Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2369419 | Hepatitis with bridging fibrosis and reversible hepatic insufficiency in a woman with rheu | 1990 Jul | A patient with seropositive rheumatoid arthritis developed ascites while taking weekly doses of methotrexate (MTX). Her serum transaminase and albumin levels were normal. A liver biopsy revealed chronic hepatitis with bridging fibrosis and piecemeal necrosis. Upon discontinuation of MTX, her ascites resolved, and her arthritis became more active. This is the third report of reversible hepatic decompensation associated with prolonged MTX therapy in patients with rheumatoid arthritis. | |
| 1920305 | Are the results of controlled clinical trials and observational studies of second line the | 1991 Jul | We studied 122 controlled clinical trials and observational studies of second line therapy that involved 16,071 patients. The mean disease duration was 7.61 years at study entry. Controlled clinical trials were inherently short term, and 90.5% of patients were followed for 1 year or less (mean 8.8 months). The mean followup of observational studies was 31 months. Outcome assessments that included functional measurements were rare in either study type, as were considerations of socioeconomic factors. Except for methotrexate, which was used longer, half of the studies indicated discontinuation of therapy after 1.5 years. Good retention rates in studies of 3 to 12 months were not representative of longterm results, but controlled clinical trials and observational studies were similar as to retention during the first treatment year. Observational studies following controlled clinical trials can yield important information about RA treatment effectiveness not available from controlled clinical trials alone. | |
| 2427090 | Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Asso | 1986 Jul | Serum and red blood cell methotrexate (MTX) levels, as well as hepatic levels of MTX and folate, were analyzed in 24 patients who had received long-term oral MTX weekly for the treatment of rheumatoid arthritis. The serum MTX level peaked rapidly and was insignificant after 24 hours. The red blood cell MTX level was not related to the interval from the last MTX dose. In hepatic tissue obtained by liver biopsy, MTX was found in a predominantly polyglutamated form with depleted hepatic folate stores when compared with baseline specimens. A brief period of therapy with oral folinic acid repleted hepatic folate. It is possible that MTX hepatotoxicity is related to reduced hepatic folate levels and formation of MTX polyglutamates. | |
| 3050087 | Concurrent use of folinic acid and methotrexate in rheumatoid arthritis. | 1988 Jul | In a double blind placebo controlled crossover study, each arm of 4 weeks' duration, 20 mg of folinic acid/week or placebo were administered to 13 patients with rheumatoid arthritis. These individuals were receiving weekly intramuscular methotrexate (MTX) but were about to discontinue because of side effects. While there was considerable improvement in nausea during the study, the effect of folinic acid could not be differentiated from that of placebo. There was no adverse effect on control of disease activity. It therefore seems likely that polyglutamated tissue stores of MTX do not contribute to drug efficacy and in this format folinic acid could not be shown to be more useful than placebo in reducing drug induced nausea. | |
| 1793024 | IgM-rheumatoid factor and responses to second-line drugs in rheumatoid arthritis. | 1991 Sep | We have examined the relationship between IgM-rheumatoid factor (RF) and responses to second-line drugs in patients with rheumatoid arthritis (RA). Patients with active RA who were beginning treatment with gold, methotrexate or both were studied. Clinical responses were assessed with ESR, joint count, grip strength and activities of daily living questionnaire scores. Production of IgM-RF by peripheral blood mononuclear cells in vitro and plasma levels of IgM-RF were measured by ELISA. Overall, 31 of 44 patients completing more than 6 months treatment improved including 10 treated with gold, 12 with MTX and 9 with both. Production of IgM-RF by peripheral blood mononuclear cells was decreased by 59% in patients who improved on treatment, but increased 2-fold in the unimproved group. Plasma levels of IgM-RF were decreased from 121 to 66 micrograms/ml in the improved group after 6 months of treatment, with similar decreases seen for each of the three treatments. In contrast, plasma IgM-RF levels in the unimproved group did not decrease until 1 year of treatment was completed. Nine patients converted to seronegativity, and all but one of these were in the improved group. The results suggest that IgM-RF is correlated with responses to second-line drug in RA patients. | |
