Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2047554 | [Rheumatoid arthritis and chronic granular T-cell lymphocytosis with neutropenia. A clinic | 1991 Mar | 103 cases of rheumatoid arthritis who had been diagnosed between 1984 and 1985 have retrospectively been analyzed, in order to identify those patients who had presented with associated neutropenia and in whom it was thus possible to suggest a presumptive diagnosis of either Felty's syndrome or chronic granulated lymphocytosis with neutropenia. Four patients (3.8%) satisfied the clinical criteria for the latter diagnosis while only one had typical Felty's syndrome. They were again studied using blood counts, microscopy of bone marrow and surface antigen analysis of mononuclear cells and the above mentioned diagnoses were confirmed. Though clinically indistinguishable, these two conditions are clearly distinct on both hematologic and immunological grounds. The four patients with rheumatoid arthritis and chronic granulated T cell lymphocytosis with neutropenia represent 36.3 per cent of our institution's patients with chronic granulated T cell lymphocytosis of undetermined significance. Caution should be used in the treatment of rheumatoid arthritis of the patients with associated granular lymphocyte proliferation, considering the possible adverse effects that drugs such as gold salts, penicillamine, cyclosporine and methotrexate may exert not only on the immunological system but also on granulocytopoiesis. | |
| 1972665 | Response of immunoregulatory lymphocyte subsets to methotrexate in rheumatoid arthritis. | 1990 May | In an attempt to define the immunoregulatory mechanisms operating in rheumatoid arthritis, the authors examined peripheral blood functional lymphocyte subsets in 15 patients with active rheumatoid arthritis who were not receiving remittive therapy, as well as 33 healthy controls. The percentage and absolute numbers of total T cells (CD3), T-helper/inducer cells (CD4), and T-suppressor/cytotoxic cells (CD8) did not differ among the groups, nor did the CD4:CD8 ratio or the numbers of T cells coexpressing CD4 and the activation markers Ia or IL-2R. However, rheumatoid arthritis patients did have reduced percentages and numbers of CD4+ cells coexpressing the 2H4 antigen (CD45R-naive T cells) (P less than .0003) and CD8+ cells coexpressing the Leu-15 (CD11b) marker (suppressor/effectors) (P less than .0005). Twelve patients then received oral methotrexate, 7.5 mg weekly. Most showed clinical improvement by 4 weeks and all did by 8 weeks. Although changes in the T-cell subsets were not statistically significant, several tended toward normalization. These findings may help explain the immunoregulatory defect in rheumatoid arthritis and the effectiveness of methotrexate in modifying disease activity. | |
| 2009648 | Disease-modifying agents and experimental treatments of rheumatoid arthritis. | 1991 Apr | The pharmacologic management of the rheumatoid arthritis (RA) patient involves the use of various classes of therapeutic agents to induce symptomatic relief and reduce disease activity. Aspirin and nonsteroidal antiinflammatory drugs are used initially to lessen the degree of pain and swelling associated with the inflammatory disease process. The addition of a heterogeneous class of compounds, "second-line" therapy (previously known as disease-modifying antiinflammatory rheumatic drugs), is advocated to modify the disease course itself. Second-line treatments include antimalarials, gold salts, D-penicillamine, azathioprine, and methotrexate. Randomized placebo-controlled trials ahve demonstrated the efficacy of these compounds in RA. Improvement in standard parameters of disease activity including the number of painful and swollen joints, duration of morning stiffness, and erythrocyte sedimentation rate has been noted with these second-line drugs. Whether they modify roentgenographic progression is under rigorous study. These agents alone or in combination rarely induce complete disease remission. Therefore, newer therapies are under intensive investigation and include sulfasalazine, cyclosporin A, and combination therapy. | |
| 3288222 | A long-term prospective study of the use of methotrexate in rheumatoid arthritis. Update a | 1988 May | Twenty-five patients have completed a mean of 53 months of treatment with methotrexate (MTX) as part of a prospective study of the long-term safety and efficacy of the drug. Since the time of the last report (at a mean of 29 months), the mean dosage of MTX has increased from 12.4 mg/week to 14.6 mg/week, whereas the mean prednisone dosage has decreased from a baseline of 7.1 mg/day to 1.9 mg/day. A significant improvement from baseline in all clinical parameters tested was maintained, and response to therapy did not vary significantly between the assessment at 29 months and that at 53 months. Toxic reactions were as common during months 30-53 as during the first 29 months of the study, with patterns of toxic reactions remaining consistent within each patient. Radiologic evidence of disease progression was not seen before 24 months of MTX treatment, but after this time, it was observed in some patients. We conclude that many clinical features of long-term MTX therapy are distinctly different from what might have been expected after the short-term trials. | |
