Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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21128990 | Eternacept for the treatment of patients with rheumatoid arthritis and concurrent intersti | 2012 Feb | WHAT IS KNOWN AND OBJECTIVE: Tumour necrosis factor-α (TNF-α)-blocking agents are increasingly used in the management of refractory rheumatoid arthritis (RA). Although effective, they are associated with rare but potentially fatal adverse effects, including interstitial lung disease (ILD). In patients with pre-existing ILD, eternacept (ETN) monotherapy is often regarded as a suitable choice. Other anti-TNF-α blockers such as infliximab and adalimumab, are used in combination therapy with methotrexate (MTX) in most of the cases. We report on a case of fatal exacerbation of ILD in a patient given ETN monotherapy and review the literature on ETN-associated ILD. METHODS: We report on a case of a 75-year-old male with RA who developed severe ILD after the introduction of ETN, and we undertook a literature search to identify other reports of similar cases. We then critically assessed those reports. RESULTS AND DISCUSSION: In addition to our case, 11 other patients have been reported to have developed ILD in association with the use of ETN. Six patients had pre-existing ILD. Although four patients received MTX, eight patients developed severe ILD without MTX. Ten patients recovered after termination of ETN, although two patients died. WHAT IS NEW AND CONCLUSION: Although ETN is often regarded as safe for patients with ILD, our case and the literature reports suggest that caution is still required. | |
19603251 | Long-term efficacy of leflunomide on disease activity and inhibition of joint damage: retr | 2009 | We retrospectively compared treatment impact with leflunomide (LEF) or methotrexate (MTX) on retarding joint damage and clinical symptom including a 28-joint-count Disease Activity Score/erythrocyte sedimentation rate (DAS28-ESR) between two similar groups in patients with rheumatoid arthritis (RA) over an approximately 3-year treatment. One group included 29 patients treated with LEF alone (average dose 16.1 mg/day); the other group included 26 patients treated with MTX (average dose 7.4 mg/week) alone or combined with other disease-modifying antirheumatic drugs. At baseline, mean disease duration was 7.1 and 6.9 years, and mean DAS28-ESR was 5.79 and 5.69, respectively. The average DAS28-ESR improvement of 1.750 (from 5.79 to 4.04) in the LEF-treated group was significantly greater than the effect of 1.007 (from 5.69 to 4.68) seen in the MTX group (P = 0.0455), with the same results being observed on European League Against Rheumatism (EULAR) response criteria. Annual changes observed in Larsen score in total joints were 0.030 in the LEF group and 0.085 in the MTX group: LEF retards joint damage significantly better than MTX (P = 0.003). This inhibitory effect was better in small joints (P = 0.004) than in middle and large joints (P = 0.075). A negative correlation was noticed between improved DAS28-ESR and the progression of joint damage in the LEF group (r = -0.7068, P < 0.0001), whereas there was no correlation in the MTX group (r = -0.0311, P = 0.882). In daily clinical practice, LEF showed significant clinical and radiological improvement compared with the standard MTX regimen in Japan. | |
19894782 | Certolizumab pegol: in rheumatoid arthritis. | 2009 | Certolizumab pegol is a PEGylated humanized Fab' monoclonal antibody that targets and neutralizes both membrane-bound and soluble tumor necrosis factor (TNF)-alpha, preventing inflammation and consequently the destruction of cartilage and bone. Certolizumab pegol has a relatively long elimination half-life of approximately 2 weeks, allowing subcutaneous administration once every 2 or 4 weeks. In two randomized, phase III trials in patients with active rheumatoid arthritis despite previous methotrexate therapy (RAPID 1 and 2), the combination of subcutaneous certolizumab pegol 400 mg at weeks 0, 2, and 4, followed by a 200 or 400 mg dose every 2 weeks and a stable dosage of methotrexate, was more effective than placebo plus methotrexate for improving the signs and symptoms of arthritis at weeks 24 (RAPID 1 and 2) and 52 (RAPID 1), according to American College of Rheumatology (ACR) criteria. Improvements in ACR response rates were seen as early as 1 week and at all timepoints measured up to 52 weeks. In RAPID 1 and RAPID 2, radiographic progression was also significantly inhibited