CFU (n = 7); group 5: methotrexate 0.3 mg/kg (n = 7). Signs of inflammation on the claw and radiological signs were searched for and TNF-alpha and IL-1beta were measured. The results of control and other groups were compared. As a result, thymoquinone, confirmed clinically and radiologically, suppressed adjuvant-induced arthritis in rats.
17182267 Long-term results of infliximab therapy in rheumatoid arthritis: experience acquired by th 2007 Jan OBJECTIVE: Infliximab is effective in patients with rheumatoid arthritis (RA). Add-on infliximab therapy in patients on methotrexate results in a rapid gain in effectiveness, which lasts at least 1 year. The objective of this study was to evaluate the effectiveness and continuation rate of infliximab in patients with RA after the first year of treatment. METHODS: The first 50 patients with RA who were given infliximab in the North-Pas-de-Calais region of France were included in a multicenter open-label study. The patients had severe RA or failed to respond to conventional medications. Infliximab was given in a dosage of 3 mg/kg every 8 weeks in combination with methotrexate. Effectiveness was evaluated using the DAS28-3 score and EULAR response criteria. The dates and reasons of infliximab discontinuations were recorded. RESULTS: The 2-year infliximab continuation rate was 70%. Serious adverse events requiring infliximab discontinuation occurred in 7 patients. Mean DAS28-3 scores in the 35 patients who took infliximab for at least 2 years were 6.42 at baseline, 4.33 after 30 weeks, 4.31 after 54 weeks, and 3.86 after 102 weeks. According to EULAR criteria after 102 weeks, there were 12 good responders, 18 moderate responders, and 5 nonresponders. CONCLUSION: Experience acquired in the North-Pas-de-Calais district of France suggests that infliximab is continued for more than 2 years in more than two-thirds of patients and remains effective over this period.
16393443 Real-world utilization of DMARDs and biologics in rheumatoid arthritis: the RADIUS (Rheuma 2006 Jan OBJECTIVE: Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice. RESEARCH DESIGN AND METHODS: Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5-year study. RESULTS: RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy. CONCLUSIONS: These real-world data provide evidence of the prescribing practices of rheumatologists in 2001-2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making.
15709988 Oral methotrexate in ulcerative colitis. 2005 Feb 15 BACKGROUND: We performed an audit of methotrexate for ulcerative colitis, because efficacy is unclear. Aim : To investigate the role of methotrexate in the management of ulcerative colitis. METHODS: Patients with ulcerative colitis treated with oral methotrexate at the inflammatory bowel disease clinics of Oxford and Wycombe General Hospital, UK, were evaluated. Efficacy was defined by remission (complete steroid withdrawal for >3 months) and response (good, partial or nil, proportionate reduction of steroids). RESULTS: There were 50 patients (42 ulcerative colitis alone; eight had rheumatoid arthritis associated with ulcerative colitis and were analysed separately). Indications for methotrexate in ulcerative colitis alone were azathioprine intolerance (31 of 42) and lack of benefit from azathioprine (11 of 42). The mean dose of methotrexate in ulcerative colitis alone was 19.9 mg/week for a median of 30 weeks (range: 7-395). Remission occurred in 42%. The response was good in 54% and partial in 18%. Side-effects occurred in 23%; 10% stopped treatment because of side-effects. Of those treated with methotrexate because of treatment failure with azathioprine, three of 11 achieved remission, but four came to colectomy within 90 days of starting methotrexate. The colitis remained in remission in seven of eight of those with RA treated with methotrexate and ulcerative colitis (mean dose 15.0 mg/week). CONCLUSION: Oral methotrexate (approximately 20 mg/week) is well-tolerated and moderately effective in steroid-dependent or steroid-refractory patients with ulcerative colitis.