| 1744528 | The use of long-acting drugs in the treatment of rheumatoid arthritis. | 1991 Sep | Experience to date strongly indicates that long-acting drugs currently used in treatment of rheumatoid arthritis are very potent antiinflammatory agents which act in most cases by completely unknown mechanisms. All of them have built in but recognizable toxicity which can usually be prevented by appropriate monitoring. Although most of them offer relatively short term (up to 3 years) benefits, with the probable exception of methotrexate, nonetheless they can offer for a period of time improved function and relief of pain for many individuals. Thus, even though they do not dramatically affect the long-range outcome of the disease, they continue to offer useful benefit for patients with rheumatoid arthritis who are not responding to conservative therapy. Some of the long-acting agents are only slightly more toxic than the widely nonsteroidal antiinflammatory drugs which do have a definite risk of serious upper gastrointestinal bleeding. Currently the use of combinations as well as the continued introduction of new drugs in this class, offer hope that greater benefit than we can currently provide is within reach over the next few years. | |
| 2672136 | Methotrexate therapy in the treatment of rheumatoid arthritis. | 1989 Aug | MTX has been demonstrated to be one of the most effective agents in current use for the treatment of patients with active RA who have failed other approaches. Therapy must be individualized to achieve an optimal efficacy/toxicity profile. The drug is a potent steroid-sparing agent which is a factor of marked significance in this patient group. Although cellular activity is well described, many unanswered questions about its absorption, target cell population, and mechanism of action remain. More information is needed about the true incidence of long-term toxicities to be able to better address the all important issue of when to use MTX in the treatment of RA. Research efforts, including studies of immunologic parameters over time, are needed to achieve a better understanding of the drug's mechanism of action. Lastly, the reasons for the plateau in clinical response to MTX should be explored to devise strategies to enhance and sustain the effects of this already potent drug. | |
| 2029152 | Drug treatment of progressive rheumatoid arthritis. | 1991 Jan | The drug treatment of progressive rheumatoid arthritis (RA) is discussed with emphasis on second line agents used both singly and in combination. NSAIDS play a supportive role in the management of RA. Low dose prednisolone is acceptably safe and effective in long term use whereas pulsed steroids and intra-articular use is reserved for short term control of disease. Antimalarials are rarely valuable as sole agents in progressive arthritis. The use of sulphasalazine, gold thiomalate, d-penicillamine, auranofin, methotrexate, azathioprine and cyclophosphamide in rheumatoid arthritis and their place in the therapeutic strategy are discussed. The reported use of combination chemotherapy has not shown the expected additive benefits although azathioprine, methotrexate and hydroxychloroquine combination may prove to be better than single agents. Recently cyclosporine and gamma interferon have not been shown to be highly efficacious. Of the new therapies monoclonal antibodies to CD4 and CD5 positive lymphocytes are showing promise of marked efficacy in the short term. Sustained control of synovitis appears to improve the long term outcome but better strategies and better drugs are needed. | |
| 2084236 | Adverse experience with methotrexate during 176 weeks of a longterm prospective trial in p | 1990 Dec | Adverse experience occurred with a high frequency in a longterm (greater than 3 years), prospective, double blind, followed by an open trial of methotrexate (MTX) therapy in 45 patients with rheumatoid arthritis (RA). Adverse experiences occurred in 96% of patients, and the discontinuation rate was 44% over 176 weeks. No hepatic or pulmonary fibrosis occurred. Unusual toxicities included weight loss (2 patients), systemic fungal infections (2 patients), and transient noncirrhotic ascites (1 patient). Baseline white blood cell counts and creatinine may help predict adverse experiences. The full dose-toxicity spectrum of MTX RA is not yet fully defined. | |
| 2396863 | Liver histology in patients receiving low dose pulse methotrexate for the treatment of rhe | 1990 Aug | The liver histology of 52 patients treated with intermittent low dose pulse methotrexate for rheumatoid arthritis was evaluated using a modification of the Roenigk grading system. Patients studied had had an average of 3.2 years of treatment or had received 1.7 g methotrexate. No patient had cirrhosis; 15 (29%) patients had evidence of mild fibrosis. Histological abnormalities were not predicted by liver function test changes, with the exception that hypoalbuminaemia occurred in 60% of those with grade IV (modified criteria) findings. The need for liver biopsy in patients with rheumatoid arthritis treated with methotrexate before two years or 1500 mg of treatment has not been established. Whether serial liver biopsies will be needed beyond this time has yet to be determined. | |
