Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 10461858 | The effect of tryptophan plus methionine, 5-azacytidine, and methotrexate on adjuvant arth | 1999 Aug | Within the wider framework of our studies on the genesis of rheumatoid arthritis we have investigated the two signal processes in arthritis: adenoribosylation of proteins and DNA methylation. Arthritis can be induced when Freund's complete adjuvant is applied to rats. This form of arthritis can then be reduced or even totally suppressed through the application of several different substances. In the present article we have investigated if the effect of two of these substances, 5-azacytidine and methotrexate can be influenced by the application of tryptophan plus methionine. When applied singly, these latter two substances are known to reduce the formation of arthritis. This effect is intensified by a combination of tryptophan plus methionine. Application of tryptophan plus methionine without methotrexate or 5-azacytidine causes an enhanced development of an adjuvant induced arthritis. | |
| 9633020 | Bone turnover is reduced in children with juvenile rheumatoid arthritis. | 1998 Jan | Juvenile Rheumatoid Arthritis (JRA) is frequently associated with osteoporosis. In order to determine if JRA osteoporosis is related to reduced formation or to increased bone resorption or both, serum levels of calcium (Ca), phosphorus (PO4), magnesium (Mg), alkaline phosphatase (ALP), parathormone (PTHi), 25-hydroxyvitamin D3 (25-OHD) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D), osteocalcin (OT), carboxyterminal propeptide (P-coll-1-c), and carboxyterminal telopeptide of type I collagen (ICTP) were evaluated in 47 JRA children, 33 with active disease and 14 in remission. The therapy consisted of nonsteroidal antiinflammatory (NSAIDs) drugs in pauciarticular subset, NSAIDs and Methotrexate (MTX) in polyarticular, NSAIDs and steroids in systemic onset. OT reflects bone formation, P-coll-1-c reflects collagen production and bone formation, ICTP, marker of collagen degradation in bone, indicates bone destruction. Serum levels of Ca, PO4, Mg, ALP, PTHi 25-OHD and 1,25-(OH)2D were comparable in JRA children and in controls. OT (8.7 +/- 3.7 ng/ml vs 9.6 +/- 5.1), P-coll-1-c (301.2 +/- 118.4 ng/ml vs 264.1 +/- 100.1) and ICTP (15.7 +/- 5.7 ng/ml vs 16.1 +/- 6.1) did not differ statistically in the whole group of JRA children vs controls. OT (8.0 +/- 3.5 vs 10.4 +/- 3.8) and ICTP (14.4 +/- 5.4 vs 18.8 +/- 5.4) were significantly lower in active than inactive group. In polyarticular and systemic onset OT and ICTP were significantly lower than in pauciarticular. No difference was found in active patients treated with steroids vs active patients treated with NSAIDS and NSAIDs plus MTX. The lower serum levels of OT and ICTP in active disease support the hypothesis that both bone formation and resorption are reduced in JRA bone turnover. | |
| 10969505 | Efficacy and safety of methotrexate therapy for juvenile rheumatoid arthritis. | 2000 Aug | BACKGROUND AND PURPOSE: Juvenile rheumatoid arthritis (JRA) can result in disability, growth disturbance, and systemic complications. This study investigated the efficacy and adverse effects of oral methotrexate (MTX) therapy in Taiwanese children with JRA. METHODS: The medical records of 52 Taiwanese children with JRA treated with oral MTX were retrospectively analyzed. The disease onset was polyarticular in 22 children, oligoarticular in 13, and systemic in 17. The indication for MTX therapy was lack of efficacy of previous drugs, including two or more nonsteroidal anti-inflammatory drugs, in all patients. In addition, three patients had received hydroxychloroquine and one had received sulfasalazine, without improvement. Corticosteroid dependency had developed in 27 patients prior to MTX therapy. The mean initial dose of MTX was 9.1 mg.m-2.wk-1 (range, 5-20 mg.m-2.wk-1), and the mean maximal dose was 10.2 mg.m-2.wk-1 (range, 5-20 mg.m-2.wk-1). The mean duration of treatment was 23 months (range, 6-96 mo), and the mean duration of follow-up was 52 months (range, 10-123 mo) from the start of MTX therapy. RESULTS: Thirty-six children (69%) showed clinical improvement and 25 children (48%) achieved clinical remission. The administration of MTX resulted in more than a 50% reduction in required corticosteroid dosage in six children, and complete discontinuation of corticosteroid in 10 children. MTX was discontinued in 18 patients following a mean of 8 months (range, 2-34 mo) of clinical remission. Relapse occurred in nine (50%) of these patients. Thirteen patients (25%) suffered from adverse effects associated with MTX treatment. All of these adverse effects resolved spontaneously, or subsided within 4 weeks following dosage reduction or discontinuation of MTX. CONCLUSIONS: Oral MTX therapy is effective and well-tolerated in Taiwanese children with JRA. It can serve as the first choice of second-line therapy in JRA. | |
