Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 11147769 | Combination therapy with hydroxychloroquine, gold sodium thiomalate and methotrexate in ea | 2000 | During recent years, aggressive therapeutic approaches have been proposed in order to control the Rheumatoid Arthritis (RA) activity and to avoid joint destruction. Here we report the results of an open 3-year trial on the combination of three second-line drugs, hydroxychloroquine (HCQ), methotrexate (MTX) and gold sodium thiomalate (GST), in early active RA. Four men and 17 women were enrolled in the study and were treated during the first year with HCQ 400 mg/day, GST 50 mg/week and oral MTX 7.5 mg/week; during the second and the third years the doses of HCQ and MTX were reduced to 200 mg/day and 5 mg/week, respectively; the interval between the GST injections was progressively increased until 4 weeks. Prednisone at an initial dose not higher than 10 mg/day was associated. Sulindac was allowed. Eight patients left the study because of side-effects, 2 patients abandoned the study, 12 patients compleated the 3 years of treatment. We obtained a significant and early amelioration of both clinical and laboratory parameters during the first year; in the two subsequent years the positive results were maintained. In our opinion the most significant result is the absence of anatomical progression in 10 out of 12 patients, even if a more prolonged observation is necessary to obtain more reliable data. | |
| 10774461 | Anti-cytokine therapy for rheumatoid arthritis. | 2000 | Tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) are important in mediating inflammation in rheumatoid arthritis (RA). Randomized phase II and III clinical trials of anti-TNF reagents (infliximab and etanercept) have demonstrated an acceptable safety profile and marked clinical efficacy in cases of RA that have not responded adequately to conventional therapy. Combination therapy with methotrexate (MTX) appears to be particularly effective in patients whose disease activity persists despite prior disease-modifying antirheumatic drugs (DMARDs) and ongoing MTX monotherapy. DMARD-recalcitrant disease may become the main indication for the use of anti-TNF drugs in patients with RA. Trials of IL-1 receptor antagonist show a relatively modest anti-inflammatory effect and a possible retardation of joint damage. Whether anti-TNF therapy protects joints from structural damage is under investigation. One anti-TNF reagent has already been approved in the United States for the treatment of RA, and other cytokine antagonists or agonists are under development. | |
| 9128419 | [Toxicity of low-dose methotrexate in rheumatoid arthritis--clinical characteristics in pa | 1997 Feb | Pancytopenia and interstitial pneumonitis are one of the most serious and unpredictable adverse effects of low dose, pulse methotrexate (MTX) in treating rheumatoid arthritis (RA). It is important to investigate the historical, clinical or immunologic features associated with the development of such toxicity, in order to use MTX more appropriately. Two hundred eighty four patients (female 230 male 54) with rheumatoid arthritis had been treated with pulse weekly oral MTX with a mean follow-up of 33.2 months. Adverse effects which required the discontinuation of MTX occurred in 47 patients (16.5%). Gastrointestinal toxicity occurred most frequently (14 patients) and liver dysfunction occurred in 9 patients. Four patients (1.4%) developed pancytopenia, and six patients (2.1%) developed interstitial pneumonitis. All patients who developed pancytopenia were old female with long history of active, deforming rheumatoid arthritis, The cumulative dose of MTX ranged from 15 mg to 760 mg at the time pancytopenia developed. Impaired renal function, hypoalbuminemia, and multiple medication were observed, and antinuclear antibodies were positive in most patients. It should be noted that severe stomatitis preceded or accompanied with pancytopenia in all patients. Blood counts returned to the normal level in 7 to 14 days. All patients who developed interstitial pneumonitis were old female. The cumulative dose ranged from 65 mg to 580 mg. Pre-existance of lung diseases, history of adverse effects of other DMARDs, the presence of Raynaud's phenomenon, and antinuclear antibodies appeared to be risk factors for interstitial pneumonitis. All patients recovered with high dose of corticosteroid and mechanical ventilation. Such clinical characteristics that are associated with MTX-induced pancytopenia or interstitial pneumonitis should be reminded in the treatment of rheumatoid arthritis with MTX. | |
| 9734684 | Methotrexate treatment in Felty's syndrome. | 1998 Aug | Felty's syndrome is a rare disorder characterized as a systemic manifestation of severe rheumatoid arthritis associated with granulocytopenia and splenomegaly. We report a retrospective analysis of a series of seven patients treated successfully with low-dose methotrexate. leading to sustained clinical improvement (number of swollen joints) and normalization of the granulocyte count for an observation period of 1 yr. Our cohort is the largest ever published with methotrexate treatment of this rare condition. Our results confirm earlier single case reports suggesting methotrexate to be the first-choice treatment nowadays in Felty's syndrome. | |
