Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 12390945 | Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with | 2002 Oct 22 | BACKGROUND: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-alpha in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-alpha antibody infliximab on disease activity and endothelial function in patients with active RA. METHODS AND RESULTS: Eleven RA patients (mean age 46+/-5 years; disease duration 9+/-2 years) with high disease activity despite treatment with stable doses of methotrexate ( | |
| 15361374 | Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following a | 2004 Oct | OBJECTIVE: To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) in patients with rheumatoid arthritis. METHODS: 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs (DMARD) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks, and subsequently bimonthly, in combination with methotrexate. Serum samples were collected at baseline and at week 24. A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies; RF were detected using a quantitative nephelometric assay. RESULTS: At baseline, 38 of the 43 patients (88%) were positive for anti-CCP antibodies, and 41 (95%) were positive for RF. The serum titre of anti-CCP and RF decreased significantly after six months of treatment (p = 0.0001 and p<0.0001, respectively). When the patients were grouped on the basis of their clinical response to infliximab, a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement (ACR 20 and ACR 50). CONCLUSIONS: Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement, suggesting that these measurements may be a useful adjunct in assessing treatment efficacy. | |
| 15115713 | Differential effects of leflunomide and methotrexate on cytokine production in rheumatoid | 2004 Sep | BACKGROUND: T cells have a pivotal role in RA. Leflunomide inhibits pyrimidine biosynthesis, to which T cells are especially susceptible, and therefore may have a different cytokine profile than methotrexate. MATERIALS AND METHODS: Serum samples of 100 patients with RA, treated with leflunomide (n = 50) or methotrexate (n = 50), were collected at baseline, after 16 weeks and after 1 year's treatment. Serum levels of interleukin 6 (IL6), and interferon (IFN) gamma were determined by ELISA. Additionally, peripheral blood mononuclear cells (PBMC) of five healthy volunteers and three patients with RA were isolated and the effects of the active metabolite of leflunomide (A77-1726, 0-200 mmol/l) on cell proliferation and on IL6 and IFNgamma production were determined by ELISA. In peripheral blood lymphocytes (PBL) and monocytes (PBM) from two healthy volunteers the effects of A77-1726 on IL6 production were measured by ELISA and PCR. RESULTS: Mean (SEM) serum levels of IFNgamma were significantly reduced after leflunomide treatment (baseline 43 (10) pg/ml; 1 year 29 (7) (p = 0.015), but there was no change in IL6 levels (baseline 158 (41), 1 year 151 (48)). Both IFNgamma and IL6 levels were significantly reduced after methotrexate treatment. This observation was supported by in vitro experiments. The production of IFNgamma by PBL was inhibited by A77-1726, but IL6 production by PBM was not inhibited. CONCLUSION: The differential effect on IFNgamma and IL6 production supports the hypothesis that activated T cells are preferentially inhibited by leflunomide. An explanation may be either inhibition of uridine synthesis or effects on signal transduction pathways. | |
| 12219317 | Vasculitis secondary to staphylococcal Protein A immunoadsorption (Prosorba column) treatm | 2002 Aug | OBJECTIVE: Vasculitis is a rare complication of immunoadsorption treatment with staphylococcal Protein A (Prosorba column). The prevalence, clinical characteristics, pathophysiology, treatment, and outcome of vasculitis secondary to immunoadsorption treatment is not known. METHODS: The authors describe a 57-year-old woman with rheumatoid arthritis (RA) resistant to methotrexate and etanercept, who developed severe leukocytoclastic vasculitis after the 9th weekly treatment with Prosorba column. She developed rapidly progressive crescentic glomerulonephritis and required treatment with cyclophosphamide and high-dose prednisone. Subsequently, renal function stabilized and RA remitted. Through the literature search and by reviewing information submitted to Cypress