| 9698030 | Septic arthritis with Listeria monocytogenes during low-dose methotrexate. | 1998 Jul | We describe a 22-year-old female with systemic lupus erythematosus and lymphopenia, who developed septic arthritis of the right knee with Listeria monocytogenes type 1/2 A, whilst on low-dose methotrexate (MTX). So far, septic arthritis due to this microorganism has been reported in two other patients treated with low-dose MTX, one having rheumatoid arthritis and the other psoriatic arthritis. No reports exist on patients treated with other cytotoxic antirheumatic therapies. | |
| 9416861 | The long-term effect of methotrexate therapy on the liver in patients with juvenile rheuma | 1997 Dec | OBJECTIVE: To determine if the long-term use of methotrexate (MTX) in juvenile rheumatoid arthritis (JRA) is associated with the development of significant liver fibrosis, and to describe the presence of risk factors for liver fibrosis in patients with JRA. METHODS: Needle biopsies of the liver were performed on a cross-section cohort of 14 patients with JRA who had received a total cumulative dose of MTX that was either > 3,000 mg or > 4,000 mg/1.73 m2 of body surface area. Biopsy samples were independently graded according to the Roenigk Classification Scale by 2 pathologists. The presence of risk factors for MTX hepatotoxicity, especially biochemical abnormalities reflective of liver injury and alcohol consumption, were assessed. RESULTS: Thirteen biopsy samples (93%) were classified as grade I, and 1 (7%) as grade II; none demonstrated significant fibrosis. However, histologic abnormalities were found in 13 biopsy samples (93%). Only 2 patients (14%) consumed more than 1 alcoholic drink per month. Thirteen patients (93%) had biochemical abnormalities while being treated with MTX, but only 5 patients (36%) had at least 1 determination in which the aspartate or alanine aminotransferase elevation was > 3 times the upper limit of normal. CONCLUSION: Long-term use of MTX for JRA does not appear to be associated with the development of significant liver fibrosis. Although nearly all patients had minor histologic changes, no significant clinical consequences were apparent. A prospective study of a larger population will more accurately define the incidence of MTX-related liver fibrosis and appropriate monitoring guidelines in JRA. | |
| 9415655 | Preliminary evidence for cyclosporin A as an alternative in the treatment of recalcitrant | 1997 Dec | OBJECTIVE: To evaluate the safety and efficacy of cyclosporin A (CyA) with and without methotrexate (MTX) in refractory juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDMS). METHODS: Twenty-two patients (17 with JRA, 5 with JDMS) with refractory disease were studied retrospectively. All received CyA at a mean dose of 3.2 mg/kg/day over a mean period of 16 mo (range 6-42). All other medications except nonsteroidal antiinflammatory drugs, prednisone, and hydroxychloroquine were discontinued. In addition, 16/22 patients received concomitant MTX. RESULTS: Improvements in laboratory variables, joint counts, joint swelling, and morning stiffness were observed in most of the children with JRA. Muscle strength increased and muscle enzyme levels decreased in the patients with JDMS. CyA treatment permitted prednisone to be discontinued in 5/20 and reduced by greater than 50% in 10/20 patients. There was no evidence of hepatic or bone marrow toxicity or lymphoproliferative disease. Serum creatinine increased in 13/22 patients, but the actual values all remained within normal limits. CONCLUSION: CyA may be an effective agent in the treatment of refractory JRA and JDMS and concomitant MTX seems to be well tolerated. These preliminary data also suggest that combined CyA/MTX therapy may be associated with further improvement in clinical outcome. | |
| 10595864 | Medical management of children with juvenile rheumatoid arthritis. | 1999 Nov | One of the most important and changing areas of research in paediatric rheumatology is the optimum approach to the treatment of children with chronic arthritis. Until recently all medications for children with arthritis were nonspecific in terms of our understanding, albeit poor, of the pathogenesis of these diseases. Of current therapies, low dose, once-a-week methotrexate has emerged as the therapeutic agent of choice for children who fail to respond adequately to administration of a nonsteroidal anti-inflammatory drug. Thereby, it has displaced the more traditional slower acting anti-rheumatic drugs, although one or more of them are often combined with methotrexate in the polypharmaceutical approach to childhood arthritis. Better and more specific agents are needed, especially for systemic onset disease, unremitting polyarticular involvement, and certain complications such as resistant chronic uveitis. At this time the introduction of the cyclo-oxygenase 2 inhibitors and etanercept (soluble tumour necrosis factoralpha.p75 fusion protein) may herald an era of more specific and effective therapy. | |