| 9231507 | [Pharmacokinetics of methotrexate in rheumatoid arthritis: therapeutic implications]. | 1997 Mar | The fraction of oral methotrexate (MTX) absorbed averages 70 per cent at low doses (< or = 10 mg/m2), both fasting and after food. The mean binding of MTX to serum albumin is 42-57 per cent. Less than 10 per cent of MTX is oxidised to 7-OH-MTX. Furthermore, MTX is partly converted to polyglutamate derivatives which accumulate in some cells resulting in sustained efficacy of the drug in spite of its relatively short plasma elimination half-life. MTX is mainly excreted by the kidney as intact drug. Accordingly careful monitoring of renal function is justified. MTX undergoes bidirectional transport within the renal tubules leading to drug interactions. Oral, intramuscular and subcutaneous routes of administration were reported to result in comparable bioavailability. There is a marked interindividual variability in MTX disposition. Conversely, the intraindividual variability is moderate even over a long time period. Finally, no clear relationship between pharmacokinetic parameters and clinical response or toxicity has been found in patients with rheumatoid arthritis. | |
| 14635276 | Medical resource use and costs among rheumatoid arthritis patients receiving disease-modif | 2000 Aug | OBJECTIVE: To identify costs among rheumatoid arthritis (RA) patients receiving alternative disease-modifying antirheumatic drug (DMARD) therapies. METHODS: Using managed care organization data, we identified members who (a) were prescribed any DMARD therapy for two consecutive months between July 1993 and February 1998, (b) were aged > or = 18 years, (c) had > or = 6 months of DMARD-free enrollment prior to the first DMARD, and (d) had a diagnosis of RA. RESULTS: The average age of the cohort (n = 571) was 51 years, and 70% were women. Mean duration of enrollment following initiation of DMARD therapy (observation period) was 19.5 months; 28.8% of patients switched DMARD regimens. The average monthly cost of care was $853, of which $294 (34%) was for RA-coded medical services. Monthly RA-coded costs varied by DMARD: hydroxychloroquine $227 (n = 252), methotrexate $340 (n = 185); sulfasalazine $233 (n = 49), and other mono/combination therapy $425 (n = 85) (P = 0.001). CONCLUSION: Costs of RA-coded care in patients receiving DMARDs are low and vary by DMARD. | |
| 9852750 | [Hemophagocytic syndrome in a patient with rheumatoid arthritis]. | 1998 Oct | A 62-year-old man with 16 year-history of rheumatoid arthritis (RA) was admitted due to progressive pancytopenia, general fatigue, and high fever. He was treated with 5 mg methotrexate weekly in RA. His bone marrow examination revealed a decreased nuclear cell count (2.1 x 10(4)/microliter), megakaryocyte count (16/microliter), and macrophages phagocytizing blood cells (13.2%), indicating the presence of hemophagocytic syndrome. No infections agent was detected in cultures derived from his blood or other sources. The serological tests for several viruses revealed no obvious viral etiology. The systemic lymphonodes were not swelling. Administration of 40 mg prednisolone daily improved his abnormal hematological findings. This is a case of RA accompanied by hemophagocytic syndrome, which is a rare complication of RA. | |
| 11502618 | Lymphoma in a patient with rheumatoid arthritis receiving methotrexate treatment: successf | 2001 Sep | A 55 year old man with chronic lymphocytic leukaemia (CLL) and rheumatoid arthritis (RA), treated for four years with methotrexate (MTX), who developed a B cell non-Hodgkin's lymphoma (B-NHL), is described. The tumour was localised to the shoulder and axillary lymph nodes, and positive for Epstein-Barr viral antigens. After failure of radiation and chemotherapy, a complete remission was achieved with a combination of antibody treatment (rituximab) and EPOCH. The development of a second malignancy in a patient with RA receiving MTX has not been described before. The summation of T cell deficiencies induced by MTX, CLL, and RA may all have contributed to the development of the B-NHL. | |