| 3512929 | Therapeutic approaches to the treatment of rheumatoid disease. | 1986 Mar | Successful treatment of patients with rheumatoid arthritis demands an understanding of the rationale, clinical use, and side effects of the various antirheumatic modalities. Most patients can be treated effectively with salicylates or other nonsteroidal anti-inflammatory drugs, although some with more serious disease require the addition of a slow-acting agent such as gold, d-penicillamine, or methotrexate. | |
| 2003511 | Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotre | 1991 Mar | PURPOSE: Herpes zoster occurred in nine patients with methotrexate-treated rheumatoid arthritis. We compared these patients to a large group of methotrexate-treated rheumatoid arthritis patients in order to uncover potential factors explaining the occurrence of herpes zoster. PATIENTS AND METHODS: Data from 187 patients taking methotrexate were reviewed and compared with data from another nine patients who developed herpes zoster while taking the drug for rheumatoid arthritis, all from the same university-based arthritis clinic. Literature pertinent to infection in rheumatoid arthritis patients treated with methotrexate is reviewed. RESULTS: Herpes zoster occurred in 14.5 cases per 1,000 patient-years in our methotrexate-treated rheumatoid arthritis patients, as compared with the general population incidence of 1.3 to 4.8 cases per 1,000 patient-years. The infection was unrelated to duration of methotrexate usage, prednisone treatment, or the co-existence of diabetes mellitus, but appeared to occur in patients with high titers of rheumatoid factor and an overall longer duration of rheumatoid arthritis. There were no cases of systemic dissemination or recurrence of herpes zoster despite 27.4 years cumulative follow-up on continued methotrexate therapy. CONCLUSIONS: Herpes zoster may occur more frequently in patients with rheumatoid arthritis treated with low-dose methotrexate than in the general population. Herpes zoster in rheumatoid arthritis patients treated with methotrexate appears to be self-limited, benign, and statistically related to methotrexate use in the presence of longer-term rheumatoid disease. | |
| 2001072 | Increased TNF-alpha secretion by alveolar macrophages from patients with rheumatoid arthri | 1991 Mar | Tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) production by alveolar macrophages (AM) was evaluated in 17 rheumatoid arthritis (RA) patients without interstitial lung disease (ILD, Group 1) and 14 RA patients with clinical ILD (Group 2) in comparison with 10 control subjects. AM after recovery by bronchoalveolar lavage were selected by adherence, and then supernatants were collected after 3 or 24 h of culture. Results showed no modification of IL-1 synthesis in either group of RA patients. Spontaneous TNF production was significantly increased in Group 2 (2.5 +/- 0.5 ng/ml) as well as in Group 1 (2.4 +/- 0.4 ng/ml) compared with control subjects (0.43 +/- 0.1 ng/ml, p less than 0.001). In addition, AM from patients untreated or treated exclusively by nonsteroidal antiinflammatory drugs produced similar levels of TNF, whereas those receiving corticosteroids, second-line drugs (such as sulfasalazine, aurothiomalate, and methotrexate), or the combination of both therapy regimens released significantly less TNF. Interestingly, TNF was not different in both groups, but Group 2 had a markedly increased ratio of local immune complex to albumin in bronchoalveolar lavage fluid (0.47 +/- 0.12 versus 0.07 +/- 0.02 in Group 1; p less than 0.002). TNF thus appears an additional component of RA subclinical alveolitis in RA, but its prognostic value and its precise role in lung damage remain to be determined. Development of ILD requires certainly complex interactions of synergistic factors, possibly including local immune complexes detected in BAL fluids. | |
| 2261732 | Methotrexate therapy in rheumatoid arthritis. A two year prospective follow-up. | 1990 Sep | One hundred and thirty seven rheumatoid arthritis (RA) patients refractory to D-penicillamine and some of them (15%) refractory to other slow active drugs were treated with oral methotrexate (MTX) (10-15 mg weekly). After 12-24 months of treatment, 94 and 74 patients respectively showed a significant improvement as judged by duration of morning stiffness (p less than 0.0001), grip strength (p less than 0.0001), degree of joint swelling (p less than 0.01) and tenderness (p less than 0.0001) compared to pre-treatment values. This clinical improvement was also associated with a decrease of erythrocyte sedimentation rate (p less than 0.001), decrease of C-reactive protein (p less than 0.0001) and with