with certolizumab pegol plus methotrexate treatment compared with placebo and methotrexate according to van der Heijde modified Total Sharp Scores at 24 and 52 weeks after treatment initiation. In patients with active rheumatoid arthritis who had previously failed to respond to treatment with > or = 1 disease-modifying anti-rheumatic drug, certolizumab pegol 400 mg every 4 weeks as monotherapy effectively improved ACR responses at all measured timepoints up to 24 weeks, according to data from the randomized, phase III FAST4WARD trial. Certolizumab pegol was generally well tolerated in combination with methotrexate or as monotherapy in phase III trials in patients with rheumatoid arthritis, with most adverse events being of mild to moderate intensity. Infections were the most frequently reported adverse events. | |
18388156 | Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an i | 2009 Feb | OBJECTIVE: To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors. METHODS: In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56. RESULTS: Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001). CONCLUSIONS: This study provides the first evidence that a B cell-targeted therapy-rituximab-can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease. | |
19538718 | Use of risk stratification to target therapies in patients with recent onset arthritis; de | 2009 Jun 18 | BACKGROUND: Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis. METHODS: A multicenter stratified randomized single-blind controlled trial is currently being performed in patients 18 years or older with recent-onset arthritis. Eight hundred ten patients are being stratified according to the likelihood of their developing persistent arthritis. In patients with a high probability of persistent arthritis, we will study combination Disease Modifying Antirheumatic Drug therapy compared to monotherapy methotrexate. In patients with an intermediate probability of persistent arthritis, we will study Disease Modifying Antirheumatic Drug of various intensities. In patients with a low probability, we will study non-steroidal anti-inflammatory drugs, hydroxychloroquine and a single dose of corticosteroids. If disease activity is not sufficiently reduced, treatment will be adjusted according to a step-up protocol. If remission is achieved for at least six months, medication will be tapered off. Patients will be followed up every three months over two years. DISCUSSION: This is the first rheumatological study to base treatment in early arthritis on a prediction rule. Treatment will be stratified according to the probability of persistent arthritis, and different combinations of treatment per stratum will be evaluated. Treatment will be started early, and patients will not need to meet the ACR-criteria for rheumatoid arthritis. TRIAL REGISTRATION: This trial has been registered in Current Controlled Trials with the ISRCTN26791028. | |
19690125 | The effect of etanercept on work productivity in patients with early active rheumatoid art | 2009 Oct | OBJECTIVES: To compare the impact of the combination of etanercept (ETN) and MTX with MTX alone on work productivity among MTX-naïve patients with active early RA over a 12-month period. METHODS: The COMET (COmbination of Methotrexate and ETanercept) trial was a 2-year double-blind randomized clinical trial. Absenteeism during the first year was measured and it included: (i) number of missed workdays; (ii) reduced working time; and (iii) number of stopped workdays. Each absenteeism measure was estimated using a mixed model, and their variations were estimated by bootstrapping. As a sensitivity analysis, the lost workdays due to presenteeism (reduced performance at work) was also estimated. RESULTS: Two hundred and five patients [MTX (n = 100) vs ETN + MTX (n = 105)], who were working full time or part time at baseline and had at least one follow-up observation, were included in the analysis. Compared with the MTX group, the ETN + MTX group had a maximum of 37 fewer missed workdays or at minimum 22 fewer missed workdays. The associated productivity gain equalled 2586 pounds and 1555 pounds, respectively. When additionally accounting for presenteeism, the total improvement could be as high as 42 (95% CI 16, 69) fewer lost workdays representing a productivity gain of 2968 pounds. CONCLUSIONS: Our results demonstrated that early treatment with ETN + MTX led to a significant attenuation of absenteeism among patients with early active RA. These productivity gains represent benefit beyond the traditional measures of clinical and radiographic improvements. Further research to simultaneously measure both absenteeism and presenteeism is warranted. | |