Biosciences Inc (manufacturer of Prosorba columns), available world literature on vasculitis secondary to Prosorba column treatment was compiled. RESULTS: Immune complex deposition of staphylococcal Protein A (SPA)/SPA antibodies in the glomeruli precipitated the renal disease in our patient. Twenty cases of vasculitis (calculated prevalence, 1 per 400), 5 with internal organ involvement, have been reported in patients treated with Prosorba column for thrombocytopenic purpura. Seven RA patients treated with Prosorba column developed vasculitis (prevalence, 7 per 400), 3 with internal organ involvement. CONCLUSIONS: Vasculitis secondary to staphylococcal Protein A immunoadsorption therapy occurs rarely and appears to be related to development of SPA/SPA antibody immune complexes. Rheumatologists should be aware of this potentially serious complication of the Prosorba column treatment for RA. | |
| 15228844 | Efficacy of cyclosporin-A in refractory rheumatoid arthritis. | 2004 Mar | OBJECTIVE: The aim of the study was to evaluate the efficacy of cyclosporin-A in patients of rheumatoid arthritis not responding to standard therapy early in the course of the disease. DESIGN: A non-randomized controlled clinical trial. PLACE AND DURATION OF STUDY: Outpatients Department of Abbasi Shaheed Hospital and Imam Clinic over a period of 18 months from March 1999 through September 2000. MATERIALS AND METHODS: The study was carried out on 63 patients of both gender suffering with refractory rheumatoid arthritis for at least 3 months. Patients were divided into two groups A and B. Group-A was the experimental one, treated with cyclosporin-A in combination with methotrexate while Group-B was continued with methotrexate alone. Their pre and post assessments regarding recovery criteria and drug profile had been done in order to establish the efficacy of cyclosporin-A. RESULTS: The study showed a significant difference (p<.000 with a.05) after six months between treatment group and the controls, in the mean values of articular index (2.53 vs. 5.39), right grip (14.28 vs. 33.8 mmHg ), left grip strengths (16.5 vs. 34.31 mmHg) and number of tender joints (26.9% vs. 38.6%). Furthermore, a significant negative correlation between articular index at recruitment and visual analogue scale (VAS) of pain after 6 months of therapy was observed in experimental group. CONCLUSION: This study indicates that the combination of cyclosporin with methotrexate benefits rheumatoid arthritis patients refractory to methotrexate monotherapy. Cyclosporin was well tolerated by those having shorter duration of disease. | |
| 11915973 | Health-related quality of life in early rheumatoid arthritis: impact of disease and treatm | 2002 Mar | OBJECTIVE: To document the burden of early rheumatoid arthritis (RA) on health-related quality of life (HQL) and compare changes in HQL across 2 treatments. STUDY DESIGN: Analysis of HQL scores among patients enrolled in a multicenter, double-blind, randomized control trial of early RA treatment. PATIENTS AND METHODS: A total of 424 patients with early RA were randomized to 1 of 2 treatment groups: etanercept or methotrexate. Patients were treated and followed for 52 weeks. Health-related quality of life was assessed before and throughout treatment using the Medical Outcomes Study Short Form 36 Health Survey (SF-36) and the Health Assessment Questionnaire (HAQ). The HQL burden of RA was established by comparing SF-36 scale scores to general US population norms. The impact of treatment on HQL was determined by comparing scores on both SF-36 and HAQ scales. RESULTS: Before treatment, RA patients showed significant decrements in scores on all SF-36 scales and summary measures in comparison with age- and sex-matched general US population norms, multivariate analysis of variance (MANOVA) F(8,2815) = 204.6, P < .0001. After 52 weeks of treatment, 7 of 8 SF-36 scales and the physical summary measure remained significantly below the general US population norm, MANOVA F(8,2815) = 41.9, P < .0001. Patients randomized to etanercept showed significantly better HQL improvement earlier in treatment than patients randomized to methotrexate on the SF-36 physical summary, MANOVA F(10,4230) = 6.1, P< .0001, the SF-36 arthritis-specific health index, MANOVA F(10,4230) = 8.5, P < .0001, and the HAQ, MANOVA F(10,4230) = 14.7, P < .0001. At 52 weeks, there were no significant differences between treatment groups. CONCLUSIONS: Rheumatoid arthritis places tremendous disease burden on patients' HQL. Successful treatment of early RA improved HQL. Etanercept showed a rapid HQL response. | |