improvement of anaemia (p less than 0.05). No changes were seen in rheumatoid factor titres. Seventy-four of the patients were followed for up to 24 months. Thirty-one of them (23%) had complete remission and 43 (31%) had an excellent response. Adverse drug reaction during MTX therapy included: elevated liver enzymes in 34 patients, mucosal ulcers in 21, nausea and vomiting in 8, diarrhoea in 4, leukopenia in 2, interstitial pneumonitis in one, intestinal bleeding in one and finally septic arthritis in another patient. The majority of these side effects were resolved without sequelae. However, 15 patients (11%) with adverse drug reactions had to discontinue the treatment. Forty-one of our patients who received a cumulative mean dose of MTX of 1550.5 +/- 235.5 mg underwent a percutaneous liver biopsy. Ten patients had normal tissue, 12 had minimal changes, 13 nonspecific changes and 6 patients had mild fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3624579 | Low-dose methotrexate therapy for cutaneous vasculitis of rheumatoid arthritis. | 1987 Aug | A patient with classic rheumatoid arthritis who developed leukocytoclastic vasculitis is described. Low-dose methotrexate produced prompt healing of the skin lesions. After discontinuation of methotrexate, the lesions recurred, with resolution after a second course of the drug. Methotrexate may be useful in the treatment of cutaneous vasculitis associated with rheumatoid arthritis. | |
| 1857811 | [Pleuro-pulmonary manifestations of rheumatoid polyarthritis]. | 1991 | Sensitive investigations such as pulmonary function tests, broncho-alveolar lavage or computered tomography at high resolution enable pleuro-pulmonary disease to be detected in nearly 50% of those patients studied who had rheumatoid arthritis (PR). The prevalence of these manifestations is most usually elevated in male PR sufferers, those who are sero-positive or have associated extra-articular signs such as sub cutaneous nodules. More recently there has been evidence of genetic risk factors linked to HLA grouping or Pi phenotype. Amongst the usual manifestations, the pleurisies and above all necrobiotic nodules, which are most often asymptomatic, sometimes pose difficult problems in differential diagnosis, particularly when they precede the articular disease. The diffuse interstitial fibrosis remains the most worrying specific complication due to the fact of its potential seriousness. The pathophysiology of this form of fibrosis is better understood since the introduction of LBA. In the absence of any specific controlled studies its treatment remains impirical and is similar to that given for diffuse or idiopathic interstitial fibrosis. Pulmonary vascularity, the bronchiolitis obliterans with organising pneumonia and apical fibrosis, very similar to Hamilton's syndrome, are much rarer manifestations. On the other hand non specific respiratory infections are the cause of death in 10-20% of cases. Bronchiolitis obliterans induced by D Penicillamine is the most severe iatrogenic manifestation, since corticosteroid therapy associated with immunosuppressive drugs enables at best a stabilisation of the alveo bronchiolar lesions. More recently there have been twenty observations of hypersensitivity pneumonia to low dose methotrexate. The prevalence of these pulmonary disorders during the treatment of PR is around 5%. However the respiratory contraindications of these drugs which are being used more and more and the methods of pulmonary surveillance under treatment are not yet defined. | |
| 3499154 | 2,000-centiGray total lymphoid irradiation for refractory rheumatoid arthritis. | 1987 Sep | Because toxicity with the use of 3,000 centiGray (cGy) of total lymphoid irradiation (TLI) was observed in an earlier study, 2,000-cGy treatments were delivered in a 2-portal format to 7 patients and in a modified 3-portal fashion to 6 patients, as part of a randomized, investigator-blinded trial of TLI treatment for refractory rheumatoid arthritis. Analysis of combined data from the 13 patients revealed statistically significant improvement in 5 clinical indicators of disease activity at the end of TLI and 6 and 12 months later, accompanied by T4-specific immunosuppression. Management considerations resulted in the introduction of prednisone therapy in 5 patients, methotrexate in 4, and azathioprine in 1 during the interval of 8-12 months post-TLI. Herpes zoster occurred in 5 patients prior to the initiation of this additional therapy. These data indicate that, in patients with rheumatoid arthritis, a TLI dose of 2,000 cGy is sufficient to produce measurable benefit that lasts for 6 months, and that the improvement can be maintained at 12 months by the use of prednisone and methotrexate. | |
