Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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10685831 | Issues involved in a metaanalysis of rheumatoid arthritis radiographic progression. Analys | 2000 Feb | Missing data in controlled clinical trials may create uncertainty in the results of a study based on non-missing data. We used 4 approaches of sensitivity analysis to address this problem. Radiographic progression data were used from a randomized controlled trial of patients with rheumatoid arthritis treated with leflunomide, methotrexate, or placebo for 12 months as an example. The mean change from baseline of the Sharp total radiographic score was the primary efficacy variable for the evaluation of leflunomide in comparison with placebo in the retardation of radiographic progression. Computer simulations were used in some of these approaches. The proportion of missing radiographic data was 26.4%. Result from the non-missing data showed that leflunomide was highly statistically significantly better than placebo in the retardation of radiographic progression. Results from the sensitivity analysis showed that radiographic data are sufficiently robust that it is unlikely that the missing data would have changed the conclusions from the analysis based on non-missing data. The potential effect of missing data in the results of a clinical trial may be addressed by various methods of sensitivity analysis. Computer simulation can be a useful tool in some of these approaches. | |
9555126 | [Combination therapy in early rheumatoid arthritis: the COBRA study]. | 1997 Dec 13 | The scheme 'Combination therapy in rheumatoid arthritis' (COBRA) in early rheumatoid arthritis (RA) involves administration of not only sulfasalazine but also prednisolone and methotrexate during the first six months. The trial showed that the COBRA scheme over a period of 1.5 years was superior to sulfasalazine alone: less disease activity in the major part of the year of treatment, less articular damage on radiographs, fewer side effects and equal or reduced costs. An 'aggressive' treatment in patients with early RA is indicated, with (re)assessment of the use of corticosteroids. | |
10599392 | Accelerated nodulosis during methotrexate therapy for refractory rheumatoid arthritis. A c | 1999 | Accelerated nodulosis (AN) is a potential complication of methotrexate (MTX) therapy for rheumatoid arthritis (RA). We report on a 62-year old man affected by seropositive RA who developed AN after five months of MTX treatment. MTX-dose reduction was followed by rapid regression of the skin nodules. The Authors describe the typical features of AN and discuss on the pathogenetic mechanisms. | |
10554438 | Colchicine therapy for low-dose-methotrexate-induced accelerated nodulosis in a rheumatoid | 1999 Oct | Accelerated nodulosis developed on the fingers of a woman successfully treated with low dose methotrexate for rheumatoid arthritis. Colchicine therapy resulted in regression of these nodules for twelve months. To our knowledge, this is the first report in the dermatological literature on this relatively new entity in which the skin is also involved. | |
11242889 | [Cholesterol pericarditis associated with rheumatoid arthritis]. | 2001 Jan | Cholesterol pericarditis (CP) is a rare and unusual disease characterized by chronic pericardial effusion with high cholesterol concentration. Precipitation of cholesterol crystals may occur and induce inflammation and constrictive pericarditis. CP may be idiopathic, but is usually associated with a systemic disease, such as tuberculosis, myxedema, or as in our case, rheumatoid arthritis (RA). We present a 78-year-old woman with RA, typical deformities of the metacarpo- and metatarso-phalangeal joints and subcutaneous rheumatoid nodules. She was hospitalized with increasing dyspnea and weakness and a 2-dimensional transthoracic echocardiogram showed a large pericardial effusion, without tamponade. Blood cholesterol was 208 mg/dl, triglycerides 169 mg/dl, LDH 37 u/L and rheumatoid factor 2560 u; glucose, kidney, and thyroid function tests were normal and PPD test negative. Pericardiocentesis yielded 800 ml of opaque, cloudy fluid, with glucose 19 mg/dl, cholesterol 264 mg/dl (normal 20-40 mg/dl), triglycerides 169 mg/dl, LDH 5820 u/L and rheumatoid factor 40 u; viral titers and cultures for bacterial, mycobacterial and fungal infections were negative. The pericardial fluid had a distinctive scintillating, gold-paint appearance and many cholesterol crystals were evident microscopically. The patient responded to treatment with methotrexate and steroids. Factors responsible for increase in pericardial fluid cholesterol may be its liberation from injured pericardial cells and rheumatoid nodules, lysis of red cells, or lymphatic obstruction and impairment of the absorptive capacity of the pericardium. | |
11327265 | Treatment of Felty's syndrome with leflunomide. | 2001 Apr | Felty's syndrome (FS) is a rare manifestation of severe rheumatoid arthritis (RA). It is an immune mediated inflammatory process, usually treated with standard disease modifying antirheumatic drugs. We describe a case of severe FS that developed in a patient receiving methotrexate therapy for RA. Treatment with etanercept resulted in severe allergic cutaneous reactions. The patient subsequently responded to treatment with leflunomide. The response included dramatic improvement of leukopenia and neutropenia as well as excellent control of his arthritis. Leflunomide has recently been used effectively for the treatment of RA and may be useful for the management of patients with FS. | |