| 12658918 | [Effect of bizhongxiao decoction on the expression of VEGF in the synovial membrane of C I | 2002 Dec 28 | OBJECTIVE: To observe the effect of bizhongxiao (BZX) decoction on the expression of VEGF in the synovial membrane of C II-induced arthritis(CIA) in rats and to explore the mechanism of BZX decoction in the treatment of rheumatoid arthritis RA. METHODS: Seventy-five SD rats were randomly divided into four groups. The rat experimental arthritis model was established by subcutaneous injection of II collogen. The expression of VEGF was detected with immunohistochemistry in different times. RESULTS: The incidence of arthritis in the rats immunized with C II was approximately 88.57%. The arthritis index of the model group was rising, but that of the BZX decoction group and the methotrexate (MTX) group were decreasing on the 30th day. No expression of VEGF was found in the synovial membrane of the normal group. The expression of VEGF of the model group was notably higher than that of the BZX decoction group and the MTX group in different times (P < 0.01). The expression of VEGF of the model group rose step by step, but that of the BZX decoction group and the MTX group decreased and was significantly lower than that of the model group (P < 0.01). The expression of VEGF of the BZX decoction group was significantly lower than that of the MTX group(P < 0.05). CONCLUSION: The expression of VEGF is relative to the synovial pannus formation in RA. BZX decoction and MTX could decrease the expression of VEGF, but the curative effect of BZX decoction is significantly better than that of MTX. BZX decoction could inhibit the formation of the synovial pannus or bone in RA by decreasing the expression of VEGF. | |
| 15308515 | A randomised comparative study of the short term clinical and biological effects of intrav | 2004 Sep | OBJECTIVES: To compare the short term clinical and biological effects of intravenous (i.v.) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. METHODS: Patients with active RA despite MTX treatment were randomly allocated to receive a single i.v. infusion of MP (1 g) or three i.v. infusions of IFX (3 mg/kg) on weeks 0, 2, and 6. Patients were "blindly" evaluated for disease activity measures. Quality of life (QoL) was evaluated through the SF-36 health survey. Serum matrix metalloproteinase-3 (MMP-3) titres were measured at baseline, weeks 2 and 6. RESULTS: Compared with baseline, significant improvement was noted in all activity measures, including serum C reactive protein (CRP) titres, in the IFX group only. At week 14, 6/9 (67%) and 4/9 (44%) IFX patients met the ACR20 and 50 response criteria, while this was the case in only 1/12 (8%) and 0/12 (0%) MP patients, respectively (p<0.05). None of the QoL scales improved with MP treatment, whereas some did so in the IFX group. Serum MMP-3 titres significantly decreased (41% drop) at week 6 in the IFX group, while no changes were seen in patients given MP. CONCLUSION: This short term randomised comparative study demonstrates that TNF blockade is better than MP pulse therapy in a subset of patients with severe refractory RA, with improvement in not only clinical parameters of disease activity but also biological inflammatory indices, such as serum CRP and MMP-3 titres. | |
| 15166003 | Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is modulated by i | 2005 Feb | OBJECTIVES: To analyse the effect of infliximab on IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies, and determine whether baseline autoantibody titres (IgM RF and anti-CCP antibodies) are associated with changes in acute phase reactants. PATIENTS AND METHODS: 62 patients with refractory RA were treated with infliximab combined with methotrexate. At baseline and week 30, serum samples were tested for IgM RF by two agglutination assays, and for anti-CCP antibodies by an ELISA. Percentage change in C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was calculated. RESULTS: At baseline and week 30 RF titres were reduced significantly during infliximab treatment (p<0.001 and p = 0.038, respectively), whereas anti-CCP antibodies were unchanged (p = 0.240). Baseline IgM RF titres, but not anti-CCP antibodies, correlated inversely with changes in CRP and ESR during treatment. Patients with a marked decrease in acute phase reactants had lower IgM RF titres than those with a smaller decrease in CRP and ESR; no significant differences were found for anti-CCP antibodies. CONCLUSION: The differential effect of infliximab treatment on IgM RF and anti-CCP antibodies, and the different predictive value on changes in acute phase reactants during infliximab treatment support the existing evidence that RF and anti-CCP antibodies are independent autoantibody systems in RA. | |
