Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7979919 | Detailed immunohistologic evaluation of a methotrexate-induced nodule. | 1994 Dec | Accelerated nodulosis in patients with rheumatoid arthritis who are receiving methotrexate has become a well-recognized phenomenon, and it appears to occur in both individuals with seropositive and seronegative findings. No histologic differences permit a distinction between seronegative and seropositive nodulosis--either occurring during the natural history of rheumatoid arthritis or when "induced" by methotrexate. We examined such a nodule in a man with seronegative rheumatoid arthritis. Results of immunofluorescence examination were not contributory, but studies of the inflammatory cell populations within the nodule showed 5% of the cells to be lymphocytes with a CD4/CD8 ratio of 25:1. Of the total mononuclear cells, 85% were reactive for Leu-10 (HLA-DQ) and 95% were reactive for HLA-DR, and about 75% of the macrophages were reactive for CD4+. The strong expression of CD4, in conjunction with macrophage markers, and the high T-helper/suppression ratio are of note. We discuss the implications of these findings and the role that they play in the pathogenesis of methotrexate-induced nodules. | |
| 1455372 | [The efficacy of basic therapy in rheumatoid arthritis with methotrexate]. | 1992 | Overall 25 patients with rheumatoid arthritis received methotrexate as basic therapy in a weekly dose of 7.5 mg. The patients were followed up for a year. The control examinations were carried out every three months. The therapeutic effect was evaluated from the dynamics of 10 clinical and laboratory parameters. The efficacy of methotrexate treatment provided for a year turned out as follows: significant improvement was attained in 11 patients, improvement was recorded in 9; no changes were demonstrated by 5 patients. Thus, the positive effect was attained in 20 patients (80%). A clinical remission was recorded in 4 patients. Small doses of methotrexate were tolerated well. During one year, the drug was discontinued in none of the patients. Mild side effects were noticed in 11 patients. The temporary drug withdrawal made it possible to continue treating those patients. The majority of the humoral immunity tests showed positive dynamics. As for the titers of rheumatoid factors, such regularity could not be traced. | |
| 9064112 | Pseudo-felty's syndrome. Report of a case with no symptoms for at least 15 years. | 1996 Jan | The prognosis of large granular lymphocyte proliferation with rheumatoid arthritis (pseudo-Felty's syndrome) remains uncertain. We report a case with a 15-year follow-up. To date, the patient has not developed lymphadenopathy, splenomegaly, abnormalities in erythrocyte or platelet counts, neutropenia or severe or unexplained infections. This favorable course is not ascribable to an unusual lymphocyte phenotype (CD3+, CD8+, CD57+). A beneficial effect of methotrexate therapy is possible. | |
| 8833049 | Historical overview of the treatment of rheumatoid arthritis with an emphasis on methotrex | 1996 Mar | We have reviewed the treatment of rheumatoid arthritis (RA) in pertinent selected literature with a focus on methotrexate (MTX). Considerable progress has been made over the last 120 years since the introduction of salicylates to treat rheumatic symptoms. Most slow acting antirheumatic drugs became widely used in the years after the second world war. MTX became widely accepted in the 1980s although early reports of its use predate that time. The historical perspective of the development of agents to treat RA indicates that most significant advances are concentrated in the last 45 years, especially the last 15 years. This trend will likely continue. | |
| 8792795 | Randomized, placebo controlled trial of withdrawal of slow-acting antirheumatic drugs and | 1996 | Patients with rheumatoid arthritis, in stable treatment with methotrexate, penicillamine, or sulfasalazine, were randomized in a double-blind fashion either to continuation of their usual treatment or to placebo. 112 patients were included; 52 patients who refused participation had no more severe disease than the others. The patients felt worse on placebo than on active drug (p = 0.002). The mean differences in number of tender, painful and swollen joints after one month were 2.4 (p = 0.08), 3.0 (p = 0.12) and 2.2 (p = 0.03), respectively. Treatment failure occurred for 42 patients of whom 33 received placebo (p = 0.000,001). There was no difference in the severity of side effects (p = 0.91). The patients guessed their treatment correctly more often than expected (p = 0.02) because of the perceived effect. None of the two observers guessed better than chance, and there were no differences between the observers' evaluations of the joints. The effect of slow-acting antirheumatic drugs was unequivocal and no observer bias occurred. | |