11201828 | [Acid-base balance parameters of the synovial fluid in patients with early-stage rheumatoi | 2000 | AIM: To study changes in acid-base balance (ABB) of synovial fluid (SF) in rheumatoid arthritis (RA) patients in respect of the disease duration, clinical symptoms and treatment. MATERIAL AND METHODS: The examination of verified RA patients included clinical, x-ray, immunological and special tests. The patients received nonsteroid antiinflammatory drugs, 2 weeks later--physiotherapy followed by 10-day basic treatment (tauredon, methotrexate or cyclophosphamide). RESULTS: Before the treatment, SF acidotic shift was found in all the patients. The shift correlated with activity of the inflammation, serologic affiliation to the rheumatoid factor, presence of systemic manifestations, x-ray signs of the articular changes in response to the treatment. Attenuation of the inflammatory process accompanies an increase in SF acidotic shift. In administration of methotrexate SF pH was higher than in the use of other drugs. CONCLUSION: Adjuvant ABB correctors are recommended for RA patients. | |
9777310 | Disease-modifying antirheumatic drugs. Using their clinical pharmacological effects as a g | 1998 Sep | Rheumatoid arthritis is a disease of unknown aetiology characterised by persistent joint swelling, functional disability and increased mortality. No curative therapy exists at present but some therapeutic agents, commonly referred to as disease-modifying drugs, offer the potential for suppression of the inflammatory activity and attenuation of the disease process. Since the precise mechanism of action of most disease modifying drugs is uncertain, the selection of a particular therapy must at present be based on the pharmacologic properties of each available agent, appropriately individualised for each clinical setting. The toxicity of disease-modifying agents often limits the dose and/or duration of therapy and makes careful monitoring mandatory. No consensus exists as to the order in which disease-modifying agents should be employed. Less toxic disease-modifying drugs such as auranofin, hydroxychloroquine, minocycline, and sulfasalazine are usually used in early and mild disease. Azathioprine, penicillamine (D-penicillamine), methotrexate and parenteral gold are usually considered to be more toxic and are most often used in the setting of progressive disease while the most toxic agents, such as chlorambucil and cyclophosphamide, are reserved for life-threatening manifestations such as vasculitis. Newer therapeutic approaches presently under study include the use of existing drugs in combination and novel biologic agents which selectively inhibit lymphocyte and cytokine activity. These strategies offer the hope of more efficacious and less toxic therapy in the future. | |
10606386 | Bone non-union after osteotomy in patients treated with methotrexate. | 1999 Dec | We describe 2 men with seronegative rheumatoid arthritis who presented non-union of bone after osteotomy of the tibia in one case and of a metatarsal bone in the second. Both patients were still being treated with oral low doses of methotrexate (MTX). After MTX was stopped, a prompt healing of the bone occurred. These observations suggest that MTX should be stopped temporarily in cases with delayed bone healing after surgery. | |
9785392 | Cross-sectional epidemiological survey of rheumatoid arthritis patients seen in private pr | 1998 Jul | OBJECTIVE: To conduct an epidemiological study of rheumatoid arthritis patients seen by office-based rheumatologists in France (first semester of 1996). METHODS: Cross-sectional study of 1629 rheumatoid arthritis patients conducted by 373 office-based rheumatologists who volunteered for the study (one visit per patient). Each rheumatologist was to complete a 200-variable questionnaire for the first four rheumatoid arthritis patients who came to their office. RESULTS: Women contributed 81% of the sample (mean age, 57 years); 19% of patients were seen in the Paris area, 20% in the North East, 20% in the North West, 22% in the South East and 19% in the South West. Twenty-nine per cent of patients had a paid job and 21.1% (all women) were homemakers. Among the patients with a paid job, 44% were on sick leave, with the reason for the sick leave being the rheumatoid arthritis in 36% of cases. Nineteen per cent of patients had stopped working permanently because of their rheumatoid arthritis, after a mean disease duration of six years. Mean disease duration in the overall sample was eight years. The diagnosis was established within six months of symptom onset in 75% of cases. A family history of rheumatoid arthritis was found in 11% of patients and a family history of other autoimmune diseases in 2%. The disease was precipitated by a stressful life event in 17% of cases. Follow-up was being provided only by the study rheumatologist in 59% of cases and also by a general practitioner in 39%. The disease was quiescent in 9% of cases, minimally active in 32%, moderately active in 46% and severely active in 13%. Eighty-four per cent of patients were on one (78%) or more (6%) second-line drugs including methotrexate (45%), an antimalarial (17%), intramuscular gold (14%), tiopronin (9%), D-penicillamine (6%) and sulfasalazine (12%). Fifty-two per cent of patients were on steroid therapy (mean dose, 7.5 +/- 5.7 mg/d). Other drugs included nonsteroidal antiinflammatory agents (61%), analgesics (61%), gastroduodenal protective agents (45%) and anxiety-relieving agents (10%). Twenty-four per cent of patients had had one or more surgical procedures (mean, 3/patient) for their joint disease. CONCLUSION: This nation-wide epidemiological survey conducted in France provides a database on the socioeconomic and demographic characteristics of rheumatoid arthritis patients followed in private practice. | |