| 12154207 | The effects of disease-modifying anti-rheumatic drugs on the Health Assessment Questionnai | 2002 Aug | OBJECTIVE: A primary therapeutic goal in rheumatoid arthritis (RA) is to reduce functional disability. The recent introduction of several new drugs for RA creates a need for readily assessing the effectiveness of therapy. Because the consistent use of disease-modifying anti-rheumatic drugs (DMARDs) reduces long-term disability, we analysed the large database of 1817 RA patients from leflunomide trials to assess if changes in the Health Assessment Questionnaire (HAQ) can measure the effectiveness of RA therapy. METHODS: Data from three randomized double-blind RA trials were evaluated. The patients had received 100 mg leflunomide (then 20 mg/day in 807 cases), methotrexate (15-20 mg/day in 669 cases), sulphasalazine (2 g/day in 132 cases) and placebo (in 209 cases). HAQ scores and outcomes were assessed using the American College of Rheumatology core data set. Detailed statistical analyses were made of changes in outcome variables at 1 and 6 months, changes in HAQ scores at 1-12 months, and effect sizes for outcome variables at 6 and 12 months. Multiple regression models of changes in HAQ scores were evaluated using backwards stepwise linear regression. RESULTS: Mean HAQ scores declined progressively with treatment with all three DMARDs. Changes occurred rapidly, and at month 1 were most pronounced with leflunomide. HAQ scores correlated closely with clinical response, as seen in changes in non-responders and ACR 20% and 50% responders. Regression analysis indicated that pain intensity and global assessments were significant determinants of HAQ. CONCLUSION: HAQ scores are sensitive measures of effective DMARD therapy. HAQ may be especially useful early in the treatment process to assess patients' responses to DMARDs that show rapid onset of action, such as leflunomide. | |
| 12117681 | Serum interleukin 18 and interleukin 18 binding protein in rheumatoid arthritis. | 2002 Aug | OBJECTIVE: To measure serum interleukin 18 (IL18) and IL18 binding protein (IL18BP) levels in patients with inflammatory arthropathies, and to identify associations with disease status and the response to treatment. METHODS: Serum samples were obtained before and after methotrexate treatment from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) attending an early arthritis clinic. IL18 and IL18BP were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Sixty patients with RA and 13 with PsA were evaluated. Serum IL18 levels were significantly higher in RA than in PsA (p<0.001). After six months' treatment with methotrexate, IL18 levels were reduced, but the differences were not significant (p=0.052). In cross sectional analyses, no correlations between IL18 levels and measures of disease activity or structural damage in RA were found. In longitudinal analyses, no correlations between IL18 levels and the response to treatment or the degree of progressive joint damage were found. Similarly, IL18BP levels were raised in RA, and were not associated with measures of the clinical status or the response to treatment. CONCLUSION: Raised serum levels of IL18 are consistent with a pathophysiological role in RA. However, in this study measurement of circulating IL18 and IL18BP did not correlate significantly with clinical measures of disease activity or the response to treatment in patients with early RA. | |