| 2622275 | [Sicca syndrome caused by large granulated lymphocytes in rheumatoid arthritis]. | 1989 Dec 9 | The proliferation of large granulated T lymphocytes (LGL) with neutropenia and splenomegaly can be observed in patients with rheumatoid arthritis (RA), in a similar way to Felty's syndrome. We report a female with long standing AR, xerophthalmia, xerostomia, neutropenia and LGL lymphocytosis. The phenotype of the latter was CD3+, CD8+, HNK1+. She was treated with methotrexate and corticosteroids. The genetic rearrangement study did not show monoclonality. Although LGL lymphocytosis can infiltrate several organs, salivary glands infiltration has not been reported. The development of a sicca syndrome can be a feature of LGL lymphocytosis and induce diagnostic mistakes in RA. | |
| 3054093 | In vivo effects of antirheumatic drugs on neutral collagenolytic proteases in human rheuma | 1988 Aug | The destruction of joints in rheumatoid arthritis (RA) is thought to be related in part to an increased synthesis of proteolytic enzymes. We have determined neutral collagenolytic protease activity levels in human RA synovia and articular cartilage and examined the in vivo effects of various therapeutic regimens on enzyme levels. Neutral metallocollagenolytic enzyme (NMCE) was measured in 29 RA cartilages and synovial membranes. In addition, synovial serine protease levels were determined. Specimens were divided into 4 groups according to prescribed medications: (1) nonsteroidal antiinflammatory drugs alone; (2) steroids alone; (3) steroids and gold; and (4) steroids and methotrexate (MTX). Ten normal specimens were used as controls. Total and active NMCE measured in both RA cartilage and synovial membrane specimens showed a significantly higher level of activity than in controls (p less than 0.0001, p less than 0.005; p less than 0.004, p less than 0.02). MTX was found to markedly decrease NMCE activity; cartilage NMCE level in patients with RA receiving MTX was reduced, compared to the other subgroups. This was particularly noted for the active form. Synovial NMCE levels from the MTX subgroup for both enzyme forms were much lower than in any other RA subgroup, significantly lower than in the RA group as a whole (p less than 0.05), and similar to controls. RA synovial membrane serine protease activity showed an increase compared to controls. Again, MTX markedly decreased the activity of this class of enzyme. Our data strongly support the role of neutral proteases in the destruction of RA joints. MTX was the only drug to consistently decrease these enzyme levels in joint tissues. | |
| 1856803 | Methotrexate in rheumatoid arthritis: effects on disease activity in a multicenter prospec | 1991 Mar | One hundred and twenty-three patients with rheumatoid arthritis (RA) who successfully completed a randomized trial comparing oral methotrexate (MTX) to auranofin enrolled in a longterm prospective study of oral MTX. Of the 91 patients who completed 24 months of therapy, a significant (p = 0.0001) improvement was noted compared to baseline in all clinical disease variables and the Westergren erythrocyte sedimentation rate (ESR). Marked improvement occurred in 94 (76%) and 98 (80%) of the patients in the joint pain/tenderness index and joint swelling index at the last evaluable visit (mean 26 months). Of the 77 patients with an elevated ESR at baseline, 29 (38%) patients normalized it (less than 20 mm/h) while receiving therapy (p less than 0.01). A significant reduction in prednisone dose was also seen. Adverse events occurred frequently but were generally mild in severity. Twenty-seven patients (22%) withdrew during the study. Four (3%) withdrew due to lack of efficacy, and 6 (5%) because of adverse experiences. The overall probability of continuing therapy in the study for 48 months was projected at 72%. This large prospective study supports the observation of earlier smaller studies that MTX is an effective drug in the treatment of RA. | |
| 1768158 | Exacerbation of rheumatoid arthritis in patients treated with methotrexate after administr | 1991 Dec | A double blind, placebo controlled trial examined the effects of folinic acid on the efficacy and toxicity of methotrexate in 27 patients with rheumatoid arthritis. Clinical and laboratory indices of disease activity worsened significantly in the 13 patients treated with folinic acid after four weeks of treatment, but not in the 14 patients treated with placebo. Exacerbation of rheumatoid arthritis led to withdrawal of the test drug in seven of the patients treated with folinic acid but in none of those treated with placebo. It is concluded that excerbation of rheumatoid arthritis is likely when folinic acid is given shortly after the weekly dose of methotrexate. | |
| 1941836 | Pneumocystis carinii pneumonia associated with methotrexate therapy in rheumatoid arthriti | 1991 Aug | Opportunistic infections occur in patients with rheumatic diseases treated with low dose methotrexate (MTX) with or without other immunosuppressants. Our case report illustrates a fatal case of Pneumocystis carinii pneumonia in a patient with rheumatoid arthritis treated with low dose MTX and glucocorticoid. A review of the literature reveals other opportunistic infections such as Cryptococcus, Nocardia, and herpes zoster presenting in such patients. These occurrences suggest that MTX should be used cautiously in patients with rheumatic disease receiving concomitant medical therapy. | |
