Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2487708 | Natural history and treatment decisions in rheumatoid arthritis revisited. | 1989 Sep | Compliance with RA therapeutic intervention must be viewed within the context of the natural history of the disease with or without drug treatment. Published studies from the 30s to the 80s provide a grim picture: both premature death and marked functional morbidity occur even in population-based analyses. Intervention with drugs appears to have short-term gains with little impact beyond 2 years. The reasons for this apparent paradox are two-fold. (1) our drugs are not as successful as we would like; and (2) clinical trials and long-term outcome studies exaggerate their differences from each other by selection criteria and other methodologic issues. Nevertheless, the picture that is emerging for the 90s is revolutionary. Patients with the worst prognosis are being treated more aggressively earlier in their course, and those that have a favorable prognosis do well without aggressive management and are treated differently. Traditional outcome measures are giving way to others that are more realistic and patient-oriented. The assumption that more (not less) treatment will remedy the situation is being tested. The impact of the success of Methotrexate on this change in philosophy should not be underestimated. | |
| 2028435 | Pneumocystis carinii pneumonia complicating low dose methotrexate treatment for rheumatoid | 1991 Mar | Low dose methotrexate has been used effectively for various rheumatic and non-rheumatic diseases. Three cases of Pneumocystis carinii pneumonia occurring during treatment of rheumatoid arthritis with low dose methotrexate are presented. Several mechanisms might contribute to impaired immunity and the rare development of opportunist lung infection with methotrexate. A high degree of suspicion may result in earlier diagnosis and treatment. | |
| 2663418 | New perspectives of secondary and tertiary therapy for rheumatoid arthritis. | 1989 May | Rheumatoid arthritis continues to be recognised as a disorder with a variable prognosis, but recent studies have emphasised its potential for shortening life span. Epidemiological, genetic, and natural history studies have helped to identify patients who are at risk for the development of more aggressive disease earlier in their clinical course, and rheumatologists are willing to be more aggressive in their treatment now as their armamentarium expands. Earlier separation of drugs into anti-inflammatory and immunomodulatory agents becomes irrelevant as these concepts change and drugs fulfil both definitions. Sequences of therapy continue to be dictated by the potential of toxicity and generally follow rather than precede disease progression. The addition of several new agents to the algorithms of therapy against rheumatoid arthritis raises questions about their effects and place in therapeutic regimens, especially as concerns auranofin, sulphasalazine, methotrexate and cyclosporin. Combination therapy is currently at the end of the drug line, but the therapeutic horizon beckons with the potential of biological agents aimed at the restoration of immune balance. | |
| 3330296 | Prospects in the immunological treatments of rheumatoid arthritis. | 1987 | Different trends in the therapeutic immunomodulation of rheumatoid arthritis (RA) have been developed since a few years. Early treatment and/or combined treatments using 2 or 3 classical remission inducing drugs could improve the clinical results. Diet and especially eicosapentanoic acid could influence the clinical signs of RA. Among the non specific immunodepressive agents, methotrexate is of major interest. Immunodepressive agents partly selective of a lymphocyte subpopulation: cyclosporin A, total lymphoid irradiation, act on CD4 cells. Some experimental immunomodulating drugs are under study: type II interferon, thymic hormones, immunoglobulins of placental origin. The specific immunotherapy of RA is still experimental and only used in animal with very promising results. Anticlass II HLA monoclonal or polyclonal antibodies could be one of the major treatments of autoimmune diseases within a few years. The treatment of RA by anti-idiotype antibodies remains, at this moment, theoretical. | |
| 3415364 | Methotrexate in rheumatoid arthritis: a prospective study in Israeli patients with immunog | 1988 Aug | In a prospective open study 44 Israeli patients with rheumatoid arthritis were treated with weekly low dose methotrexate (MTX) for up to 36 months. Nine patients withdrew from the study: six because of side effects and three due to inefficacy. One patient died of septicaemia following septic arthritis. Significant improvement, graded by Ritchie articular index, grip strength, physician's global assessment, erythrocyte sedimentation rate (ESR), and platelet counts, was noticed in response to treatment. Seronegative patients had a better clinical response. Transient gastrointestinal symptoms were common and correlated with increases of serum aspartate transaminase (AST). HLA-DR1 and DR7 were significantly associated with increased serum AST concentrations. | |