20099018 | Evaluation of abatacept in biologic-naïve patients with active rheumatoid arthritis. | 2010 Jun | This article reviews the efficacy, safety, and tolerability of abatacept plus methotrexate in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate who are naïve to biologic disease-modifying antirheumatic drugs (DMARDs). Data from the randomized, double-blind, placebo-controlled Abatacept in Inadequate Responders to Methotrexate, Abatacept or Infliximab vs Placebo, a Trial for Tolerability, Efficacy, and Safety in Treating Rheumatoid Arthritis, and phase IIb dose-finding trials and their long-term extensions are reviewed. Abatacept plus methotrexate significantly improved clinical responses, physical function, and health-related quality of life compared with methotrexate alone. More patients receiving abatacept plus methotrexate than methotrexate monotherapy achieved a low disease activity state or remission. Radiographic progression of the disease was significantly slowed in the abatacept plus methotrexate arms. Abatacept plus methotrexate was generally well tolerated with no clinically significant safety issues identified. The beneficial effects of abatacept plus methotrexate were sustained long term in extension studies, and no new tolerability or safety issues were evident. Abatacept in combination with methotrexate is an effective, safe, and well-tolerated long-term therapy in biologic-naïve patients with active RA and an inadequate response to methotrexate. Abatacept could be considered as a first-line biologic DMARD in the treatment of RA. | |
20110520 | Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. | 2010 Mar | OBJECTIVE: To evaluate the longterm safety of rituximab in clinical trials in patients with rheumatoid arthritis (RA). METHODS: Pooled analysis of safety data, including adverse events (AE) and infections, from patients treated with rituximab in combination with methotrexate in a global clinical trial program. RESULTS: A total of 2578 patients with RA received at least 1 course of rituximab. Safety analyses were based on 5013 patient-years of rituximab exposure. The most frequent AE was infusion-related reactions (25% of patients during the first infusion of Course 1). Less than 1% of infusion-related reactions were considered serious. Rates of AE and serious AE (SAE; 17.85 events/100 patient-yrs, 95% CI 16.72, 19.06) were stable following each course. The overall serious infection rate was 4.31/100 patient-years (95% CI 3.77, 4.92). Infections and serious infections over time remained stable across 5 courses at 4-6 events/100 patient-years. Compared with other patients with RA and with the general US population, there was no increased risk of malignancy. CONCLUSION: In this longterm safety update in RA clinical trial patients, rituximab remained well tolerated over multiple courses. SAE and infections remained stable over time and by treatment course. | |
20703487 | [Selective co-stimulation blockade. CTLA4-Ig (Abatacept)]. | 2010 Sep | Abatacept is a soluble fusion protein comprising the extracellular domain of human CTLA4 linked to the modified Fc portion of human IgG(1). It is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate and juvenile chronic arthritis by blocking the co-stimulatory signal required for full T-cell activation. Abatacept has added to the growing armamentarium of targeted therapies for RA, including the challenging group of RA patients who are refractory to TNF-alpha blockade. To date, abatacept has its main application in cases failing to respond to TNF-alpha blockade. In several studies, the efficacy and safety of abatacept was not only shown for TNF-IR patients, but also for DMARD-IR patients. Recently, the EU has approved abatacept in combination with methotrexate in DMARD-IR patients. The significant and similar response rates in TNF-alpha blockade failure to those observed in only DMARD failure implies that the pathways targeted with the two treatments remain distinct. In terms of safety profile, incidence rates of malignancy in the abatacept trials were consistent with those in a comparable RA population. The rate of opportunistic infections does not seem to be increased in patients treated with abatacept. | |