| 9153561 | Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of th | 1997 May | This report describes an infant with multiple congenital anomalies born to a 20-year-old mother with juvenile rheumatoid arthritis who had been taking weekly low-dose methotrexate (MTX) during the first trimester of pregnancy. The abnormalities found were consistent with those associated with maternal ingestion of MTX at dosage levels used to induce abortions, i.e., the group of abnormalities referred to as the "aminopterin syndrome." Although weekly low-dose MTX has been associated with spontaneous abortions, this is, to our knowledge, the first case report describing multiple congenital abnormalities consistent with MTX embryopathy secondary to weekly low-dose MTX treatment. | |
| 9218084 | The absorption of low-dose methotrexate in patients with inflammatory bowel disease. | 1997 Jun | BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally. | |
| 11564371 | Recent advances in the treatment of the seronegative spondyloarthropathies. | 2001 Oct | The observation that anti-tumor necrosis factor (anti-TNF) therapies dramatically reduce joint pain and inflammation and retard radiographic progression in rheumatoid arthritis (RA) has created a considerable amount of enthusiasm among rheumatologists and has set new treatment standards for patients with inflammatory joint disease. A central question that has emerged is whether these agents are effective in treating the seronegative spondyloarthropathies (SpA). A related question is whether second-line agents such as methotrexate (MTX) can improve axial inflammation and functional measures if administered early in disease. The SpA are a cluster of inflammatory arthridites encompassing ankylosing spondylitis (AS), psoriatic arthritis (PsA), Reiter's syndrome/reactive arthritis (ReA), and the arthritis associated with inflammatory bowel disease. These disorders share similar clinical and immunogenetic features including axial arthritis and enthesopathy, a general predilection for males and patients positive for the MHC class I alleles, the absence of rheumatoid factor, and association with infections of the intestinal and genitourinary tracts. Reclassification of SpA based on axial or peripheral involvement may be more relevant from a pathophysiologic and therapeutic perspective than the current stratification, given the strong association between axial disease and the HLAB27 allele and the relative resistance of axial disease to conventional anti-inflammatory therapy. | |
| 9598903 | Estimates of the discriminant ability of definitions of improvement for juvenile rheumatoi | 1998 May | OBJECTIVE: To investigate the ability of various definitions of improvement to distinguish between patients with juvenile rheumatoid arthritis (JRA) treated with active drug from those given placebo in randomized trials. METHODS: A core set of 6 response (outcome) variables for use in JRA has been reported. These core variables were combined into a number of "definitions of improvement" for the purpose of classifying individual patients as either "clinically significantly improved" or "not improved." We used a large dataset from randomized controlled trials to test the discriminant ability (sensitivity to change) of the definitions. We calculated the proportion of patients classified as "improved" by each definition in each of the treatment and control groups. RESULTS: Effect sizes were weak in 4 of the treatment regimens used (D-penicillamine, hydroxychloroquine, auranofin, and very low dose methotrexate) and no definition discriminated well between drug and placebo treated groups. Definitions that required 20 to 30% improvement in 3 to 4 of the 6 core set variables showed statistically significant differences in the proportions of patients who were classified as improved in the group treated with low dose methotrexate (10 mg/m2 body surface area/wk) compared to placebo. A definition resembling the Paulus criteria used in adult RA trials (4 of 6 core set variables improved by > or = 20%) performed well, as did the definition selected previously as the best for JRA (3 of 6 core set variables improved by > or = 30%, not more than one worsening by > 30%). CONCLUSION: Definitions that require 20 to 30% improvement in 3 to 4 core outcome variables are sensitive to change and are able to clearly distinguish between treated and control groups when an effective drug is being tested. Further testing of their validity is under way. | |