16190361 [Aberrant over-expression of adenosine deaminase and its significance on rheumatoid arthri 2005 Aug Adenosine deaminase (ADA; EC 3.5.4.4) activity is elevated in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Since the anti-inflammatory effect of methotrexate is reportedly associated with increased levels of extracellular adenosine, the study was undertaken to clarify the role of two ADA isozymes (ADA1 and ADA2) in the pathogenesis of RA. The activities of ADA1 and ADA2 were measured in SF from RA and osteoarthritis (OA) patients, sera from RA patients, and lysates prepared from mononuclear and polymorphonuclear cells from RA-SF, peripheral blood from RA patients, and fibroblast-like synoviocytes (FLS) from RA and OA patients. Also investigated were the effects of proinflammatory cytokines on ADA1 activity and ADA mRNA expression in RA-FLS by the real-time PCR assay. The adenosine concentration in RA-SF was determined using a radioimmunoassay. The adenosine concentration in RA-SF ranged from 0.027 microM to 0.508 microM (mean+/-SD, 0.156+/-0.132). At these concentrations, ADA1 is expected to be functionally dominant due to its higher affinity for adenosine. ADA1 activity in RA-SF (14.4+/- 8.5 IU/l) was significantly higher than in OA-SF(3.0+/- 1.1 IU/l) or RA-sera (3.0+/-0.6 IU/l), suggesting they are the major source of ADA1 in RA-SF. Proinflammatory cytokines failed to affect ADA1 activity or ADA mRNA expression in RA-FLS. Taken together, these findings suggest that the elevated ADA1 activity is an intrinsic characteristic of RA-FLS, which likely contributes to the pathogenesis of RA by neutralizing the anti-rheumatic properties of endogenous adenosine.
16120053 Abatacept: a costimulatory inhibitor for treatment of rheumatoid arthritis. 2005 Sep T cell costimulation is believed to be crucial in orchestrating immune responses that lead to inflammation and destruction in rheumatoid arthritis (RA). Abatacept is a novel recombinant CTLA4Ig fusion protein that selectively modulates costimulation via interrupting the CD28:CD80/86 pathway, resulting in downregulation of T cell activation and multiple ensuing effector mechanisms. Abatacept has been shown to be efficacious, either when given alone or in combination with methotrexate, in patients with active RA, including anti-TNF failures. Improvements in clinical signs and symptoms, slowing of radiological progression, and enhancement in patient function and pain have been reported in clinical trials. Infusions were well-tolerated with a favourable safety profile similar to placebo and no appreciable immunogenicity. Abatacept is the first in a new class of biological response modifiers called costimulatory blockers.
14628151 The effect of low-dose prednisone on bone mineral density in Peruvian rheumatoid arthritis 2005 Mar OBJECTIVE: The aim of this study was to determine the difference between bone mineral density (BMD) of rheumatoid arthritis (RA) patients on low-dose prednisone and matched RA patients without prior systemic corticosteroid therapy. METHODS: Ninety patients attending our clinics and receiving 10 mg/day of prednisone or less for at least the previous 3 consecutive months were studied. The control group comprised 90 selected RA patients without corticosteroid therapy matched for age, race, gender, disease duration, use of methotrexate, postmenopause, and Health Assessment Questionnaire score. The BMD was measured using dual X-ray absorptiometry. RESULTS: Patients on prednisone had lower BMD than controls (0.94 +/- 0.17 vs 0.96 +/- 0.17 for L2-4 and 0.73 +/- 0.14 vs 0.76 +/- 0.16 for femoral neck), but these differences were not statistically significant (P > 0.05). In post hoc analysis, postmenopausal women on prednisone had more bone loss in femoral neck than controls (0.68 +/- 0.13 vs 0.74 +/- 0.15). CONCLUSION: Bone mineral density was not significantly reduced by low-dose prednisone in this diverse group of RA patients. A reduction in hip BMD was seen in postmenopausal women on prednisone.
15769913 Clinical efficacy of infliximab plus methotrexate in DMARD naive and DMARD refractory rheu 2005 Apr BACKGROUND: Tumour necrosis alpha (TNF alpha) blocking agents lead to pronounced clinical effects and reduced synovial infiltrate in rheumatoid arthritis. Laboratory and clinical studies suggest that TNF alpha independent pathways play a role in the disease. OBJECTIVES: To evaluate the immunopathological effects of combination therapy on rheumatoid synovial tissue in order to identify TNF alpha independent mechanisms. METHODS: 12 rheumatoid patients, including four DMARD (disease modifying antirheumatic drug) naive patients with early disease, were studied for the effect of combination therapy with infliximab and methotrexate on the synovial infiltrate. Biopsies and clinical assessments (DAS28) were carried out before the first and after the third infusion of infliximab. Synovial inflammation was scored semiquantitatively. Co-expression of CD38(+) cells was studied by an immunofluorescent double labelling technique. RESULTS: Marked clinical responses were associated with a global reduction in the synovial infiltrate and expression of cytokines, notably interleukin 18 and TNF alpha, but low grade disease activity persisted. There was no effect on the expression of CXC chemokine ligand (CXCL12), and germinal centre-like structures were still detectable in synovial tissue in two patients after treatment. CD38(+) activated T cells were more resistant to treatment than CD38(+) plasma cells. No differences in clinical response or effects on synovial infiltrate were observed between DMARD refractory and DMARD naive patients. CONCLUSIONS: Persistent expression of CXCL12 and incomplete resolution of lymphocytic infiltrates after infliximab plus methotrexate indicates that TNF alpha independent mechanisms are operative in rheumatoid arthritis. This may contribute to low grade disease activity, even in DMARD naive patients with early disease.