| 11934961 | Investigation of the chronic pulmonary effects of low-dose oral methotrexate in patients w | 2002 Mar | OBJECTIVE: Methotrexate has a well-recognized side-effect of acute hypersensitivity pneumonitis. There is concern about whether chronic pulmonary toxicity can occur with methotrexate treatment. Our objective was to compare chest high-resolution computed tomography (HRCT) findings and serial pulmonary function tests in rheumatoid arthritis (RA) patients on methotrexate with findings for a control group of patients with RA who were not being treated with methotrexate. METHODS: Study patients had an initial chest radiograph, full pulmonary function tests and chest HRCT. Pulmonary function tests were then performed regularly over a 2-yr period. RESULTS: Fifty-five RA patients on methotrexate and 73 control patients with RA were enrolled for the study. Mean dose of methotrexate was 10.7 mg/week (S.D. 2.5 mg/week) and mean duration of treatment at entry into the study was 30 (20) months. Twenty per cent of patients with RA treated with methotrexate had pulmonary fibrosis (PF) on initial HRCT compared with 23% in the control group. When the patients with and without PF were compared, there was no statistical difference in the duration (mean difference -4.18 months, P=0.237) or dose (mean difference -0.8 mg/week P=0.52) of methotrexate therapy. Mean changes after 2 yr in forced expiratory volume, forced vital capacity, diffusion capacity for carbon monoxide and residual volumes were not different in the methotrexate group compared with the control group. CONCLUSION: There is no evidence to suggest clinically, from HRCT assessment or serial pulmonary function tests, that low-dose methotrexate is associated with chronic interstitial lung disease. | |
| 11850995 | [Infliximab in aggressive and refractory rheumatoid arthritis. A pilot study]. | 2002 Jan | Rheumatoid arthritis is a chronic inflammatory disease with a progressive course, that frequently provokes permanent incapacity if not adequately treated. Rheumatoid arthritis may be not responsive to the common second line drugs. This study was aimed to treat 15 patients affected by severe refractory rheumatoid arthritis with infliximab. PATIENTS AND METHODS: Fifteen patients with refractory rheumatoid arthritis were treated with infliximab--monoclonal antibody direct to TNF alpha--in association with methotrexate or azathioprine. Infliximab was administered at the dosage of 3 mg/Kg at the weeks 0, 2 and 6 and then every 8 weeks. RESULTS: About half patients ameliorated in agreement with both ACR 20 criteria and DAS28 evaluation. The clinical improvement was accompanied by a reduction of the steroid daily dosage. No relevant side effects were observed. CONCLUSION: Infliximab is effective in a significant number of patients with severe rheumatoid arthritis, with a good tolerability. | |
| 12777636 | Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patie | 2003 Oct | OBJECTIVES: To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. METHODS: Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients. Cultures were stimulated with either bacterial products such as lipo-oligosaccharide (LOS) or Staphylococcus aureus Cowan I (SAC) to activate monocytes or with monoclonal antibodies to CD3 and CD28 to induce polyclonal T-cell activation. We analysed the effect of methotrexate on cytokine production in these systems. RESULTS: We showed that methotrexate inhibits production of cytokines induced by T-cell activation. Among the cytokines inhibited were interleukin 4 (IL-4), IL-13, IFN gamma, tumour necrosis factor-alpha (TNF alpha) and granulocyte-macrophage colony-stimulating factor. Inhibition was seen at concentrations easily achieved in plasma of RA patients taking the drug. IL-8 production was hardly influenced by methotrexate. Furthermore, inhibition was dependent on the stimulus; IL-6, IL-8, IL-1 beta and TNF alpha production induced by LOS or SAC was only slightly decreased by methotrexate. The addition of folinic acid or thymidine and hypoxanthine reversed the inhibitory effects of methotrexate on cytokine production. Concentrations of methotrexate required for inhibition varied between donors. Oral intake of 10 mg methotrexate by RA patients led to marked inhibition of cytokine production in blood drawn after 2 h. CONCLUSIONS: Methotrexate turns out to be an efficient inhibitor of cytokine production induced by T-cell activation in freshly drawn blood. This is due to inhibition of the de novo synthesis of purines and pyrimidines. Cytokines produced by monocytes are hardly affected by methotrexate. | |