| 2205907 | Clinical and laboratory outcomes during the treatment of rheumatoid arthritis with methotr | 1990 | Ten clinical and three laboratory outcomes were evaluated in 86 patients completing a double-blind placebo-controlled trial of methotrexate in rheumatoid arthritis. The improvement in all measured outcomes was statistically significantly better in patients receiving methotrexate than in patients receiving placebo. The correlations of the changes in outcome measures were calculated to determine if improvement in one parameter was associated with improvement in other clinical parameters. Associations between different clinical outcomes were often statistically significant. Associations between laboratory outcomes were also often statistically significant. However, the association between clinical outcomes and laboratory outcomes was generally poor. | |
| 1971456 | [Does the general strategy for the treatment of rheumatoid polyarthritis need to be review | 1990 Apr 10 | At the start of the nineties, the therapeutic strategy for rheumatoid arthritis (RA) is still disappointing, and the natural history of this affection remains only slightly influenced by the treatments; a general re-assessment of the treatment seems therefore justified. Some new slow acting drugs are effective, but they cannot be considered as being therapeutic revolutions: gold salts per os, sulphasalazine, tiopronine whose efficacy is comparable to D-penicillamine without systematic cross interaction, methotrexate, cyclosporin which is difficult to manipulate. These observations encourage the search for new strategies, namely for the early treatment of the synovitis before the pannus and radiological signs appear. For this, the early and irrefutable diagnosis of RA must be made possible; and no completely reliable, early detection test is available yet. Though promising, the new therapeutic approaches, immunomanipulation or cell manipulation, do not revolutionize the evolution of this pathology. Other fields of research need to be developed, namely on the remission-inducing agents observed during pregnancy. It is still impossible to know which approach will provide the absolute weapon against RA. | |
| 1877853 | Two methods of assessment of methotrexate hepatotoxicity in patients with rheumatoid arthr | 1991 Jul | Serial liver biopsy specimens from 18 patients with rheumatoid arthritis receiving a weekly dose of methotrexate 7.5-20 mg for a minimum of 12 months were assessed semiquantitatively and by a microcomputer image analysis system. The semiquantitative histological method showed a significant increase in pericellular collagen and in overall disease while morphometry showed a significant increase in pericellular, perivenular, and portal tract collagen. There was a significant correlation between the two methods, but morphometry had the advantage of objectivity and efficiency. There was no correlation between the increase in collagen and the accumulated dose of methotrexate, which suggests that other factors in addition to methotrexate may contribute to liver injury. | |
| 2504917 | Short term effects of low dose methotrexate on the acute phase reaction in patients with r | 1989 Jul | Sequential daily measurements of erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) were performed for one week after an I.V. injection of 7.5-13 mg methotrexate (MTX) in 18 patients with rheumatoid arthritis. Early decreases of ESR and CRP were observed. Serum CRP was more sensitive than ESR, displaying more pronounced falls from baseline to both the minimal and to the 7th day levels. Patients receiving their first dose of MTX (n = 9) exhibited a more prominent reduction of CRP levels in comparison to veteran MTX users (n = 9). The prompt response of acute phase reactants to MTX may correspond to the relatively rapid clinical effect of the drug in RA. It may also support an antiinflammatory mechanism of action of low dose MTX. | |
| 1929588 | Nocardia asteroides pneumonia complicating low dose methotrexate treatment of refractory r | 1991 Sep | Low dose methotrexate is used increasingly often in the treatment of rheumatoid arthritis. Severe complications due to toxicity of the lung or bone marrow occur infrequently. This report describes a 71 year old woman with longstanding rheumatoid arthritis who developed pleuritis, a pulmonary infiltrate, and pancytopenia during treatment with low dose methotrexate. Fatal respiratory insufficiency followed, and cultures from the lung after death showed Nocardia asteroides. | |