16899502 Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis patients are u 2007 Mar OBJECTIVES: To identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (RA) patients' responses to infliximab. METHODS: A total of 76 patients with active RA (American College of Rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. At week 14, infliximab efficacy was evaluated using disease activity score (DAS)28. A serum sample, collected just before starting infliximab, was tested by ELISA (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment, glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: C-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-kappaB ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical clustering was performed with The Institute for Genomic Research (TIGR) multiple experiment viewer software. RESULTS: Good, moderate and non-responder rates were 6.5, 61.8 and 31.5%, respectively. No significant difference was observed between responders and non-responders, regardless of the serum parameters considered. Analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab. CONCLUSION: The search for soluble markers in RA patients' sera likely to predict response to infliximab because of their involvement in RA pathogenesis seems disappointing. However, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis.
17021714 Adenosine and cytokine levels following treatment of rheumatoid arthritis with dipyridamol 2006 Nov Adenosine can suppress the release of tumour necrosis factor-alpha (TNF-alpha) from activated monocytes and macrophages, and may contribute to the anti-inflammatory activities of methotrexate and sulphasalazine. Dipyridamole inhibits the cellular uptake and metabolism of adenosine and we have, therefore, examined the effects of dipyridamole in patients with rheumatoid arthritis in an attempt to alleviate their symptoms. Forty patients aged 18-75 years were randomised to receive dipyridamole 400 mg/day or placebo. Blood samples were taken at baseline and at monthly intervals for 6 months. Purines were determined by HPLC and cytokines by ELISA. After 3 months of treatment there were significant reductions in neopterin levels and in the modified Health Assessment Questionnaire score, but these were not maintained. Dipyridamole had no effect on disease severity or the levels of purine metabolites, interleukin-1beta (IL-1beta), IL-6, TNF-alpha, lipid peroxidation products, erythrocyte sedimentation rate or C-reactive protein. In conclusion, rheumatoid arthritis patients showed no clinical improvement following treatment with dipyridamole for 6 months.
16646989 Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid ar 2006 We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 +/- 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients.
15990992 The inhibitory effect of disease-modifying anti-rheumatic drugs and steroids on gliostatin 2005 Oct Gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) is known to have both angiogenic and arthritogenic activities. The purpose of this study was to investigate whether disease-modifying anti-rheumatic drugs (DMARDs) and steroids are involved in the regulation of GLS expression. Fibroblast-like synoviocytes (FLSs) obtained from patients with rheumatoid arthritis (RA) were cultured and stimulated by interleukin (IL)-1beta with or without DMARDs and steroids. The expression levels of GLS were determined using the reverse transcription-polymerase chain reaction and an ELISA. In cultured rheumatoid FLSs, the expression of GLS mRNA was significantly increased by stimulation with IL-1beta. By contrast, GLS mRNA levels in IL-1beta-stimulated FLSs were reduced by treatment with aurothioglucose (AuTG) and dexamethasone (DEX). These findings indicate that AuTG and DEX have anti-rheumatic activity, which is mediated via the suppression of GLS production. Neither methotrexate (MTX) nor sulfasalazine (SSZ) had a significant influence on GLS levels in our study.