| 9125255 | Abnormal homocysteine metabolism in rheumatoid arthritis. | 1997 Apr | OBJECTIVE: To assess total homocysteine (tHcy) metabolism in patients with rheumatoid arthritis (RA). METHODS: Assessments were performed to determine the fasting levels of tHcy and the increase in tHcy in response to methionine (Met) challenge in blood samples from 28 patients with RA and 20 healthy age-matched control subjects. RESULTS: Fasting levels of tHcy were 33% higher in the RA patients than in the control subjects (mean +/- SD 11.7 +/- 1.5 nmoles/ml versus 8.8 +/- 1.1 nmoles/ml; P < 0.01). Four hours after Met challenge, the increase in plasma tHcy levels (delta tHcy) was higher in the RA patients (20.9 +/- 10.4 nmoles/ml) than in the control subjects (15.5 +/- 1.6 nmoles/ml) (P < 0.02). In a subgroup analysis, the delta tHcy in patients taking methotrexate (12.9 +/- 2.2 nmoles/ml) did not differ from that in the control group, while the delta tHcy in patients not taking methotrexate (25.3 +/- 1.7 nmoles/ml) was significantly higher (P < 0.0001). CONCLUSION: Elevated tHcy levels occur commonly in patients with RA, and may explain some of the increased cardiovascular mortality seen in such patients. Studies of the prevalence and mechanism of hyperhomocysteinemia in RA are warranted. | |
| 9352604 | Radiosynoviorthesis with rhenium-186 in rheumatoid arthritis: a prospective study of three | 1997 | The aim of this study was to evaluate the efficiency of radiation synovectomy with rhenium-186 in rheumatoid arthritis. In this prospective, randomized trial we compared three different treatment regimens for shoulder, elbow, wrist, hip and ankle joints: group 1, injection of rhenium-186; group 2, injection of rhenium-186 in combination with triamcinolone hexacetonide; group 3, injection of triamcinolone hexacetonide alone. Each treatment group included 50 joints. Patients included in the study had to fulfil the following criteria: (1) they had to have a diagnosis of rheumatoid arthritis (ARA criteria 1988), (2) their disease-modifying drug had to be methotrexate, started at least 6 months prior to injection therapy and given for the entire study time, (3) their nonsteroidal anti-inflammatory drug had to be diclofenac given at a dose of 150 mg/day or less and (4) they were also given prednisolone at a dose of 7.5 mg/day or less. After 3 years of follow-up, 79 joints met these criteria, i.e. 71 joints were excluded from the study: 26 joints because the patients changed the disease-modifying drug (12 joints from group 1, 4 joints from group 2 and 10 joints from group 3); 45 joints because of recurrent synovitis and second-stage treatment (21 joints from group 1, 5 joints from group 2 and 19 joints from group 3). During the follow-up period, joints were assessed for pain, synovitis, joint motion and stage of radiological destruction. Best clinical results and slowest progression in radiological destruction were achieved with the combined injection of rhenium-186 and triamcinolone hexacetonide. Therefore, we recommend this treatment for articulosynovitis with the exception of severe forms, the latter because of the effective penetration range of rhenium-186. | |
| 11060753 | Biological agents: a novel approach to the therapy of rheumatoid arthritis. | 2000 Jul | Rheumatoid arthritis (RA) is the most common chronic autoimmunopathy, clinically leading to joint destruction as a consequence of the chronic inflammatory processes. The pathogenesis of this disabling disease is not well understood, but molecular events leading to tissue inflammation with cartilage and bone destruction are now defined in more detail. Established therapy, slow acting disease-modifying antirheumatic drugs (DMARDs) as with low-dose methotrexate (MTX) are the accepted 'golden standard' therapies and both lead to a significant improvement of disease symptoms, however are unable to stop joint destruction. Due to these disappointing treatment options and the identification of some inflammatory mediators as therapeutic targets, novel therapeutic agents such as monoclonal antibodies (mAbs), cytokine receptor-human immunoglobulin constructs or recombinant human proteins have been tested in RA with some success. In particular, clinical trials testing anti-TNF-alpha agents either alone or in combination with MTX have convincingly demonstrated the feasibility and efficacy of these novel approaches to the therapy of RA. Importantly, a clinical trial testing combination therapy with chimeric (mouse-human) anti-TNF-alpha mAb cA2 (Remicadetrade mark) and MTX could, for the first time in any RA trial, show that average radiological progression in the cA2/MTX groups could be completely prevented over a 12 month observation period. Similar encouraging results might evoke from trials employing other TNF-alpha-directed agents like the fully human mAb D(2)E7 or the p75 TNF-alpha-receptor-Ig construct, etanercept. | |