| 2182169 | Comparative controlled trial of low-dose weekly methotrexate versus azathioprine in rheuma | 1990 Apr | Fifty-three patients with rheumatoid arthritis who required immunosuppressive therapy were commenced in a randomized trial comparing azathioprine to weekly oral pulse methotrexate. After an initial 24-week period, both groups had significantly improved from baseline measures of pain and functional capacity and there were no significant differences in clinical outcomes between the two groups. Laboratory variables of disease activity showed a significant improvement in haemoglobin and ESR in the methotrexate group. Subsequently, the patients were followed for up to 3 years. After one year, more than half of the patients in both groups had discontinued therapy due to inefficacy or adverse events. Adverse effects were more frequent in the patients treated with methotrexate, but withdrawal rates were similar in both groups. From these data, the probability of a patient continuing therapy with either agent for greater than 18 months is low. | |
| 3593431 | Immunologic studies of rheumatoid arthritis patients treated with methotrexate. | 1987 May | Immunologic functions of peripheral blood mononuclear cells were studied in rheumatoid arthritis (RA) patients treated with methotrexate (MTX). Spontaneous IgM rheumatoid factor (IgM-RF) synthesis by unstimulated cultured blood mononuclear cells was seen in only 3 of 18 MTX-treated patients, compared with 31 of 54 RA patients who were not receiving long-acting drugs. Total IgM production by unstimulated cultured mononuclear cells, pokeweed mitogen-induced antibody synthesis, and plasma levels of IgM-RF were also lower in MTX-treated patients than in other RA patients. The numbers of circulating B cells, T4 and T8 cells, the T4:T8 cell ratio, and mitogen-induced proliferation indices were similar in MTX-treated and non-MTX-treated patients. Eleven additional patients were studied prospectively after initiation of MTX therapy. All showed significant decreases in spontaneous IgM-RF synthesis, with declining IgM-RF:IgM ratios, including all of the 9 who were studied during the first 24 hours of treatment. The results indicate that MTX has rapid effects on IgM-RF synthesis, and this action might be associated with its therapeutic efficacy in RA. | |
| 3124860 | Folate status of rheumatoid arthritis patients receiving long-term, low-dose methotrexate | 1987 Dec | The folate status of 29 healthy control subjects, 16 rheumatoid arthritis (RA) patients taking methotrexate (MTX), and 20 RA patients who were not being treated with MTX was estimated by an assay of the folate-dependent enzymatic synthesis of serine from formate and glycine, which is termed the C1 index. Analysis of variance demonstrated that the specific activity of the enzyme system in lymphocytes was significantly lower in the MTX-treated group, with an activity approximately one-half that of the control and the non-MTX-treated groups. Since the C1 index is one of the first biochemical parameters found to be different between MTX-treated and non-MTX-treated groups, alterations in folate-mediated amino acid metabolism may be involved in the mechanism of response to MTX therapy. Use of the C1 index may assist in the development of protocols which preserve the efficacy of MTX therapy while minimizing toxicity. | |
| 1920331 | The effect of age on methotrexate efficacy and toxicity. | 1991 Jul | We studied the clinical course of 235 patients with rheumatoid arthritis (RA) receiving methotrexate (MTX) over a mean of 1.9 years. Both older (greater than 65 years) and younger (less than or equal to 65 years) patients demonstrated clinical improvement, but older patients had greater improvement in erythrocyte sedimentation rate and hemoglobin than younger patients. Most assessments of laboratory abnormalities and symptoms suggestive of toxicity did not differ between age groups. But more gastrointestinal complaints and pulmonary complaints were reported in older patients, associations that have been noted in older patients not treated with MTX as well. Our data indicate that treatment that includes MTX is effective in older patients with RA, and that older patients improve at least as much as younger. | |
| 2204217 | [Long-term drug treatment of chronic polyarthritis: current status and perspectives]. | 1990 Jun 30 | The therapeutic repertoire for the treatment of rheumatoid arthritis has been expanded to new disease-modifying antirheumatic drugs (DMARDs), like Auranofine, Sulfasalazine, and Methotrexate. Rheumatoid arthritis is not only a highly disabling disease but is now recognized to be related with increased mortality. Therefore, the aim of therapeutic strategies is the early induction of remission. The strategy for treatment of rheumatoid arthritis should be based on an analysis of the individual risk of a patient to develop severe illness. A concept of "risk-oriented DMARD-therapy" of rheumatoid arthritis is proposed. | |
| 2730263 | Methotrexate-associated, early-onset pancytopenia in rheumatoid arthritis. | 1989 Jun | A patient with rheumatoid arthritis presented with pancytopenia 3 weeks after initiation of low-dose methotrexate administered orally. She had minimal renal insufficiency and hypoalbuminemia prior to initiation of methotrexate therapy, and had received a nonsteroidal anti-inflammatory drug concurrently. Bone marrow recovery occurred within 3 weeks. Patients receiving low-dose methotrexate therapy for rheumatoid arthritis require early monitoring for bone marrow injury, especially those who have risk factors for possible methotrexate toxicity. |