16370218 [Septic oligoarthritis as a complication of rhumatoid arthritis--a case report]. 2005 Oct We present the case a 53-year-old patient followed-up since 1999, for erosive AR treated with methotrexate and glucocorticoids. In April 2000, he had an arthritis of the right knee. The identification of an enterobacter in blood culture, and synovial biopsy results permitted the diagnosis of septic arthritis. After 23 days of antibioterapy treatment, the patient had an arthritis of the left knee. The infectious origin was confirmed by synovial biopsy. The course was better after adaptation of the antibiotics. Septic arthritis is then a serious complication of AR. It requires a fast and multidisciplinary management. It can be threatenig in fragile and immunocompromised patients. The functional prognosis is especially compromised in polyarticular septic arthritis.
16088130 Reduction of temporomandibular joint pain after treatment with a combination of methotrexa 2005 The aims were to investigate the effect of intravenous infusions of the tumor necrosis factor-alpha (TNF-alpha) antibody infliximab on symptoms and signs of temporomandibular joint (TMJ) involvement in relation to effects on synovial fluid and plasma proinflammatory TNF-alpha, interleukin-1beta (IL-1beta) and interleukin-6 as well as antiinflam matory soluble TNF receptor II (TNF-sRII), interleukin-1 receptor antagonist (IL-1ra), soluble IL-1 receptor II (IL-1sRII) and interleukin-10 (IL-10) in patients with active rheumatoid arthritis (RA). Nineteen patients with TMJ involvement taking methotrexate were included in the study. TMJ and general joint pain intensity as well as pain on mandibular movements, tenderness to digital palpation, pressure pain threshold and maximum mouth-opening capacity were assessed in a clinical examination. The effect of infliximab was assessed after 2 and 14 or 22 weeks. TMJ synovial fluid and venous blood were collected for cytokine analysis at all occasions while determination of erythrocyte sedimentation rate and C-reactive protein were performed at baseline and at long-term follow-up only. Reduction of TMJ pain was associated with raised levels of synovial fluid TNF-sRII and IL-1sRII as well as raised plasma levels of IL-1ra and IL-10. Decreased erythrocyte sedimentation rate was associated with decreased tenderness to digital palpation. Reduced general joint pain intensity was associated with reduced plasma levels of IL-6 and C-reactive protein. In conclusion, systemic treatment with a combination of infliximab and methotrexate reduces TMJ pain in RA in association with an increase in anti-inflammatory cytokines and receptors in synovial fluid and plasma.
16870092 Treatment continuation rate in relation to efficacy and toxicity in long-term therapy with 2006 May OBJECTIVE: To evaluate the effectiveness of disease-modifying antirheumatic drugs, namely, methotrexate (MTX), sulfasalazine (SSZ) and bucillamine (BUC) at low-doses (4, 6 or 8 mg MTX, 500 or 1,000 mg SSZ, and 100 or 200 mg BUC) in 1,358 patients with a follow-up of at least 12 months and more than 120 months. METHODS: Clinical assessments were based on the number of painful joints (NPJ) and that of swollen joints (NSJ), CRP level, erythrocyte sedimentation rate, rheumatoid factor level and morning stiffness before and after treatment. Results were evaluated on the basis of the duration of treatment for each drug with inefficacy or inadequate efficacy as one endpoint for discontinuation and adverse drug reactions (ADRs) as the other in single agent and combination therapy. The incidence and nature of ADRs in single and combination treatment are described. RESULTS: The effects of MTX, SSZ and BUC on clinical parameters were monitored over the first three months, and in particular, NPJs and NSJs were found to decrease significantly during single agent MTX or BUC treatment over 108 months. CRP levels remained significantly improved for more than 120 months with MTX. In the single and combination long-term treatments, continuation rate with inefficacy or inadequate efficacy as the end point achieved for each of the treatments were 83.1% for MTX, 76.0% for BUC, 68.5% for SSZ, and in the case of the combination treatments, these rates were 83.3% for MTX + BUC and 71.0% for MTX+SSZ. Continuation rates using ADRs as the end point were 88% for SSZ, 79.6% for BUC and 79.4% for MTX. The incidences of ADRs for the various treatments were: MTX 22.2%, SSZ 11.0%, BUC 20.6%, MTX + BUC 30.0% and MTX + SSZ 31.2%. CONCLUSION: MTX showed the highest efficacy even though it was administrated at a low dose (6-8 mg), as a single agent or in combination with other treatment. However, in combination treatments, the continuous duration of treatment ending in ADRs as the end point were lower than those in single treatments with MTX, SSZ and BUC.