| 3422013 | In vitro rheumatoid factor synthesis in patients taking second-line drugs for rheumatoid a | 1988 Sep | Rheumatoid arthritis (RA) patients whose unstimulated peripheral blood mononuclear cells produce high levels of IgM rheumatoid factor (IgM-RF) in vitro have more severe disease activity. RA patients being treated with second-line agents, including gold salts, penicillamine, or methotrexate, tend to be low producers or nonproducers of IgM-RF in vitro. The possibility that low production or nonproduction of IgM-RF in vitro may be explained by treatment with second-line agents alone, irrespective of disease activity, was analyzed in 133 RA patients whose disease status was assessed by multiple laboratory and clinical measures. The results indicate that treatment with second-line agents and in vitro IgM-RF synthesis are independently associated with disease activity. | |
| 1712419 | [High-dose immunoglobulins for the treatment of rheumatoid arthritis: pilot study of 7 cas | 1990 Oct | High intravenous doses (400 mg/kg) of gammaglobulin (IVIG) were administered monthly for six months to 7 patients with severe rheumatoid arthritis (RA). In all cases, previous treatment with NSAIDs and corticosteroids and in 3 of them with gold and/or methotrexate had been ineffective. A 50 per cent improvement of Ritchie index was obtained in 6/7 patients, morning stiffness was reduced from greater than 2 hours to less than 30 minutes in 6/7 patients. Swollen joints and Lee index improved in all patients. ESR did not show any change but RCP improved in 6/7 patients. The study of lymphocyte subpopulation showed no substantial changes in CD20+, CD3+, CD4 and CD8 cells as well as in CD4/CD8 ratio and a significant increase in 2H4+T cells without changes in 4B4+ subpopulation. IVIG improved the clinical and laboratory features of patients with severe RA. The major problem raised by IVIG therapy is its high cost suggesting that this therapy should only be applied in well selected patients with RA. | |
| 2799303 | Methotrexate treatment of rheumatoid arthritis: effects on radiological progression. | 1989 | Radiological progression was evaluated in 15 patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Prior to MTX treatment, all the patients had failed on other slow-acting agents and all showed radiological deterioration. For each patient, three sets of radiographs of hands and wrists were evaluated: prior to MTX treatment while on other slow-acting agents, at the beginning of MTX treatment, and at the most recent evaluation on MTX. Two experienced radiologists evaluated the radiographs independently. The rate of radiological progression was calculated by dividing the change in radiological score by the number of months between sets of radiographs. The mean time from film set one to two (period one) was 29.4 months and from set two to three (period two) 32.5 months. The mean rate of radiological progression for period one was 0.576 and for period two, 0.381. Eight patients showed decline in radiological progression during MTX treatment. | |
| 2084237 | Radiologic progression during intramuscular methotrexate treatment of rheumatoid arthritis | 1990 Dec | The radiographic evolution of joint lesions in 41 patients with severe and longstanding rheumatoid arthritis (RA) (mean duration: 12.9 years) treated with methotrexate (MTX) for more than 24 months (mean 31.2 months) was studied in a double blind manner by 2 rheumatologists using Larsen's score. All the patients were clinically improved. The radiological study of hands and wrists was possible in only 37 of 41 patients for surgical reasons. We found a deterioration of joint lesions in 31 cases (83.8%), a stabilization in 6 cases (16.2%). MTX does not appear to be able to slow down the radiographic evolution of RA. Whether it could prevent the radiologic progression in early RA remains to be elucidated. | |
| 2281394 | [Megaloblastic pancytopenia in a female patient with rheumatoid arthritis given methotrexa | 1990 | The paper is concerned with the development of megaloblastic pancytopenia in a female patient with grave rheumatoid arthritis. The patient had been given methotrexate (15 mg per week) for a long time, supplemented by amidopyrine (1.0 to 1.5 g/day). The author holds that the development of the above-indicated complication is provoked by both drugs interference into folate metabolism. It is concluded that caution should be taken as to the combined use of methotrexate with non-narcotic analgesic drugs, nonsteroidal anti-inflammatory agents and sulfanilamides. | |
