Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8608361 | Folate supplementation and methotrexate. | 1995 Dec | This review concentrates on the influence of folate supplementation on the toxicity and efficacy of methotrexate (MTX) in rheumatoid arthritis patients. The design, type of folate supplementation and timing of supplementation vary considerably between the six published controlled studies. Folate supplementation seems to have no effect on the efficacy of MTX but may influence toxicity in a favourable way. Further studies are needed to assess the type of supplementation (folic acid, folinic acid), the predisposing factors for toxicity and cost effectiveness. | |
| 8556805 | Methotrexate in rheumatoid arthritis: when NSAIDs fail. | 1995 Nov | Methotrexate has become the agent of choice for rheumatoid arthritis that does not respond to nonsteroidal anti-inflammatory drugs. In appropriately selected patients and with diligent monitoring, methotrexate in low weekly doses is effective and has a much better safety profile than was originally perceived. | |
| 8574610 | Pancytopenia and severe cytopenia induced by low-dose methotrexate. Eight case-reports and | 1995 Jul | Severe adverse effects of low-dose methotrexate (less than 20 mg per week) are believed to be rare. We report eight cases of severe tricytopenia or pancytopenia seen in two medical departments of the same hospital in patients receiving low-dose methotrexate. Three patients had been under methotrexate for less than one month. Of the six patients with joint disease, five had rheumatoid arthritis and one psoriatic arthritis. A review of the literature found 92 previously reported cases of severe tricytopenia or pancytopenia induced by low-dose methotrexate. Of the total of 100 cases, 24 were fatal and 25 occurred within one month of treatment initiation. Potential risk factors were identifiable retrospectively in at least 50% of cases but were not all predictable or present at treatment initiation. In 30% of cases, no explanation for the hematologic complication was found, and in an additional 20% missing data precluded definite conclusions. The role of the risk factors incriminated in the literature is discussed. Although infrequent, cytopenia is a severe complication of methotrexate therapy that warrants a number of precautions, including periodic creatinine clearance and serum albumin determinations. Furthermore, the weekly dosing schedule should be printed on methotrexate boxes. | |
| 8032050 | Invasive pulmonary aspergillosis associated with low dose methotrexate therapy for rheumat | 1994 Apr | Opportunistic infections complicating low dose methotrexate therapy are rare, consisting predominantly of Pneumocystis carinii pneumonia. We report a case of invasive pulmonary aspergillosis which developed in a patient being treated for seropositive rheumatoid arthritis with low dose methotrexate (5-7.5 mg weekly) for 8 years. The patient was successfully treated with itraconazole 200 mg daily for 6 months. This case adds to the growing evidence implicating low dose methotrexate with opportunistic infections and should heighten clinical awareness in patients on this treatment. | |
| 1355956 | [Salazosulfapyridine in rheumatoid arthritis. A study of 49 patients]. | 1992 | The results of an open retrospective study of 49 patients treated with salazosulfapyridine (SASP) (sulphasalazine) for rheumatoid arthritis (RA) are reported. The patients, 7 men and 42 women, had a mean age of 53 years, and their mean duration of evolution of RA was 13.3 years. Sixty percent of them had undergone more than 3 previous disease-modifying drugs. The mean length of SASP treatment was 15.3 months. The initial response was favorable in 34 patients (69%). Treatment was ineffective and stopped in 12 cases (24.5%); the inefficacy was primary in 6 and tachyphylactic in the other 6. Twenty patients (41%) experienced at least one side effect. SASP was stopped in 11 patients (20.4%) due to undesirable side effects; 9 of the 11 times were during the first 2 months of treatment. Digestive system intolerance was the most common but led to drug withdrawal in less than half the patients. In all cases, mucocutaneous, neurosensory, hematological and hepatic side effects regressed during the month following SASP withdrawal. The therapeutic maintenance level was 67% at 1 year, 60% at 18 months, 52% at 2 years and 45% at 3 years. SASP has a role in the treatment of relatively slightly evolved forms of RA, before prescribing methotrexate. The possibility of delayed intolerance reactions, notably hematological and hepatic, justify prolonged biological monitoring of these patients. | |
| 7482065 | [A case of rheumatoid arthritis with malignant lymphoma taking methotrexate]. | 1995 Aug | We describe one case with rheumatoid arthritis who developed non-Hodgkin's lymphoma during treatment with low dose weekly methotrexate. A 73 year-old man had seropositive RA since 1974. He had been treated with several medications, including nonsteroidal antiinflammatory drugs, gold sodium thiomalate (from January, 1987), and bucillamine (from January, 1988). He presented to this hospital in April 1988, at a time when his rheumatoid arthritis worsened. Methotrexate was administered at a weekly dose of 7.5 mg orally, together with a daily dose of 5 mg of prednisone. He had had no joint-related pain and no side effects until December 1991 (total dose 1290 mg) when severe abdominal pain was started abruptly. The chest X-ray showed an abdominal free air and a diagnosis of acute panperitonitis was made. An emergency operation was carried out. There was a soft-tissue mass in the terminal of ileum which was ruptured with massive ascites. Histologic examination of the mass revealed a diffuse large cell lymphoma. The oncogenic potential of MTX and rheumatoid arthritis is reviewed. | |