| 9825750 | Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: | 1998 Oct | OBJECTIVE: Assessment of the cost-effectiveness and cost-utility of early intervention in rheumatoid arthritis (RA) patients, with combined step-down prednisolone, methotrexate and sulphasalazine, compared to sulphasalazine alone. METHODS: Multicentre 56 week randomized double-blind trial with full economic analysis of direct costs and utility analysis with rating scale and standard gamble measurement techniques. RESULTS: The combined-treatment group included 76 patients and the sulphasalazine group 78 patients. The mean total costs per patient in the first 56 weeks of follow-up were $5519 for combined treatment and $6511 for treatment with sulphasalazine alone (P = 0.37). Out-patient care, in-patient care and non-health care each contributed about one-third to the total costs. The combined-treatment group appeared to generate savings in the length of hospital stay for RA, non-protocol drugs and costs of home help, but comparisons were not statistically significant. Protocol drugs and monitoring were slightly more expensive in the combined-treatment group. Clinical, radiographic and functional outcomes significantly favoured combined treatment at week 28 (radiography also at week 56). Utility scores also favoured combined treatment. CONCLUSION: Combined treatment is cost-effective due to enhanced efficacy at lower or equal direct costs. | |
| 9361159 | Methotrexate use in miscellaneous inflammatory diseases. | 1997 Nov | Methotrexate has proven to be a safe, effective, long-term therapy for rheumatoid arthritis. Its property as a corticosteroid-sparing drug in rheumatoid arthritis has been recognized and its potential has been explored in other inflammatory and autoimmune diseases. This article describes and analyzes the use of methotrexate for a wide variety of diseases, some of which are not the usual province of rheumatologists, to provide some guidance concerning its role for treatment. Methotrexate therapy seems promising for systemic lupus erythematosus, inflammatory myopathy, inflammatory eye disease, inflammatory bowel disease, and some manifestations of sarcoidosis. Its role in other diseases is not as well defined. | |
| 9517760 | Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia | 1998 Mar | OBJECTIVE: To determine the effect of longterm methotrexate (MTX) therapy and folic acid supplementation on folate nutriture and homocysteine levels in patients with rheumatoid arthritis. METHODS: A double blind, placebo controlled trial lasting one year was conducted at one academic medical center. A total of 79 patients taking low dose MTX were followed up to one year. The patients were randomized to receive placebo or 5 or 27.5 mg folic acid supplementation per week. RESULTS: Plasma and erythrocyte folate levels and plasma homocysteine levels were determined. The folate nutriture of patients taking low dose MTX declined without folic acid supplementation. Plasma homocysteine levels increased significantly over a one year period in the placebo group. Low folate nutriture and hyperhomocysteinemia occurred with greater frequency in the placebo group than in the folic acid supplemented groups. CONCLUSION: For longterm, low dose MTX therapy, there are now at least 3 reasons to consider supplementation with folic acid (a low cost prescription): (1) to prevent MTX toxicity, (2) to prevent or treat folate deficiency, and (3) to prevent hyperhomocysteinemia, considered by many investigators to be a risk factor for cardiovascular disease. | |
| 9150069 | Response to therapy in rheumatoid arthritis is influenced by immediately prior therapy. | 1997 May | OBJECTIVE: Clinicians do not often employ washout periods before prescribing a change in therapy for rheumatoid arthritis (RA). As a result, the observed effectiveness or lack of effectiveness of a new drug actually represents the effectiveness of that drug had the patient been taking placebo minus the residual effectiveness of the old drug. METHODS: We studied new starts of selected disease modifying antirheumatic drugs (DMARD) and prednisone in 2,898 patients with RA from 8 ARAMIS data bank centers, broken into subgroups on the basis of immediately prior therapy. Therefore, we examined the hypothesis that the chances of a treatment being observed effective depend upon the immediately preceding treatment. Using intent-to-treat analysis, we analyzed the effects upon Health Assessment Questionnaire (HAQ) disability and pain scores an average of 9 months after the new drug start. RESULTS: Methotrexate reduced disability significantly except after intramuscular gold or hydroxychloroquine and it reduced pain significantly after all prior therapies. Hydroxychloroquine reduced disability significantly after nonsteroidal antiinflammatory drugs (NSAID) only, but disability increased after intramuscular gold; pain was decreased only after NSAID only. Prednisone had no consistent effect upon disability but was consistently associated with decreased pain. Greatest effectiveness was always seen with a new drug start after NSAID only treatment versus after DMARD treatment. CONCLUSION: The effectiveness of a newly started RA treatment after 9 months may be substantially influenced by immediately prior treatment. This finding provides an additional reason for concern about direct extrapolation of clinical trial data into clinical practice. | |