| 2123248 | Medical treatment for rheumatic diseases. | 1990 Oct | Rest, physiotherapy, joint protection, patient education and counselling all play an important role alongside drug therapy and surgery in the management of a chronic disorder such as rheumatoid arthritis. Patients expect their physician to take the initiative in integrating the members of the multi-disciplinary team devoted to their care. The physician will also instigate drug therapy. In early disease, an analgesic ('for pain') may supplement a non-steroidal anti-inflammatory drug ('for stiffness'). A variety of such drugs are available with various advantages and disadvantages. For more severe, progressive disease a 'second-line' or disease-modifying drug may be prescribed. Typical examples are injectable gold, penicillamine, antimalarials, sulphasalazine and methotrexate. The prescription of any of these represents a calculated risk: the benefits of treatment have to be balanced against the likely side-effects. A variety of intra-articular treatments are also available for providing some localisation of response and sometimes obviating the need for surgery which should be the subject of close collaboration between the rheumatologists and orthopaedic surgeons. | |
| 2473207 | Liver biopsy findings in patients with rheumatoid arthritis undergoing longterm treatment | 1989 Apr | Ten histological criteria were evaluated semiquantitatively in the liver biopsies of 60 patients with rheumatoid arthritis (RA) before initiation of methotrexate (MTX) and were compared with 40 biopsies taken during MTX treatment (mean cumulative dose 1.322 mg). Mesenchymal changes (Kupffer cell proliferation, portal tract infiltration) and parenchymal alterations (nuclear variability, ballooning, fatty infiltration) were very common without statistically significant difference between the 2 groups. Slight periportal and/or portal fibrosis was present in 25% of patients without statistical difference between groups. Central fibrosis occurred in 13.5-12.5%. We conclude that liver abnormalities in RA are not related to MTX treatment. | |
| 2261733 | Can treatment with methotrexate influence the radiological progression of rheumatoid arthr | 1990 Sep | We have recently reported that methotrexate (MTX) is an effective treatment of patients with refractory rheumatoid arthritis (RA) to second line medication. We showed that 54% of our patients continued having clinical benefit after 24 months therapy with MTX. In this study we evaluated pairs of hand radiographs from 35 patients taken before and after 24 months treatment. We used a scale scoring similar to Larsen's standard radiographs with minor modifications. No significant changes were observed in the overall scoring of the radiographs before (14.84 +/- 13.05) and after treatment (18.77 +/- 15.60) (p greater than 0.5). Of these 35 patients, 23 had a clinical remission and 12 had a good response. Twenty patients have shown a stabilization of erosions in radiographs while 15 showed a deterioration. No correlation was found between clinical response and radiological changes. We conclude that MTX does not appear to be a disease modifying agent, but may inhibit joint damage progression. | |
| 2706419 | Prospective long term follow-up of methotrexate therapy in rheumatoid arthritis: toxicity, | 1989 Apr | We followed all 128 patients started on methotrexate (MTX) for rheumatoid arthritis (RA) over a 4-year period. Forty-nine were followed for over 3 years. Forty-three patients discontinued treatment, 23 because of toxicity, 15 for inefficacy and five for other reasons. Forty-seven of the 75 followed on treatment for over 2 years had hand radiographs available before and after this treatment period. None showed improvement and 15 showed marked deterioration. Patients' acceptance of this therapy was good although most were noted objectively to have persistent disease activity. We would recommend that if MTX is to be used, a more aggressive approach be adopted to reduce not only the symptoms but the signs of active disease. | |
| 1865411 | Analysis of methotrexate treatment effect in a longitudinal observational study: utility o | 1991 May | We studied 235 patients with rheumatoid arthritis (RA) beginning therapy with methotrexate utilizing a k-means clustering algorithm. Four groups were identified: mild RA (Group 3), very severe RA (Group 4), and 2 groups intermediate in severity (Groups 1 and 2). Group 2, the largest of the clusters (n = 89), appeared to have greater tolerability of RA as measured by severity and psychological variables, and took the drug almost twice as long as other groups, although improvement was not greater nor side effects fewer. All groups improved over a mean of 1.9 years, and the degree of improvement was not related to the initial severity classification. Improvement occurred almost equally in all clusters, and the relative ranking of the groups was maintained at study closure. |