20961415 | Identification of a cytokine network sustaining neutrophil and Th17 activation in untreate | 2010 | INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). METHODS: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. RESULTS: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1β and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. CONCLUSIONS: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis. | |
20950476 | A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to | 2010 | INTRODUCTION: Preclinical work has suggested that IL-1 plays a critical role in the pathogenesis of rheumatoid arthritis (RA). The objective of the present study was to determine the effect of a long-acting IL-1 receptor inhibitor, AMG 108, in a double-blind, placebo-controlled, parallel-dosing study in patients with active RA who were receiving stable methotrexate (15 to 25 mg/week). METHODS: Patients were randomized equally to receive placebo or 50, 125, or 250 mg AMG 108 subcutaneously every 4 weeks for 6 months. The primary efficacy endpoint was a 20% improvement in the American College of Rheumatology response (ACR20) at week 24; other efficacy endpoints included the ACR50, the ACR70, and the RA disease activity score (28-joint count Disease Activity Score) responses, patient-reported outcomes, and pharmacokinetic parameters. Safety endpoints included treatment-emergent adverse events (AEs), infectious AEs, serious AEs, serious infections, injection site reactions, laboratory abnormalities, and antibodies to AMG 108. RESULTS: Of 813 patients enrolled in the study, 204 patients were randomized to the 50 mg group, 203 to the 125 mg group, 203 to the 250 mg group, and 203 to placebo. At week 24, 40.4% of the 250 mg group, 36% of the 125 mg group, 30.9% of the 50 mg group, and 29.1% of the placebo group achieved an ACR20 (P = 0.022, 250 mg vs. placebo). Of the individual ACR components, numerical dose-dependent improvements were only seen in tender joint counts, pain (visual analog scale), and the acute phase reactants, erythrocyte sedimentation rate and C-reactive protein. No dose-related increase was observed in the incidence of treatment-emergent AEs. No deaths were reported, and the incidence of AEs and infections, serious AEs and infections, and withdrawals from study for safety were similar in the AMG 108 and placebo groups. CONCLUSIONS: This large double-blind randomized trial with a long-acting IL-1 receptor blocker, AMG 108, is consistent with the experience of other IL-1 blockers, represents a definitive experiment showing that IL-1 inhibition provides only moderate symptomatic amelioration of arthritis activity in the majority of RA patients, and provides an answer to a question that has been discussed for many years in the rheumatologic community. TRIAL REGISTRATION: ClinicalTrials.gov NCT00293826. | |
19229766 | Contemporary use of disease-modifying drugs in the management of patients with early rheum | 2009 | OBJECTIVE: As treatment options for rheumatoid arthritis (RA) are rapidly expanding, we evaluated the current use of disease-modifying anti-rheumatic drugs (DMARDs) in the management of patients with early RA in Norway with particular attention to the influence of risk factors for a poor disease outcome on DMARD selection. METHODS: An observational multicentre study registering the type of therapy initiated in 820 DMARD-naive patients with early active RA [67% female, mean age 51 years, disease duration 4 months, 57% rheumatoid factor (RF) positive]. The impact of baseline risk factors associated with poor prognosis (disease activity parameters and biomarkers of inflammation) on DMARD selection was analysed through odds ratios (ORs) by multivariate logistic regression. RESULTS: Methotrexate (MTX) monotherapy was selected for 78% of patients. MTX was preferred over sulfasalazine (SSZ) monotherapy (19%), leflunomide monotherapy (2%), and combination therapy (2%) in female patients [OR 1.6, 95% confidence interval (CI) 1.1-2.5], age >50 years (OR 2.5, 95% CI 1.6-3.8), short disease duration (OR 2.7, 95% CI 1.4-5.0), 10 swollen joints (OR 2.2, 95% CI 1.2-4.0), and erosive disease (OR 1.8, 95% CI 1.1-3.2). Concurrent steroid therapy was started in 73% of patients, regardless of the type of DMARD therapy initiated. CONCLUSION: Monotherapy with MTX is currently the DMARD treatment of choice for early RA in Norway. Disease duration, age, swollen joint count, and erosive disease have considerable impact on DMARD selection in contrast to the presence of biomarkers. Few patients with early RA in Norway receive combination DMARD therapy, while the majority of patients receive corticosteroid bridging therapy. | |