| 12571839 | Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor | 2003 Feb | OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) has been implicated in the pathogenesis of certain inflammatory diseases. Two TNFalpha-neutralizing agents are licensed in the US. Infliximab is licensed for the treatment of Crohn's disease (CD) and, when used with methotrexate, for the treatment of rheumatoid arthritis (RA). Etanercept is licensed for the treatment of RA, including juvenile RA, and, more recently, was licensed for the treatment of psoriatic arthritis. Because of the potential for decreased host resistance to infectious agents due to treatment with anti-TNFalpha agents, we sought to evaluate postlicensure cases of opportunistic infection, including Listeria monocytogenes, in patients treated with these products. METHODS: The FDA Adverse Event Reporting System, a passive monitoring system, was reviewed to identify all reports of adverse events (through December 2001) associated with L monocytogenes infection in patients treated with infliximab or etanercept. RESULTS: Fifteen cases of L monocytogenes infection associated with infliximab or etanercept treatment were identified. In 14 of these cases, patients had received infliximab. The median age of all patients was 69.5 years (range 17-80 years); 53% were female. Six deaths were reported. Among patients for whom an indication for use was reported, there were 9 patients (64%) with RA and 5 patients (36%) with CD (information was not reported for 1 patient). All patients for whom information was reported were receiving concurrent immunosuppressant drugs. CONCLUSION: Postlicensure surveillance suggests that L monocytogenes infection may be a serious complication of treatment with TNFalpha-neutralizing agents, particularly infliximab. | |
| 12215867 | Effect of methotrexate on pulmonary function in patients with rheumatoid arthritis--a pros | 2002 Sep | If given in high doses, methotrexate (MTX), a folate antagonist, could cause pulmonary complications. To evaluate the pulmonary effects of low-dose methotrexate, 55 newly diagnosed patients with rheumatoid arthritis (RA) prescribed with MTX were studied prospectively. A significant reduction in percent predicted values of forced expiratory volume (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), and functional residual capacity (FRC) was observed after 2 years of MTX treatment. A significant increase in the FEV(1):FVC ratio was also observed. In comparison to the normal annual decline in healthy adults, the actual reduction in observed values in the patients was significantly greater (3.2, 6.3, and 6.7 times normal for FEV(1), FVC, and TLC, respectively). PaO(2) and oxygen saturation showed marginal but significant improvement. It was concluded that low-dose MTX treatment in RA might cause an accelerated decline in lung function. Therefore, periodic monitoring of pulmonary function among RA patients started on MTX could be necessary. | |
| 12233877 | Tumor necrosis factor-alpha receptor II polymorphism in patients from southern Europe with | 2002 Sep | OBJECTIVE: To define the frequency of the exon 6 tumor necrosis factor-alpha (TNF-alpha) receptor II (TNFRII) gene polymorphism in severe and mild-moderate rheumatoid arthritis (RA) and its possible influence on anti-TNF-alpha treatment responsiveness. METHODS: Two cohorts of patients with RA, the first (n = 97) defined as methotrexate responders (MTX-R) with mild-moderate synovitis, and the second (n = 78) defined as nonresponders to combination therapy and receiving anti-TNF-alpha treatment because of their severe and aggressive disease (TNF-T), were studied retrospectively and compared to age, sex, and ethnically matched controls (n = 84). In the prospective study, 66 patients with severe RA were followed over the first 6 months of anti-TNF-alpha therapy and their response was examined according to genotype. RESULTS: We observed a trend towards an increased frequency of the GG genotype in patients with severe RA (6.4%) in comparison with patients with mild-moderate disease (3.1%) and controls (1.2%). When looking at the response to anti-TNF-alpha therapy, we observed that after 12 weeks of treatment, 37.8% of the TT versus 10.7% of the TG/GG patients passed from high to medium-low disease activity (p = 0.03). CONCLUSION: In our cohorts of patients selected by response to the conventional therapy and by disease severity, our preliminary study results showed a trend towards a higher prevalence of the GG genotype for the exon 6 TNFRII polymorphism in the less responsive patients with more aggressive disease. We also found a lower degree of response to anti-TNF-alpha treatments in patients carrying the G allele. | |