| 1618601 | Strategies for the development of new antiarthritic agents. | 1992 Apr | Therapeutic advances in rheumatoid arthritis (RA) have largely focused on the development of non-steroidal antiinflammatory drugs (NSAIDs) with improved characteristics compared with aspirin [Brooks & Day, New Engl. J. Med., 324, 1716-1725 (1991)]. For example, greater potency, safety, improved tolerance in the elderly and reduced frequency of dosing have been achieved. However, these agents are generally considered to be palliative treating of the symptoms of the disease. The development of disease modifying drugs (DMD), also known as second line drugs, for RA has not been very successful. Most of the agents that are currently used in this category were originally used to treat other diseases such as malignancy (cyclophosphamide, methotrexate), Wilson's disease (d-penicillamine) and tuberculosis (gold salts) [Pullar, Br. J. clin. Pharmac., 30, 501-510 (1990)]. Unfortunately, none of the agents is ideal and each has potentially serious side-effects. There have been several attempts to develop agents with new mechanisms of action that hopefully will greatly improve these current therapies. | |
| 7921763 | Cirrhosis in patients with rheumatoid arthritis receiving low dose methotrexate. | 1994 Oct | We describe three patients with RA who developed cirrhosis while taking low dose methotrexate (MTX). This report includes a review of the risk factors for cirrhosis occurring in association with MTX. Two of these patients were part of a prospective study to quantify changes in pericellular and total collagen in 76 patients with RA receiving low dose pulse MTX, giving a point prevalence of cirrhosis of 2.63%. | |
| 8235288 | Long-term experience with low dose methotrexate in rheumatoid arthritis. | 1993 | One hundred twenty-six patients with rheumatoid arthritis (RA) were treated with weekly low doses of methotrexate (MTX) for a mean period of 36.8 months (range 13-110 months). The overall probability of continuing with MTX therapy was 72% at 2 and 3 years, 67% at 4 years and 65% at 5-7 years. Seronegative patients had a higher probability of continuing therapy than seropositive patients (P < 0.05). Out of the whole group, 8% showed no improvement, 16% showed mild improvement, 30% showed moderate improvement, and 45% experienced marked improvement. Eight patients (6%) of the latter group achieved complete clinical remission. In the course of the follow-up period there was a significant decrease in the mean daily dosage of prednisone and NSAIDs. Minor side effects were common (68%), but therapy was discontinued in only 27 patients (21%) because of major complications. In most of them (25 out of 27) these occurred within the first 24 months of therapy. Although malignancy was revealed in 5 patients during the follow-up period, its occurrence did not differ from expected rates. | |
| 8591645 | The epidemiology of drug treatment failure in rheumatoid arthritis. | 1995 Nov | The length of time that patients remain on anti-rheumatic therapy is an important measure of the effectiveness of that therapy since length of time on therapy is a composite measure that accounts for sustained, positive therapeutic benefit as well as negative therapeutic benefit (e.g. adverse reactions, unacceptable costs and loss of efficacy), and accounts for noise (non-compliance, psychological factors, misunderstanding, etc.). Effectiveness is a measure of how well a drug does work, while efficacy, the measure used in randomized controlled trials, means that a drug can work; however, efficacy may or may not translate to usefulness in the clinic. To understand drug effectiveness we reviewed studies of 5809 patients receiving various SMARDs. The average median time on drug ranged from 1.10 to 2.27 years, excluding methotrexate, with shortest survival times falling to sulfasalazine (1.10) and auranofin (1.16), intermediate times to hydroxychloroquine (1.59), penicillamine (1.42), IM gold (1.40), and the longest time to azathioprine (2.27). Overall, excluding methotrexate, the average median survival time was 1.41 for 3998 patients. Median time on drug was 3.3 times greater for all other drugs combined, averaging 4.61 years. Expressed in terms of '5-year survival,' an average of 55.7% of patients remained on methotrexate 5 years after it was started. Better results noted here for methotrexate stand in contradistinction to short-term randomized controlled trials which find most SMARDs to be equal in efficacy. Other factors that may influence drug survival time include age, age, education level, psychological status, presence of fibromyalgia, rank order of SMARD administration, disease severity or corticosteroid administration. Studies can provide more information if they also measure clinical variables as well as time on drug, providing area-under-the-curve measurements. | |