20525444 | Normalisation of physical function by infliximab in patients with RA: factors associated w | 2010 May | OBJECTIVES: We conducted a two-year prospective study to identify possible factors associated with normalisation of physical function by infliximab treatment in 125 patients with rheumatoid arthritis (RA). METHODS: RA patients who had been scheduled to receive infliximab at 3 mg/kg were registered and prospectively examined for disease activity, joint damage, and physical function for 102 weeks using the Disease Activity Score of 28 Joints (DAS-28) using C-reactive protein, van der Heijde-modified Sharp score (vdH-Sharp score) of hand and foot x-ray, and Health Assessment Questionnaire Disability Index (HAQ-DI). Normal physical function and clinical remission were defined as a HAQ-DI of 0.5 or less, and DAS28 (CRP) <2.6, respectively. RESULTS: Forty-two of 125 patients (42%) achieved normal physical function at 102 weeks. The percentage of normal physical function at 102 weeks was significantly higher in the patients achieving clinical remission at 102 weeks (60%) than in those without (16%). In the patients with clinical remission at 102 weeks, less structural damage at baseline was correlated with a higher rate of normal physical function, suggesting the critical importance of joint destruction prior to infliximab therapy, in addition to clinical response. Logistic regression analysis further identified HAQ-DI, serum MMP-3 level, vdH-Sharp score, and methotrexate (MTX) dose as baseline factors contributing to normal physical function with 2-year infliximab treatment. CONCLUSIONS: Treatment with anti-TNF biologics in combination with MTX may achieve the normalisation of physical function in patients with established RA. Critical factors contributing to the normalisation of function were tight control of disease activity and less joint damage. | |
19948435 | Improvement of active rheumatoid arthritis after etanercept injection: a single-center exp | 2009 Nov | BACKGROUND: To study the clinical effectiveness and adverse reactions of etanercept in patients with active rheumatoid arthritis (RA), in whom combination therapies with disease-modifying antirheumatic drugs (DMARDs) had failed. METHODS: One hundred and thirty-three patients with active RA who had been treated without satisfactory effect with DMARDs were entitled, by the Taiwan Bureau of National Health Insurance, to undergo etanercept injection (25 mg subcutaneously, twice weekly) along with oral methotrexate (15 mg weekly) in Taipei Veterans General Hospital. The disease activity score in 28 swollen and 28 tender joints (DAS28), erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), rheumatoid factors (RFs), tender joint count (TJC), and swollen joint count (SJC) were recorded at the beginning, 3, 6, 9, and 12 months after treatment. Any adverse event, relevant or irrelevant to the therapy, was recorded throughout the whole course of treatment. RESULTS: Ninety-four patients completed the 1-year therapeutic program. There were significant improvements in all parameters (DAS28, ESR, CRP, TJC and SJC), which approached satisfactory values at the end of the first 3 months and which were sustained thereafter in most patients. Patients also tolerated the treatment protocol well, with adverse events occurring sporadically. Significant clinical response occurred as early as 3 months after the start and might last beyond 1 year in some patients. Adverse effects such as injection site reaction or infections rarely occurred. CONCLUSION: Combination therapy with etanercept and DMARDs seemed to be effective at improving the aching symptoms associated with rheumatoid activity and was well tolerated in this cohort study. It was generally safe, though a small number of non-fatal infections were observed. | |