| 1457487 | Sensitivity to change of the health assessment questionnaire (HAQ) and other clinical and | 1992 Sep | To obtain evidence concerning short-term and long-term efficacy of clinical and health status measures in rheumatoid arthritis (RA), we conducted two observational studies--a 6-month study of 233 patients receiving methotrexate and a 10-year study of 157 patients receiving multiple treatments in a rheumatic disease clinic. Results of the 6-month study yielded effect sizes for treatment similar to the meta-analyses reported by Felson [corrected] et al. (Arthritis Rheum 33:1449-1461, 1990) and the controlled trials of methotrexate reported by Weinblatt et al. (Arthritis Rheum 33:330-338, 1990), suggesting that observational studies provide valid measurements of treatment effect. The effect size for the Health Assessment Questionnaire (HAQ) was 0.5. By contrast, the 10-year study suggested that standard clinical variables changed little and were not useful in assessing RA outcome, while the effect size of the HAQ was -2.39. These data continue to underscore the differences between short-term trials and the long-term outcome of RA, and suggest an important place for the HAQ or similar instruments in all phases of RA evaluation and assessment. | |
| 8731236 | How do French rheumatologists treat early rheumatoid arthritis? | 1996 Mar | Although factors that appear to predict long-term outcomes of rheumatoid arthritis have been identified, there is no consensus about the treatment early in the disease. To determine how French office- and hospital-based rheumatologists treat early rheumatoid arthritis, we created three clinical vignettes corresponding to different levels of severity of early rheumatoid arthritis (less than six months' disease duration). Cases 1 and 2 were relatively young patients (35 and 50 years), and Case 1 had numerous poor prognosis factors. Case 3 was 80 years of age. Rheumatologists were asked to indicate which medications they would use at presentation and after one year of a favorable or unfavorable course. The study was conducted by questionnaire (response rate, 58%). Of the 185 rheumatologists who completed the questionnaire, 81% were male and 19% female; mean age was 42 +/- 8 years. In Cases 1 and 2, nonsteroidal antiinflammatory drugs were given by 99% of respondents; second-line drugs were prescribed at presentation by 93% of respondents in Case 1 and 86% in Case 2, and methotrexate was more likely to be used in the presence of poor prognosis factors (23% in case 1 and 7% in Case 2). In the event of an unfavorable course after one year, a larger proportion of rheumatologists prescribed glucocorticoid therapy (65% in Case 1 and 20% in Case 2), and there was a shift from "conventional" to "modern" second-line drugs, with more widespread use of methotrexate (65% in case 1 and 18% in case 2). In the 80-year-old patient, glucocorticoid therapy was used more often than nonsteroidal antiinflammatory drugs and second-line drugs (gold salts, hydroxychloroquine, sulfasalazine) were prescribed by 40% of rheumatologists at presentation and by 67% after one year of an unfavorable course; in the latter situation, methotrexate was selected in 24% of cases. In contrast to conventional recommendations, many French office- or hospital-based rheumatologists use second-line drugs very early and base their choice of medications on the estimated risk of severe disease and on the age of the patient. | |
| 8489539 | The effects of drug therapy on radiographic progression of rheumatoid arthritis. Results o | 1993 May | OBJECTIVE: To determine the effects of drug therapy (methotrexate [MTX] versus auranofin [AUR]) on radiographic progression in patients with active rheumatoid arthritis (RA). METHODS: We conducted a 9-month randomized, multicenter, double-blind trial comparing MTX and AUR. Standardized radiographs of the hands and wrists were obtained at baseline and at completion of the study. Four experienced bone radiologists graded the radiographs for erosions, joint space narrowing, erosion healing, and reparative bone formation. RESULTS: Two hundred eighty-one patients were enrolled in the study. Radiographs were available on 167 of the 183 who completed the trial. After 9 months of therapy, there was a significantly greater worsening of the erosion score in the AUR group (mean +/- SEM change of 1.67 +/- 0.4) compared with the change in the MTX group (0.60 +/- 0.3) (P = 0.040). There was also a significantly greater worsening of the joint space narrowing score in the AUR group compared with the MTX group (1.36 +/- 0.3 versus 0.42 +/- 0.2) (P = 0.007). There was no difference demonstrated between groups in healing of erosions or in reparative bone formation. CONCLUSION: The rate of radiographic progression in patients with RA, as measured by erosion score and joint space narrowing score, was demonstrated to be lower in those treated with MTX, as compared with AUR, over a 36-week period. | |