| 10399226 | [Sandimmun-Neoral--a new quality of life for patients with severe systemic juvenile rheuma | 1999 | AIM: To develop an effective and safe therapeutic policy for Sandimmun-Neoral in order to prevent joint destruction, invalidation, achieve higher life quality in patients with systemic juvenile rheumatoid arthritis (SJRA). MATERIALS AND METHODS: The trial included 26 patients with SJRA aged 4-15 years. 12 of them had early SJRA, 14--late SJRA. 13 patients received Neoral for one year and the other 13 for 2-3.5 years. Markers of aggressive SJRA course in the debut were registered in all the patients. Previous treatment incorporated nonsteroid antiinflammatory drugs, intraarticular corticosteroids (all the patients), prednisolone (19 patients), methotrexate (3 patients). Before Neoral treatment 80% of the patients had structural alterations in the joints, signs of invalidation, low quality of life. SJRA activity was defined as the 3d degree. All the patients suffered from obesity, hypertrichosis, steroid spondylopathy, nanism. RESULTS: Neoral recovered joint motility in 30% of patients, 60% were capable for self-service. Quality of life was assess as high in 80%, moderately reduced--in 20%. 35% of the patients achieved clinico-laboratory remission. The disease activity dropped to degree I-II in 65% of patients. Structural changes in the joints stopped progressing in 77%, regress of the anatomic stage was seen in 20% of patients. Prednisolone was discontinued in 7 and dose-reduced in 6 patients. Exogenic hypercorticism relieved and growth resumed in all the patients. Neoral proved effective both in early and late SJRA, inhibited destruction both in patients in remission and in active disease. Side effects were: hypertrichosis in 13 patients, moderate blood hypertension in 1 case. CONCLUSION: Neoral can control the disease. It is indicated both in early and late SJRA in the presence of aggressive course markers, acute coxitis with aseptic necrosis of the head of the femur or free of it. Neoral treatment should be started as early as on the first year of the disease, before the structural changes in the joints. For safe long-term therapy it is valid to give cyclosporin A in monotherapy or in combination with voltaren in minimal doses. Corticosteroids are used on demand. The preference should be given to intraarticular or intravenous prolonged drugs but not oral prednisolone which may course such severe complications as obesity, hypertension, nanism. | |
| 10328576 | Biologic agents in the treatment of inflammatory rheumatic diseases. | 1999 May | In 1998, further details on the treatment of patients with rheumatoid arthritis with biologic agents became available. Biologic agents with established efficacy, e.g., the chimeric tumor necrosis factor-alpha monoclonal antibody cA2, were tested in combination with methotrexate (MTX), with evidence of synergistic effects. These trials revealed new, important information on the incorporation of tumor necrosis factor-alpha blocking agents into a treatment regimen of rheumatoid arthritis using established disease-modifying antirheumatic drugs and innovative biologic agents. Clinical trials testing new agents, e.g., T-cell receptor peptides in a double-blind, placebo-controlled fashion represented new developments with regard to T cell-directed treatment principles. In addition, new developments in the preclinical phase are discussed. | |
| 10615829 | One year in an Alaskan arthritis clinic. | 1999 Oct | During 1997 visits were made by 852 individuals to an arthritis clinic in Alaska serving predominantly Alaska Natives. Three hundred twenty- seven of these were seen for the first time. The ratio of women to men was 3:1. Rheumatoid Arthritis was the most common arthritic condition seen, followed by Degenerative Joint Disease and Spondyloarthropathies. Three hundred five Tlingit and 246 Eskimo made up 65% of the patients seen that year. Methotrexate was the most frequently used Disease Modifying Antirheumatic Drug but the other such drugs were prescribed as well. Recording demographic and clinical information on a portable computer at the time of visit provided record linkage and the data for this report and was used in Health Care Planning. | |
| 10492146 | Severe hepatitis and pure red cell aplasia in adult Still's disease: good response to immu | 1999 Aug | Adult-onset Still's disease is a systemic inflammatory disorder with a highly variable clinical course. Mild hepatitis and anemia are common manifestations. We describe a patient with adult Still's disease who developed a severe hepatitis and a life-threatening pure red cell aplasia. The hepatitis developed after treatment with NSAIDs was started. The patient was successfully treated with a combination of prednisone, cyclosporin, and methotrexate. Physicians should be aware that severe hepatitis and pure red cell aplasia can occur in adult Still's disease. We recommend a careful monitoring of liver functions in patients with adult Still's disease who are being treated with NSAIDs. | |