| 10063319 | A case of pancytopenia secondary to low-dose pulse methotrexate therapy in a patient with | 1999 Jan | Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized. We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency. A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993. Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment. This was begun as a single oral dose of 5mg/week. After 2 doses, the patient was admitted to the hospital with general weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal, but the serum albumin level was 2.7 g/dl. The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and intravenous prophylactic antibiotic therapy were required. Her condition was improved. In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency. Close monitoring of associated risk factors, particularly impaired renal function, should be mandatory for all patients who are receiving MTX therapy. | |
| 9117183 | Why intramuscular methotrexate may be more efficacious than oral dosing in patients with r | 1997 Jan | In order to compare the relative bioavailability of orally administered methotrexate (MTX) with i.m. administration in patients with rheumatoid arthritis, we compared the pharmacokinetics of MTX at both the usual starting dose of 7.5 mg and at higher established maintenance dosages in 21 patients. Pharmacokinetic measures were repeated approximately 6 and 18 months after baseline while patients consumed their usual maintenance doses of MTX (17.0 +/- 3.8 mg). The relative bioavailability of the usual maintenance dose of MTX was reduced by 13.5% compared with the initial dose of 7.5 mg (P = 0.026). Area under the serum concentration vs time curve (AUC) was significantly reduced with oral vs i.m. administration at usual maintenance doses (decrease of 0.729 mumol.h/l by oral administration, P = 0.027), but not at a 7.5 mg dose of MTX. Clinicians using MTX should not assume constant and complete bioavailability across the dose range used to treat patients with rheumatoid arthritis. Our observations explain the reported clinical success of switching from an oral to a parenteral route of administration in patients receiving maintenance doses of MTX. | |
| 9778226 | Validation of rheumatoid arthritis improvement criteria that include simplified joint coun | 1998 Oct | OBJECTIVE: To study the validity of response criteria for rheumatoid arthritis (RA) that included 28-joint counts instead of more comprehensive joint counts. METHODS: In a double-blind, placebo-controlled trial of 105 patients treated with methotrexate, sulfasalazine, or both, response was evaluated at week 52. Both European League Against Rheumatism and American College of Rheumatology definitions of response, with comprehensive as well as simplified joint counts, were calculated. We studied the differences between the criteria with and without simplified joint counts, the discriminating capacity between treatment groups, and the association with change in functional capacity and joint damage. RESULTS: Response criteria that included 28-joint counts classified patients' responses more conservatively. No differences between treatment groups were found with either set of response criteria. The association with change in functional capacity was significant in all cases. All response criteria were significantly associated with radiographic progression of RA. CONCLUSION: Improvement criteria that include 28-joint counts are as valid as the original improvement criteria that included more comprehensive joint counts. | |
| 9008613 | Methotrexate-associated appearance and rapid progression of rheumatoid nodules in systemic | 1997 Jan | Rheumatoid nodules are a rare extraarticular manifestation of juvenile rheumatoid arthritis (JRA), usually detected in patients with polyarticular-onset disease and positive rheumatoid factor (RF). To date, there has not been a published report of rheumatoid nodules in systemic-onset JRA. Low-dose methotrexate (MTX) is generally considered to be the most useful second-line drug in the treatment of polyarticular JRA. In adult RA, MTX has been shown to be associated with appearance and progression of rheumatoid nodules. This report describes a 3-year-old girl with RF-negative, antinuclear antibody-negative systemic JRA who developed multiple rheumatoid nodules on the scalp and trunk during MTX therapy. The first nodule developed on the scalp 6 months after MTX treatment was initiated. Previous treatment with azathioprine was not associated with nodulosis. This represents an atypical case of MTX-associated accelerated nodulosis in systemic JRA, and raises the problem of treatment plan modification in the presence of this side effect. | |
| 10589356 | Methotrexate and emerging therapies. | 1999 Nov | More publications in the medical literature have described the clinical efficacy and toxicity of methotrexate (MTX) than of any other drug ever used for rheumatic diseases. A knowledgeable clinical can thus rely on evidence-based medicine to guide the use of this agent. Because MTX is not remission-inducing, many new therapies are being combined with it in order to achieve a greater therapeutic response. This trend will likely continue and expand as more novel agents are introduced. |