| 8258236 | One year treatment with low dose methotrexate in rheumatoid arthritis: effect on class spe | 1993 Sep | We evaluated the effect of a one-year treatment of low dose methotrexate (MTX) on class specific rheumatoid factors in 27 patients with rheumatoid arthritis (RA). Enzyme-linked immunosorbent assay (ELISA) showed after 6 and 12 months a significant reduction of IgM-RF, IgA-RF and IgG-RF levels from the baseline values. During MTX treatment, changes of each RF isotype were not correlated with any other isotype and its corresponding immunoglobulin changes. Moreover, immunological changes were not related to the improvement of clinical parameters. Our results showed that low dose MTX can specifically affect levels of RF isotypes, which are involved in the immune pathogenesis of RA. | |
| 1290480 | Successful reintroduction of methotrexate after pneumonitis in two patients with rheumatoi | 1992 Feb | Two patients are described with severe and progressive rheumatoid arthritis in whom methotrexate was reintroduced despite previous methotrexate related pneumonitis. In both patients a marked improvement in disease control occurred without a recurrence of the pneumonitis. | |
| 8371204 | Influence of methotrexate on the frequency of postoperative infectious complications in pa | 1993 Jul | OBJECTIVE: To evaluate the influence of methotrexate (MTX) on the frequency of postoperative complications in patients with rheumatoid arthritis (RA). METHODS: We conducted a randomized unblinded prospective study in 64 patients with RA treated with MTX and who underwent orthopedic surgery. Two groups of patients were constituted: in Group A (32 patients), MTX was interrupted 7 days before the surgery; in Group B (32 patients), MTX was not discontinued. RESULTS: Fifty surgical procedures were performed in Group A and 39 procedures in Group B. No postoperative infection was observed in any group. A prolonged wound healing was noticed in 6 cases in Group A and in 4 cases in Group B (not significant). CONCLUSION: We suggest that the interruption of MTX is not required in patients with RA when an orthopedic surgical treatment is planned. However a large prospective study is needed to make a definitive conclusion. | |
| 8882028 | The frequency of cutaneous vasculitis is not increased in patients with rheumatoid arthrit | 1996 Feb | OBJECTIVE: To analyse the frequency, type, and immunohistological features of clinical cutaneous vasculitis developing in patients with rheumatoid arthritis (RA) treated or not with methotrexate as well as their demographic, clinical and biological characteristics. METHODS: Ninety-one patients with RA receiving 9.5 mg/wk of methotrexate (MTX) were compared for an average observation time of 18 months to 130 matched patients with RA treated with various drugs excluding MTX. RESULTS: Whether receiving MTX or not, 5.4% of patients with RA developed a clinical cutaneous vasculitis. There were significant differences between both groups for 2 variables only: a higher percentage of polyneuropathies and a higher level of immune complex-plasma levels in non-MTX patients. The immunohistological analysis did not differentiate both groups. CONCLUSION: The percentage of cutaneous vasculitis that developed under MTX therapy was not different from that occurring as a natural complication of longstanding severe RA. | |
| 8685145 | [Combination regimens in rheumatoid arthritis]. | 1996 Jun 1 | The objective of combination regimens in the treatment of rheumatoid arthritis is to improve effectiveness (additive or synergistic effect) and reduce the rate of side effects. Many combinations have been tried. In general, compared with single-drug regimens, combination therapy does not increase toxicity but clinical improvement has not been proven. In addition, there is no evidence concerning the long-term effects of combination regimens. Despite these drawbacks, combining drugs known to be effective in rheumatoid arthritis alone may be an interesting alternative for patients who have responded incompletely to single drugs, particularly methotrexate. However, for both single-drug and combination regimens we are still lacking proof of a real beneficial effect in terms of reducing functional impairment, improving quality of life, lengthening life expectancy, or reducing overmortality resulting from rheumatoid arthritis. Long-term outcome may provide some answers. Finally, there are still several combinations to be studied including methotrexate with "targeted" drugs such as anti-CD4 and anti-TNF alpha antibodies or the soluble TNF alpha receptor. | |