| 3688672 | Pulse methotrexate therapy in rheumatoid arthritis. A controlled prospective roentgenograp | 1987 Dec | STUDY OBJECTIVE: To assess whether weekly pulse methotrexate therapy alters radiographic progression of joint disease in patients with rheumatoid arthritis. DESIGN: Prospective, controlled study. Hand, wrist and foot roentgenograms obtained before, at the onset of, and during methotrexate treatment were scored for degree of joint-space narrowing and erosions by three rheumatologists using a standard method. PATIENTS: Sequential sample of 24 patients with active definite or classical rheumatoid arthritis and previous unsuccessful treatment; of these, 3 were excluded due to drug ineffectiveness; 2, due to side effects; and 1, due to refusal to take methotrexate. INTERVENTIONS: Treatment with nonsteroidal anti-inflammatory drugs and prednisone was continued. Methotrexate was given weekly to control clinical evidence of disease in patients. MEASUREMENTS AND MAIN RESULTS: After having had an average of 30 months of therapy, the 18 patients who continued to receive methotrexate therapy showed significant (p less than 0.05) clinical improvement, as evidenced by their decreased joint counts and joint scores, duration of morning stiffness, pain scales, and sedimentation rates. Despite patients' prolonged clinical improvement, the mean rate of development of erosions and joint-space narrowing during methotrexate therapy was not significantly different from the rate of radiographic progression before methotrexate therapy (0.043 compared with 0.041; p greater than 0.05). CONCLUSIONS: Weekly pulse methotrexate is effective for the long-term management of clinical disease activity in patients with refractory rheumatoid arthritis but may not be a disease-modifying agent by roentgenographic criteria. | |
| 2245532 | Immunological treatment of rheumatoid arthritis. | 1990 Jul | Till now the therapeutic immunomodulation of rheumatoid arthritis (RA) has been non-specific, using either slow acting drugs which act mainly but not exclusively on macrophages (gold salts) or on T CD4+ cells (D penicillamine), or immunostimulating agents (Levamisole) or immunodepressive drugs which do not affect a specific subpopulation of lymphocytes. Various other therapeutic approaches such as dietic manipulations, steroid pulses and plasmapheresis have been proposed. Methotrexate is a very interesting development in the treatment of RA. However, the results of such treatments on the long term outcome of the disease have been unsatisfactory. Early and associated treatments must be studied. After the interesting experimental results obtained with thoracic duct drainage, a partially specific immunotherapy acting mainly on CD4+ T cells has been developed using cyclosporin A and total lymphoid irradiation. However, a more specific immunotherapy of RA may be considered, using monoclonal or polyclonal anti-HLA class II antibodies or anti-CD4 monoclonal antibodies. Immunomodulating treatments with cytokines or anticytokines, anti-T receptor monoclonal antibodies, anti-idiotypic antibodies, and vaccination with T cell clones or synthetic peptides are possibilities of major interest for the future. | |
| 3363283 | Inhibition of neutrophil chemotaxis in methotrexate-treated rheumatoid arthritis patients. | 1988 | Polymorphonuclear cell (PMN) chemotaxis was assessed using the in vitro under agarose assay in ten rheumatoid arthritis patients prior to and following a single 10-mg dose of methotrexate (MTX). PMNs obtained from patients after MTX showed a decreased chemotactic migration response to both zymosan activated serum (P less than 0.005) and N-formyl-L-methionyl-L-phenylalanine (P less than 0.01). In similar conditions, no significant difference in chemotactic migration could be detected in six rheumatoid arthritis patients not on MTX. In contrast to the in vivo effects of MTX, there was no inhibition of normal PMN chemotactic migration following a 30-min in vitro incubation of the cells with MTX (P less than 0.99). | |
| 2068577 | Long-term methotrexate therapy for rheumatoid arthritis. | 1991 Apr | A retrospective review of methotrexate (MTX) treatment assessed the clinical course in 124 rheumatoid arthritis (RA) patients. After 5 years, 39 (31%) patients continued MTX with clinical benefit. Although patients continuing MTX after 5 years were younger (45 +/- 13 v 54 +/- 12 yrs, P less than .001) and had a shorter disease duration of RA (9.3 +/- 8.1 v 14 +/- 11 yrs, P less than .05) than patients who discontinue the drug, these differences were not considered clinically significant. MTX was discontinued in 20 patients for a lack of clinical benefit, in 21 patients for non-drug-related reasons, and in 44 patients for suspected adverse drug reactions. The