| 14618373 | Lack of evidence for inhibition of angiogenesis as a central mechanism of the antiarthriti | 2005 Mar | OBJECTIVES: The aim of this study was to investigate whether methotrexate (MTX) has an antiangiogenic effect and whether this property plays a role in the control of rheumatoid arthritis (RA). METHODS: A human placenta angiogenesis assay was used to examine the antiangiogenic effects of MTX in vitro. In addition, DBA/1 mice were used to compare the antiarthritic effect of MTX in collagen-induced arthritis (CIA) and its antiangiogenic effect in a murine in vivo matrigel model for angiogenesis. RESULTS: The spreading of microvessels from placental vessel fragments was not significantly inhibited by MTX. Treatment with MTX reduced significantly the incidence of CIA in DBA/1 mice in a dose-dependent manner. However, treatment with the same doses of MTX did not significantly reduce vessel growth in subcutaneous depots of bFGF-enriched matrigel. CONCLUSION: These data support the hypothesis that inhibition of angiogenesis does not significantly contribute to the antiarthritic effect of MTX seen in patients and animal models for RA. Therefore, the combination of MTX with antiangiogenic drugs appears to be a rational strategy in the treatment of RA. | |
| 15559549 | [Focus on biological agents in rheumatoid arthritis: newer treatments and therapeutic stra | 2004 Jul | Tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 are major regulators of inflammation. TNFalpha inhibitors have been shown to be effective in treating some inflammatory diseases such as rheumatoid arthritis. TNFalpha inhibitors include soluble receptor antagonists (etanercept) and monoclonal antibodies (infliximab, adalimumab). IL-1 inhibitors (anakinra) were also developed, used in therapeutics and licensed in France. TNFalpha inhibitors can be added to background regimens of methotrexate in second-line treatments. Etanercept and adalimumab can be administered alone, especially to patients who have experienced methotrexate toxicity or who do not show clinical and/or radiological improvement. The use of these new agents may optimise rheumatoid arthritis treatment and delay disease progression, particularly when first-line treatments are disappointing. This paper reviews recent data on biological therapies for rheumatoid arthritis: tolerance and their ability to modify the course of disease and prevent radiological damage. | |
| 15494900 | Cytomegalovirus retinitis in a patient treated with anti-tumor necrosis factor alpha antib | 2004 Nov 1 | BACKGROUND: Anti-tumor necrosis factor alpha (anti-TNF- alpha ) antibodies have been used for the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis arthritis. Such antibody therapies result in a severe interference with the patient's immune system. Increased rates of upper respiratory tract infection, reactivation of latent tuberculosis, and other systemic infectious diseases have been reported among patients receiving anti-TNF- alpha antibodies. METHODS: As a note of caution, we describe a 57-year-old woman who received therapy with anti-TNF- alpha antibodies for RA refractory to methotrexate. After almost 2 years of treatment, she developed a severe cytomegalovirus (CMV) retinitis of the right eye. RESULTS: Laboratory assays revealed an immune status with nearly total loss of the cellular immune response and partial reduction of the humoral immune response. Intravenous treatment with ganciclovir, followed by oral administration of valganciclovir, resulted in an ophthalmological remission. Cessation of immunosuppressive therapy led to partial immunological reconstitution in the patient. Six months after discontinuation of immunosuppressive therapy, CMV retinitis of the left eye occurred but was treated successfully with a second course of oral valganciclovir. CONCLUSION: In the light of this first reported case of a serious CMV infection following therapy with anti-TNF- alpha antibodies, CMV infection should be considered in symptomatic patients. |