| 1613728 | Mechanisms of action of disease modifying antirheumatic drugs. | 1992 Jan | The relationship between the biologic activities of disease modifying antirheumatic drugs (DMARD) and their therapeutic effects are complex. Some DMARD are prodrugs, e.g., azathioprine; others may act in combination with endogenous substances, e.g., D-penicillamine and copper salts. Gold compounds, antimalarials, sulfasalazine, azathioprine and methotrexate affect various phagocytic cell functions. Most DMARD inhibit the immune responses of monocytes and of T and B lymphocytes. Gold, sulfasalazine, D-penicillamine also affect fibroblast and/or endothelial cell proliferation. Many DMARD inhibit responses to, or production of, cytokines. Several DMARD have overlapping biologic effects but differ in their therapeutic efficacy in individual patients for unknown reasons. | |
| 1734901 | Long-term prospective study of methotrexate in the treatment of rheumatoid arthritis. 84-m | 1992 Feb | OBJECTIVE: To determine the long-term efficacy and safety of low-dose methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Eighty-four-month open prospective trial at a single academic rheumatology center. RESULTS: Twenty-six patients were enrolled in a prospective study of the long-term efficacy of MTX in RA; a significant improvement had been demonstrated after 36 months of therapy. Twelve patients remained in the study at the 84-month visit; the mean weekly dosage of MTX was 10.2 mg. A significant improvement was still noted at 84 months in the number of painful joints, number of swollen joints, joint pain index, joint swelling index, and physician and patient global assessments. A 50% improvement in the joint pain index and joint swelling index was observed in more than 80% of the 12 patients still enrolled. A significant reduction in prednisone dosage was achieved; of 14 patients taking prednisone at entry, 7 had discontinued prednisone completely. Fourteen patients withdrew from the study: 10 between 0 and 36 months, and 4 between 36 and 84 months. Toxicity in 3 patients and visit noncompliance in 1 patient were the reasons for withdrawal between 36 and 84 months. At 84 months, 46% of the patients remained in the study; 11.5% had discontinued due to MTX toxicity. CONCLUSION: The effectiveness of MTX in the treatment of RA continues to be demonstrated in this prospective study, after 84 months of treatment. | |
| 1412121 | Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis | 1992 Aug | BACKGROUND: Low dose methotrexate has become established in the treatment of refractory rheumatoid arthritis. Until recently it has been considered that the use of a low dose regimen (< 20 mg/week) would avoid the pulmonary toxicity associated with the higher doses prescribed in malignant disease. Although initial experience with low dose methotrexate was encouraging, an increasing number of cases of an acute, life threatening pneumonitis are being reported in patients with refractory rheumatoid arthritis. PATIENTS: Since 1984 43 patients with refractory rheumatoid arthritis have been established on low dose methotrexate in the Oxford Health District. Five of these patients have subsequently developed acute methotrexate induced pneumonitis. The clinical and radiological features of these cases are described and previous reports reviewed. RESULTS: Five patients having low dose methotrexate treatment developed acute pneumonitis. Presentation was subacute and dominated by constitutional features. Respiratory symptoms developed insidiously but progressed rapidly with increasing dyspnoea associated with severe hypoxia. Chest radiographs were non-specific, showing diffuse interstitial infiltration and alveolar shadowing. Microbiological investigation gave negative results. In all cases methotrexate was discontinued and high dose corticosteroids started, with rapid clinical and radiological improvement. After withdrawal of steroid both clinical and radiological resolution was maintained at follow up. CONCLUSION: Acute pneumonitis is an uncommon but serious adverse effect of low dose methotrexate treatment for refractory rheumatoid arthritis. The initial presentation is non-specific and a high index of suspicion is required as respiratory failure may develop rapidly. Management depends on exclusion of infection, withdrawal of methotrexate, and high dose corticosteroid treatment. Full supportive treatment is indicated as the prognosis in such patients is good. | |