adverse drug reactions requiring permanent discontinuation of MTX were nausea, stomatitis, hair loss, rash, pulmonary reactions, elevated liver enzymes, hematologic abnormalities, and hepatic fibrosis. At least one adverse drug reaction was reported by 115 (93%) patients receiving MTX, but the majority did not require permanent drug discontinuation. Although the prevalence of adverse reactions increased with longer duration of therapy, no differences existed in the type of reactions reported over 5 years of treatment. There were no risk factors identified that were clearly associated with the development of toxicity. Long-term therapy was primarily limited by adverse reactions rather than loss of efficacy. | |
| 1906935 | A double blind randomized parallel trial of intramuscular methotrexate and gold sodium thi | 1991 Mar | In a double blind study 57 patients with active erosive rheumatoid arthritis without malalignment or deformities (median disease duration 13 months) were randomly treated with 50 mg gold sodium thiomalate (GSTM) or 15 mg methotrexate (MTX) intramuscularly for 6 months. In the GSTM group, 5/28 patients had to be withdrawn because of side effects; in 2/28 the dose was reduced. In the MTX group, 2/29 were withdrawn, one was lost to followup. The number of swollen joints improved by over 6 in 18/26 (MTX) and in 15/21 (GSTM). Five clinical variables and the sedimentation rate improved significantly in both groups without significant intergroup differences. The radiographs of hands, wrists and forefeet (32 joints evaluated according to Larsen) showed a radiological progression in 11/26 (MTX) and in 8/20 patients (GSTM); however, the deterioration of the mean Larsen index was not significant. While there was no significant difference in effectivity, tolerability was better in the MTX group. | |
| 3723494 | Measures of immunologic and inflammatory responses in vitro in rheumatoid patients treated | 1986 Apr | We examined the effects of low dose parenteral methotrexate (MTX) on immunologic and inflammatory responses of potential importance in the pathogenesis of rheumatoid arthritis. Only 2 significant changes were noted: the number of esterase positive cells in the peripheral blood decreased, and the uptake of tritiated thymidine by incubated peripheral blood mononuclear cells fell markedly. These changes were present 48 h after an injection of MTX, before decreased disease activity became clinically apparent. We therefore conclude that they were direct effects of the drug itself. | |
| 1715157 | Hepatic methotrexate content and progression of hepatic fibrosis: preliminary findings. | 1991 Jul | Liver tissue from 16 patients with rheumatoid arthritis was studied. The patients had received low dose methotrexate weekly for a minimum of 12 months between two liver biopsies. The progression of pericellular fibrosis was measured by computerised image analysis. Extracts of these liver biopsy specimens were pooled into five samples according to the progression of hepatic fibrosis and analysed by high performance liquid chromatography. The concentrations of methotrexate, 2,4 diamino-N(10)-methylpteroic acid, and methotrexate polyglutamate were markedly increased in the samples obtained from the three patients who recorded the greatest increase in fibrosis. These preliminary data suggest that progression of hepatic fibrosis is related to the retention of methotrexate and metabolites in the liver. | |
| 2404483 | Methotrexate in rheumatoid arthritis. Impact on quality of life assessed by traditional st | 1990 Jan | In a double-blind, randomized trial of methotrexate vs placebo in rheumatoid arthritis, the effect of treatment on physical, social, and emotional function was measured in two different ways: the same, standard measurements in all patients, and individualized measurements selected by the patients at the start of the trial as representing the functions they most wanted to have improved by treatment. On the standard measurements, methotrexate-treated patients fared better than placebo-treated patients in their physical, social, and emotional function by 11%, 5%, and 6%, respectively, results that, although statistically significant, were small. However, methotrexate-treated patients were 29% better in the individualized measures, a result that was both highly statistically significant and greater than the differences in the standard measurements or in joint counts, grip strength, proximal interphalangeal joint circumference, morning stiffness, or walking time. Because the individualized measurements were as efficient as the best direct joint examination measures, yet reflected functional outcomes of greatest importance to individual patients, they constitute useful measures for such trials. |