| 7482340 | [The combined intensive therapy of rheumatoid arthritis with systemic manifestations]. | 1995 | The efficacy of pulse therapy in combination with hemosorption or plasmapheresis, pulse therapy without extracorporeal treatment and methotrexate has been compared for 40 patients with rheumatoid arthritis (RA) with extra-articular manifestations. All kinds of intensive treatment were effective. Extracorporeal methods and pulse therapy relieved extra-articular symptoms. Isolated pulse therapy alleviated articular syndrome. The best results were obtained in double filtration of plasma in combination with pulse therapy. Such approach ensured improvement both articular and extra-articular inflammation. Combined intensive therapy proved an effective modality in RA able to produce responses in severe disease. | |
| 1433017 | Association of methotrexate, rheumatoid arthritis and lymphoma: report of 2 cases and lite | 1992 Sep | We describe 2 Caucasian men with rheumatoid arthritis (RA) who developed non-Hodgkin's lymphoma of identical histological type during treatment with low dose oral weekly methotrexate (MTX). Both patients had longstanding RA and had been treated with MTX for over 2 years at time of tumor diagnosis; neither had secondary Sjögren's syndrome. The oncogenic potential of MTX and RA arthritis is reviewed. | |
| 8971280 | Review article: methotrexate in gastroenterology--dangerous villain or simply misunderstoo | 1996 Dec | Methotrexate has a place in the treatment of an increasing number of diseases. Its emerging role in the treatment of primary biliary cirrhosis and inflammatory bowel disease still requires further evaluation. Its toxicity profile is wide and is affected by a variety of factors. Hepatotoxicity from long-term use in patients with psoriasis and rheumatoid arthritis holds particular concern for the physician. Appropriate monitoring guidelines for hepatotoxicity can only be made after careful evaluation of available data and consideration of cost-to-benefit models. | |
| 8151587 | Incidence, prevalence and possible risk factors for pneumonitis in patients with rheumatoi | 1994 Jan | OBJECTIVE: Methotrexate (MTX) is being used increasingly to treat rheumatoid arthritis (RA). Pneumonitis is a serious side effect of MTX therapy (P-MTX). Our aim was to determine in patients with RA the incidence and prevalence of P-MTX in Western Australia and identify risk factors for the development of this adverse reaction. METHODS: Patients with P-MTX were identified by (a) direct communication with rheumatologists in Western Australia, (b) use of a computerized clinical database, (c) questionnaire inquiry of all other rheumatologists in Australia. Possible risk factors for P-MTX were examined using age/sex matched case controls selected from the computerized clinical database. RESULTS: Ten definite and 3 probable cases of P-MTX were identified. Local incidence of P-MTX was 1/35.4 patient years MTX treatment; if definite and probable cases are included (1/49.6 patient years MTX treatment for definite cases alone). Twelve patients with P-MTX were compared with 24 age/sex matched controls. A shorter duration of MTX treatment and a higher incidence of preexisting lung disease were observed in P-MTX cases but these differences were not statistically significant. No difference was observed between the P-MTX and control patients with respect to rheumatoid factor, duration of RA, use of tobacco, dose of MTX, serum creatinine, creatinine clearance or concurrent treatment with aspirin, nonsteroidal antirheumatic drugs or prednisolone. CONCLUSION: Our results indicate that in hospital clinic patients with RA pneumonitis is a common adverse reaction. They suggest that hypersensitivity is probably responsible for most cases of pneumonitis associated with MTX, but preexisting lung disease may confer increased risk. | |
| 1358078 | Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid ar | 1992 Oct | OBJECTIVE: Preferred drugs for rheumatoid arthritis (RA) should be those that have maximal efficacy with the least toxicity. We evaluated the efficacy and toxicity tradeoffs for drugs frequently used in the treatment of RA. METHODS: We updated 2 metaanalyses of published clinical trials, by adding trials published through 1990 and trials of azathioprine (AZA). We tested 3 different definitions of efficacy, each plotted against 3 different toxicity measures, for antimalarial drugs, methotrexate (MTX), auranofin, injectable gold, D-penicillamine, sulfasalazine (SSZ), AZA, and placebo. Efficacy measures included composite efficacy (a combination of joint count, grip strength, and erythrocyte sedimentation rate), tender joint count alone, and a measure based on how many patients dropped out due to inefficacy. Toxicity measures were the proportion dropping out due to toxicity, the same dropouts with side effects weighted for severity using a modification of a published toxicity index, and the proportion with severe toxicities (defined as a score of at least 7 of 10 on the toxicity index). The latter were usually organ toxicities (e.g., cytopenias and renal involvement). RESULTS: All 9 efficacy/toxicity tradeoff plots suggested that MTX and antimalarial drugs had the highest efficacy relative to toxicity. MTX scored among the most efficacious of the drugs and, of these, had the least toxicity. Antimalarial drugs, though showing only moderate efficacy, had the lowest toxicity rate of all the drugs. SSZ scored close to MTX but was, in general, slightly more toxic. CONCLUSION: In the short-term context of clinical trials, antimalarial drugs and MTX have the best efficacy/toxicity tradeoffs and may, therefore, be the preferred drugs. | |