19787419 | Prediction of DAS28-CRP remission in patients with rheumatoid arthritis treated with tacro | 2009 | We attempted to determine what baseline variables are responsible for the efficacy of tacrolimus at 6 months in Japanese patients with rheumatoid arthritis (RA). One hundred and six RA patients treated with tacrolimus for 6 months were entered in this study. The outcome was set as the achievement of Disease Activity Score 28 C-reactive protein (DAS28-CRP) remission at 6 months. We examined the association of gender, DAS28-CRP at baseline, concomitant use of methotrexate (MTX), and concomitant use of prednisolone with the achievement of DAS28-CRP remission at 6 months by logistic regression analysis. Twenty-three of 106 patients (21.7%) achieved DAS28-CRP remission at 6 months. There was concomitant use of MTX by 20 patients (18.9%), prednisolone by 93 (87.7%), and prednisolone [5 mg/day by 43 (40.6%) at baseline. Logistic regression analysis showed that male gender (first) and moderate disease activity at baseline (second) are independent predictors toward achieving DAS28-CRP remission at 6 months. Maximum tacrolimus dosage administrated for patients over a 6-month period appeared not to be predictive for the DAS28-CRP remission at 6 months. In conclusion, we revealed for the first time that good outcome in RA patients treated with tacrolimus can be predictive by some baseline variables. That is clinically valuable for daily practice in the choice of disease-modifying antirheumatic drugs (DMARDs), especially tacrolimus. | |
20943048 | Can Cyclosporine-A associated to methotrexate maintain remission induced by anti-TNF agent | 2010 Jul | Biological therapies, such as etanercept, adalimumab and infliximab, have demonstrated good efficacy in inducing rheumatoid arthritis to low disease activity levels. Nevertheless, their cost, as well as the related risk of side effects, especially in long-term therapies, are still high. Furthermore, there is a good deal of evidence proving loss of efficacy of such therapies in the long term, often necessitating the shift from one specific anti-TNF biological treatment to another. There are also other open debates on the amount of time a patient should undergo an anti-TNF therapy, on the possibility of inducing a complete remission in early arthritis and, once remission or low disease activity is obtained, on the possibility of interrupting the anti-TNF-based therapy. In this study we investigated whether A-Cyclosporin and Methotrexate association may be effective in maintaining low disease activity obtained by anti-TNF therapies. Twenty-three rheumatoid arthritis-affected patients, whose diagnosis was made according to ACR criteria, with a disease duration of less than 3 years, and DAS28<3.2 that reached a level of low disease activity within 6-8 months from beginning anti-TNF and Methotrexate therapy, were enrolled in the study. After the suspension of anti-TNF therapy, patients were started on A-Cyclosporine (2-3 mg/kg/day) and Methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation Rate (ESR), and C Reactive Protein (CRP) were all tested at time 0 and at 6 months, as well as liver and kidney profiles, after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and Methotrexate therapy. Side effects were also recorded. Of 23 patients undergoing the A-Cyclosporin and Methotrexate therapy for maintaining low disease activity in rheumatoid arthritis obtained by 6-8 months of anti-TNF therapy, 21 completed the study with a 6 month follow-up. Thirteen patients maintained clinical parameters within low disease activity values, while 8 patients showed an increase in DAS28 and other parameters. Only two patients showed an increase in blood pressure that was diagnosed after two months from the beginning of the A-Cyclosporin and Methotrexate therapy. The reduction in the dosage of A-Cyclosporin from 3mg/kg/day to 2mg/kg/day caused a slow normalization of blood pressure values. Our data seem to suggest that more than half of the patients undergoing A-Cyclosporin and Methotrexate therapy seemed to maintain low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses. | |
21041278 | Effect of atorvastatin on inflammation and modification of vascular risk factors in rheuma | 2011 Feb | OBJECTIVE: To investigate the effect of atorvastatin therapy on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: This study included 30 patients with early RA, randomly divided into 2 groups. Group 1 (n = 15) received methotrexate (MTX; 0.2 mg/kg/week; mean (15.5 ± SD 1.3) plus prednisone (10 mg/day). Group 2 (n = 15) received MTX and prednisone with the same previous doses plus atorvastatin therapy (40 mg/day). Ten healthy individuals of similar age and sex served as controls. Disease activity, lipid profile, serum malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), resistin, adiponectin, and brachial artery flow-mediated dilation (FMD) were measured before and after 6 months of treatment. RESULTS: Atorvastatin combined with MTX therapy significantly reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and increased high-density lipoprotein cholesterol (p < 0.001). Disease activity variables, serum MDA, TNF-α, resistin, adiponectin, and FMD were significantly improved by the drug combinations (p < 0.001). CONCLUSION: Atorvastatin therapy in patients with RA reduced disease activity and conventional and novel vascular risk factors that promote the atheromatous lesion. Therapy was also associated with concomitant improvement in endothelial function. | |