| 19078220 | Inhibition of methotrexate-induced rheumatoid nodulosis by colchicine: evidence from an in | 1997 Dec | Methotrexate is one of the most effective and widely used medications in the treatment of rheumatoid arthritis. One poorly understood side effect of methotrexate is increased rheumatoid nodule formation, a phenomenon which has been reported to occur in some patients despite suppression of synovial inflammation. Using an in vitro model of nodulosis, induction of monocyte differentiation into multinucleated giant cells, we previously found that methotrexate promotes this inflammatory response by a mechanism dependent on adenosine A1 receptor stimulation. In the current study, we tested the effects of an A1 signal inhibitor, the commonly available anti-inflammatory medication colchicine, and found that it markedly inhibited nodulosis in vitro as well as in seven of fourteen patients in a clinical series. | |
| 10028378 | Age-depending effects of methotrexate treatment on systemic bone turnover in experimental | 1999 Jan | Adjuvant arthritis was induced in rats in the growth stage (aged 6 weeks) and those in the mature stage (aged 4 months), and changes in the systemic bone turnover and the effects of methotrexate (MTX, CAS 133073-73-1) were compared. After induction of adjuvant arthritis, the paw edema ratio and the urinary deoxypyridinoline (u-Dpy) level increased in both age groups. No marked changes were observed in the serum osteocalcin (s-OC) level in either group. In the 6-week-old rats, arthritis completely inhibited the bone mass, and strength of the femur and lumbar vertebral body. The 4-month-old rats showed more marked changes than the 6-week-old rats in the bone mass and strength of the lumbar, vertebral body. MTX administration (0.05, 0.1 and 0.2 mg/kg/day) resulted in significant dose-dependent inhibition of arthritis-induced changes, and the effects of MTX were similar between the two age groups. MTX was useful at each age. These results suggest that 4-month-old rats with arthritis are more appropriate as a model for evaluation of drugs for bone metabolic turnover in human chronic rheumatoid arthritis. | |
| 17984889 | Rheumatological considerations in the qualification of rheumatoid patients for surgical tr | 2000 Dec 30 | The surgical treatment of rheumatoid arthritis patients can be safe because it is planned treatment, but it requires the close cooperation of the orthopedic surgeon, the rheumatologist, and the anesthesiologist. The proper evaluation of the risk factors for coexisting diseases decreases the possibility of general surgical and infectious complications. Thromboembolic preventive measures after surgery are an absolute requirement, for at least 15 days after the operation, using heparin of low molecular weight; preventive antibiotic therapy is also required, using second-generation cephalosporing for 3-5 days, depending on the risk factors. Methotrexate treatment should be suspended for 7 days during the peri-operative period. Prolonged steroid therapy creates a risk of adrenal failure in the event of illness or peri-operative stress, which increases with the steroid dosage and the prolongation of therapy. Steroid administration cannot be stopped prior to surgery. Treatment outcome depends on the activity level the disease and the skill of the surgeon, as well as pre- and post-operative care and rehabilitation. | |
| 11102777 | Novel, non-antigen-specific therapeutic approaches to autoimmune/inflammatory diseases. | 2000 Dec | Anti-TNF therapy has made a major impact on the treatment of inflammatory arthritides and Crohn's disease. It leads to prompt and prolonged clinical response, even in patients refractory to conventional therapy. Moreover, the progression of joint damage noted in patients with rheumatoid arthritis treated with methotrexate was prevented by an anti-TNF-alpha antibody, suggesting a genuine disease-modifying potential of TNF-alpha blockade. | |
| 19078423 | The effect of methotrexate on the temporomandibular joint in polyarticular juvenile rheuma | 1999 Dec | Temporomandibular joint (TMJ) arthropathy is common in juvenile rehumatoid arthritis (JRA) patients and can cause functional and esthetic problems. The purpose of this pilot study was to begin to evaluate whether methotrexate (MTX) therapy can reduce TMJ arthropathy in patients with polyarticular JRA.There were 27 patients with polyarticular JRA studied. Of these, 18 were receiving MTX and non-steroidal anti-inflammatory drugs and 9 were receiving just non-steroidal anti-inflammatory drugs. A routine physical examination, including a detailed joint evaluation, was performed by their rheumatologist. A craniofacial examination was performed by the orthodontist and included a radiographic TMJ evaluation (panoral and corrected axial tomograms).Radiographic evidence of condylar degeneration was apparent in 83% of all polyarticular JRA patients. The patients receiving MTX showed less severe TMJ involvement than those not receiving MTX. |