| 7966061 | A Canadian survey of current methotrexate prescribing practices in rheumatoid arthritis. | 1994 Jul | OBJECTIVE: To conduct a cross sectional survey of methotrexate (MTX) prescribing practices of Canadian rheumatologists in their treatment of rheumatoid arthritis (RA). METHODS: A 15-item questionnaire was mailed to 197 rheumatologists with a 79% response rate after 3 mailings. RESULTS: The usual starting dose was 7.5 mg/week (range = 2.5-15.0) and the usual maximum dose prescribed was 15 mg/week (range = 10-50); 81% routinely coadministered MTX and non-steroidal antiinflammatory drugs; 28% routinely used folic acid prophylaxis; 97% of respondents performed regular assessments of liver function. Only 17% requested a liver biopsy after a certain time and 23% after a certain cumulative dose. Sixty-two percent performed pre-MTX liver biopsy on patients with liver function abnormalities. Only 14% of respondents routinely performed pulmonary function tests. Ninety-one percent of respondents noted that 1-50% (mode = 10%) of patients refused to accept MTX therapy after it had been recommended, usually because of fear of side effects. CONCLUSION: Despite potential toxicity, the majority of respondents used MTX in the treatment of adult RA. | |
| 7912633 | Methotrexate and sulphasalazine as combination therapy in rheumatoid arthritis. | 1994 Jul | Sulphasalazine (SASP) and methotrexate (MTX) are well-established treatments for RA but the use of these drugs in combination has been avoided as both have antifolate activity. In this paper we report our experience with 32 patients treated with the combination MTX/SASP and compare the toxicity and tolerability of the combination with 63 patients treated with MTX alone. The median duration of exposure to the combination was 23 months. Nineteen patients have continued this regime for over 18 months. Five patients on MTX/SASP combination discontinued MTX, in four cases due to toxicity and in one because MTX/SASP was ineffective. In 17 patients on MTX alone, the drug was withdrawn permanently. In seven cases the cause was toxicity including two patients with severe reactions. In patients known to tolerate SASP alone, the combination of MTX/SASP is also well tolerated. In our experience of 48 patient-years of such combination therapy, there is no increase in toxicity compared to therapy with MTX alone in RA. | |
| 8785891 | Methotrexate and other chemotherapeutic agents used to treat psoriasis. | 1995 Oct | The oral chemotherapy agent methotrexate remains a mainstay for the treatment of moderate to severe psoriasis after 40 years experience. Extensive usage, both for psoriasis and rheumatoid arthritis patients, has continued the reasonable safety profile for this drug when appropriate precautions are taken. The availability of other treatment modalities for severe psoriasis permits a rotational system with periods of time when methotrexate is not used, thereby lessening the risk of long-term side effects. Other chemotherapeutic agents for psoriasis are described, but they are used infrequently. | |
| 8348281 | Methotrexate--the relationship between dose and clinical effect. | 1993 Aug | Methotrexate (MTX) is an effective anti-rheumatic drug. Despite its frequent use, the relationship between different MTX doses and clinical effects remain unclear. In a randomized double-blind study in patients with RA, the effects of four MTX doses (5 to 20 mg) was studied. MTX (5 mg) induced a significant effect on the Ritchie joint index, morning stiffness, pain, ESR and C-reactive protein. The effect of MTX on those variables was related to the dose in the range from 5 to 20 mg MTX weekly. Interindividual differences in dose-response curves were observed. The study shows that MTX doses should be adjusted individually for each patient in order to improve efficacy and decrease dose-dependent side effects. | |
| 8668981 | [Methotrexate treatment of rheumatoid arthritis]. | 1996 Apr 27 | Weekly low dose methotrexate has a beneficial efficacy: toxicity ratio compared to other disease-modifying antirheumatic drugs. Methotrexate shows one of the most pronounced effects on disease activity, with improvement of functional status and slowing of radiological progression of joint destruction. In addition, the short- and medium-term withdrawal rate is low and due to usually minor side effects. However, major complications such as interstitial pneumonitis, hepatic fibrosis and osteopathy deserve special attention, in particular during long-term treatment. Careful patient selection and monitoring, in close cooperation between the rheumatologist and general practitioner, contribute to optimal security of methotrexate treatment. The present overview summarizes scientific data and makes practical recommendations. |