20439295 | Continued inhibition of structural damage over 2 years in patients with rheumatoid arthrit | 2010 Jun | BACKGROUND: Rituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors. OBJECTIVE: To assess structural damage progression through 2 years. METHODS: Intention-to-treat patients with one post-baseline radiograph (rituximab n=281; placebo n=187) received background methotrexate (MTX) and were randomised to rituximab (2 x 1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months. By week 104, 82% of the placebo population had received > or = 1 dose of rituximab. Radiographic end points included the change in total Sharp score (TSS), erosion and joint space narrowing scores at week 104. RESULTS: At week 104, significantly lower changes in TSS (1.14 vs 2.81; p<0.0001), erosion score (0.72 vs 1.80; p<0.0001) and joint space narrowing scores (0.42 vs 1.00; p<0.0009) were observed with rituximab plus MTX vs placebo plus MTX. Within the rituximab group, 87% who had no progression of joint damage at 1 year remained non-progressive at 2 years. CONCLUSIONS: Rituximab plus MTX demonstrated significant and sustained effects on joint damage progression in patients with RA and a previously inadequate response to TNF inhibitors. | |
19644884 | Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug effic | 2009 Aug | OBJECTIVE: To assess the catabolism of methotrexate (MTX) to 7-hydroxy-MTX (7-OH-MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism. METHODS: Urinary excretion of MTX and its catabolite, 7-OH-MTX, was measured in 2 24-hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7-OH-MTX concentrations were determined by high-performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7. RESULTS: Folic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7-OH-MTX, but folinic acid did not. Excretion of 7-OH-MTX (determined as a percentage of the dose of MTX or as mg 7-OH-MTX/gm creatinine) was not normally distributed (n=39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7-OH-MTX excretion level (P<0.05). Patients who received folic acid supplements had decreased 7-OH-MTX excretion (P=0.03). Relatively high 7-OH-MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P<0.05) (n=35). CONCLUSION: Our findings of a non-normal distribution of 7-OH-MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo. | |
19359261 | Association of methotrexate and tumour necrosis factor antagonists with risk of infectious | 2010 Feb | OBJECTIVE: To examine the association of methotrexate (MTX) and tumour necrosis factor (TNF) antagonists with the risk of infectious outcomes including opportunistic infections in patients with rheumatoid arthritis (RA). METHODS: Patients with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease-modifying antirheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using generalised estimating equation Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures. RESULTS: A total of 7971 patients with RA were followed. The adjusted rate of infections per 100 person-years was increased among users of MTX (30.9, 95% CI 29.2 to 32.7), TNF antagonists (40.1, 95% CI 37.0 to 43.4) and a combination of MTX and TNF antagonists (37.1, 95% CI 34.9 to 39.3) compared with users of other non-biological DMARDs (24.5, 95% CI 21.8 to 27.5). The adjusted incidence rate ratio (IRR) was increased in patients treated with MTX (IRR 1.30, 95% CI 1.12 to 1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30 to 1.78) compared with those treated with other DMARDs. TNF antagonist use was associated with an increased risk of opportunistic infections (IRR 1.67, 95% CI 0.95 to 2.94). Prednisone use was associated with an increased risk of opportunistic infections (IRR 1.63, 95% CI 1.20 to 2.21) and an increased risk of overall infection at doses >10 mg daily (IRR 1.30, 95% CI 1.11 to 1.53). CONCLUSIONS: MTX, TNF antagonists and prednisone at doses >10 mg daily were associated with increased risks of overall infections. Low-dose prednisone and TNF antagonists (but not MTX) increased the risk of opportunistic infections. |