11093435 | The effect of HLA-DRB1 genes, rheumatoid factor, and treatment on radiographic disease pro | 2000 Nov | OBJECTIVE: To investigate the relationship between radiographic disease progression in the presence or absence of rheumatoid arthritis (RA) linked HLA-DRB1 alleles after early introduction of disease modifying antirheumatic drug therapy in patients with RA over a study period of 6 years. METHODS: One hundred nine patients of a trial comparing intramuscular (im) gold sodium thiomalate (GSTM) and im methotrexate (MTX) in early erosive RA were followed for 6 years with regular assessments of clinical and laboratory data and yearly radiographs of hands and feet, and they were typed for HLA-DRB1 genes. Radiographic progression was analyzed for an influence of rheumatoid factor (RF) status and HLA-DRB1 genes. RESULTS: Twenty-seven patients (25%) were positive for two, 46 (42%) for one, and 36 (33%) for none of the disease linked alleles. A decrease of the rate of radiographic disease progression with treatment in this group of patients was reflected by the decline in the slope of the radiographic score. Seropositive patients (n = 71, 68%) had a significantly more destructive disease course than RF negative patients. In seropositive disease, patients with a "double dose" of RA linked alleles showed a tendency to greater progression during the first 12-24 mo of treatment, but no significant difference in the longterm radiographic outcome could be detected between subgroups defined by the presence or absence of HLA-DRB1 genes. There was no significant difference throughout the study period with respect to the clinical disease course as assessed by joint swelling, C-reactive protein, and erythrocyte sedimentation rate. The majority of the seronegative population (n = 38, 32%) had a benign disease course with the exception of patients (n = 6) with the double allele; they had radiographic disease progression comparable with the seropositive patients. CONCLUSION: Our data do not provide evidence for a more aggressive disease course in patients bearing double RA linked HLA-DRB1 alleles. | |
11333342 | Leflunomide and methotrexate. | 2001 May | Methotrexate and leflunomide are both effective drugs in the treatment of patients with rheumatoid arthritis. Methotrexate has been available for many years, whereas leflunomide is a relatively new drug. Several large trials describing its efficacy and safety in comparison with both sulfasalazine and methotrexate and with placebo have been published recently. It appears that leflunomide is approximately equally effective as sulfasalazine and methotrexate. New data are also available on the mechanism of action of leflunomide especially. This drug probably acts as an immunomodulatory agent by interfering with the de novo synthesis of pyrimidines. | |
9825751 | Can collagen type II sustain a methotrexate-induced therapeutic effect in patients with lo | 1998 Oct | OBJECTIVE: Based on the results of two recently published, randomized, double-blind and placebo-controlled studies, a possible improvement in rheumatoid arthritis disease activity after oral tolerization with triple helical collagen type II has been suggested. The goal of this study was to go one step further and ask the question whether collagen type II can sustain the therapeutic effect induced by methotrexate, the most widely accepted disease-modifying anti-rheumatic drug in patients with long-standing rheumatoid arthritis. METHODS: Ninety-two patients with rheumatoid arthritis on stable therapy with methotrexate were enrolled in a 3 month double-blind, randomized and comparative study to examine the efficacy of oral triple helical collagen type II as compared to continuing methotrexate. The dose of methotrexate (or the respective placebo drug) and of concomitant corticosteroids was not changed and intra-articular corticosteroids were not allowed during the 3 months. The primary study endpoint was disease activity as measured by physician and patients. RESULTS: While patients under ongoing therapy with methotrexate had, as expected, no change in disease activity, almost all parameters of disease activity and outcome in patients under a daily oral dose of 0.5 mg triple helical collagen type II worsened significantly (highly significant difference in swollen joints, between the two groups, P < 0.0001). No significant differences in side-effects between the two groups during the study period could be demonstrated. CONCLUSIONS: Substitution of methotrexate with daily 0.5 mg of triple helical collagen type II in patients with rheumatoid arthritis leads to a significant increase in disease activity, suggesting that oral collagen type II at the given dose is not capable of sustaining the methotrexate-induced anti-inflammatory effect in patients with long-standing rheumatoid arthritis. | |
11299072 | Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disor | 2001 Mar | The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-alpha (TNFalpha) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of beta-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include the n-3 compounds, some of which are precursors of eicosanoid synthesis, and the n-6 group which can increase formation of the pro-inflammatory cytokines TNFalpha and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so that n-3 PUFA often oppose the inflammatory effects of some n-6-PUFA. gamma-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich in n-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis. | |
11096166 | Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis | 2000 Nov 30 | BACKGROUND: Neutralization of tumor necrosis factor a (TNF-alpha) for three to six months reduces the symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known. METHODS: We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab, a chimeric monoclonal antibody against TNF-alpha, in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks. We assessed clinical responses with use of the criteria of the American College of Rheumatology, the quality of life with a health-status questionnaire, and the effect on joint damage radiographically. RESULTS: The combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone (clinical response, 51.8 percent vs. 17.0 percent; P<0.001). The quality of life was also significantly better with infliximab plus methotrexate than with methotrexate alone. Radiographic evidence of joint damage increased in the group given methotrexate, but not in the groups given infliximab and methotrexate (mean change in radiographic score, 7.0 vs. 0.6, P<0.001). Radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response. CONCLUSIONS: In patients with persistently active rheumatoid arthritis despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage. | |
9361165 | Perioperative use of methotrexate in patients with rheumatoid arthritis undergoing orthope | 1997 Nov | Methotrexate (MTX) is commonly prescribed for the treatment of rheumatoid arthritis. Its use seems to be an independent risk factor for infection with common pathogens and opportunistic organisms. Some rheumatologists and orthopedic surgeons hold the opinion that MTX should be temporarily withheld to lessen the likelihood of postoperative infection or poor wound healing. Alternatively, some clinicians believe that MTX should be continued throughout the perioperative period to avoid flares in rheumatoid arthritis disease activity. There are no definitive studies on which to rely in this decision-making process, but the authors believe that withholding MTX for 2 weeks of the perioperative period is a reasonable and prudent approach. | |
10577301 | Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arth | 1999 Nov 16 | The traditional "pyramid" or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti-inflammatory drug for months to years while seeking to avoid use of second-line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a "preventive" strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used "anchor drug" in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades. | |
11055831 | Pulmonary nodule and aggressive tibialis posterior tenosynovitis in early rheumatoid arthr | 2000 | We report the case of a 34-year-old man with a rheumatoid pulmonary nodule preceding the development of articular symptoms of rheumatoid arthritis. Pulmonary nodules are a well known feature of rheumatoid arthritis and are mostly seen in severe established rheumatoid factor-positive cases. To differentiate between benign and malign pulmonary nodules we discuss the use of positron emission tomography (PET). Despite intensive therapy with steroids and methotrexate in our patient, within months he developed a severe tibialis posterior tendinitis, with partial rupture and evolution to a planovalgus deformity requiring surgery. Both these symptoms are rare but demonstrate the need for close follow-up in early rheumatoid arthritis. | |
9870779 | Methotrexate-induced hepatic necrosis requiring liver transplantation in a patient with rh | 1998 Jul | MTX-induced hepatic injury and liver enzyme elevations have been demonstrated after treatment of leukemia, gestational disease and during treatment of psoriasis and rheumatoid arthritis. A 40-year-old man with a long standing history of rheumatoid arthritis was treated with MTX over a 6 month period and developed an overwhelming hepatic necrosis. He was successfully transplanted. | |
10685827 | A review of controlled clinical trials examining the effects of antimalarial compounds and | 2000 Feb | At least 8 randomized controlled clinical trials have examined the effects of chloroquine or hydroxychloroquine on radiographic progression in rheumatoid arthritis (RA). At least 12 randomized controlled trials have examined the effects of either intramuscular or oral gold on radiographic progression. A review of these studies shows that hydroxychloroquine and chloroquine have minimal, if any, inhibitory effects on radiographically documented progression of bone erosions and joint destruction when used to treat RA. Intramuscular gold (with most of the data from studies of sodium aurothiomalate) appears to be better than placebo, about equal to intramuscular methotrexate (MTX), but probably not as effective as cyclophosphamide or azathioprine in its effects on radiographic progression. Auranofin appears to be better than placebo, comparable to or perhaps moderately less effective than intramuscular gold, comparable to lower dose oral MTX (7.5 mg/week), and not as effective as higher dose oral MTX (7.5-15 mg/wk) in inhibiting radiographic progression in RA. The inhibitory effects of gold compounds on proinflammatory cytokine synthesis (especially interleukin 1) offer a plausible mechanism for their inhibitory effects on bone erosion and joint destruction in RA. |