| 1290023 | Osteocalcin in patients with rheumatoid arthritis--effect of anatomical stages, inflammato | 1992 | The aim of this study was to investigate whether the degree of inflammatory activity, the anatomical stage and various treatments have an influence on bone turnover in patients with rheumatoid arthritis (RA). Osteocalcin (OC) and other parameters of bone turnover were measured in 131 patients with RA. The mean values of alkaline phosphatase (AP), but not of OC were significantly (P < 0.01) higher in our patients compared to controls. In contrast to AP, OC values increased and correlated significantly (r = +0.33, P < 0.01) with ascending anatomical stage in women not on glucocorticoid treatment. As regards therapy, we found significantly lower OC levels in women receiving steroids compared to controls (P < 0.03) and those being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (P < 0.03), methotrexate (MTX) (P < 0.05), or gold (P < 0.01). Females treated with gold had higher OC levels than patients receiving no antirheumatic drugs (P < 0.03). Furthermore, there was a significantly negative correlation between OC and inflammatory activity [C-reactive protein (CRP)] (r = -0.25, P < 0.003). In conclusion, OC levels were significantly higher (P < 0.032) in patients with advanced (anatomical) stages of RA. In contrast to AP, changes in bone turnover, such as suppression of bone formation by steroids and high inflammatory activity in patients with RA, were easily detected. | |
| 7586778 | Correlation between methotrexate pharmacokinetic parameters, and clinical and biological s | 1995 Jul | OBJECTIVE: To determine the correlation between the pharmacokinetic (PK) parameters of methotrexate (MTX), clinical status and laboratory test results in rheumatoid arthritis (RA) patients. METHODS: 22 patients (4 M/18F, mean age: 50 +/- 12 years, mean duration of RA: 8.5 +/- 6.5 years, mean duration on MTX: 8 +/- 10 months) were included in a prospective study. The mean dose of MTX administered was 6 +/- 0.7 mg/m2 of body area/week. No patient received any nonsteroidal antiinflammatory drug (NSAID). Blood and urine samples were collected over 24 hours (9 blood samples). The MTX concentrations were assayed by fluorescence polarization immunoassay. Clinical parameters (Ritchie articular index, morning stiffness, joint pain count, joint swelling count), hematological, liver and renal function tests, and ESR were recorded. Correlations between the patients' PK parameters, laboratory tests and clinical status were carried out using Pearson's correlation coefficient test. RESULTS: A significant correlation was observed between the Ritchie articular index, morning stiffness and the area under the curve (p = 0.009 and p = 0.026, respectively). No correlation was found with the other parameters. CONCLUSION: These results suggest that when the patient's disease activity is higher, the AUC becomes more important, reflecting a greater body exposure to MTX. | |
| 7985038 | Posterior interosseous nerve entrapment in rheumatoid arthritis. | 1994 Aug | Posterior interosseous nerve (PIN) entrapment is a rare complication of rheumatoid arthritis (RA) which, together with extensor tendon rupture and metacarpophangeal joint dislocation, should be considered in the differential diagnosis of inability to extend the fingers. The inability to extend the thumb in PIN entrapment is a useful distinguishing clue on physical examination, and nerve conduction studies confirm the diagnosis. Elbow joint swelling and compression of the PIN at the arcade of Frohse are the main reasons for PIN entrapment in RA. Intraarticular steroid injections and surgical intervention resolve symptoms of PIN entrapment in RA. In our case, the addition of methotrexate, which induces a rapid antiinflammatory effect, resulted in resolution of weakness with complete recovery in the extensor muscles of the fingers. | |
| 7851956 | Associations of IgA and IgA-rheumatoid factor with disease features in patients with rheum | 1994 Nov | In previous studies we have shown that levels of IgM-rheumatoid factor (RF) in plasma and peripheral blood mononuclear cell supernatants are correlated with disease activity and response to second-line therapy in patients with rheumatoid arthritis (RA). The present studies were designed to examine whether IgA-RF levels are also correlated with clinical features of this disease. Two groups of RA patients were studied. Group I consisted of 87 patients in whom extensive clinical data had been collected. Group II included nine patients beginning treatment with gold or methotrexate who were studied during the first year of therapy. Measurement of IgM, IgA, IgM-RF and IgA-RF in culture supernatants and plasma was done by an ELISA method. These data were examined for correlations with clinical and laboratory features. Levels of IgA-RF in supernatants and plasma were found not to be correlated with disease features in the cross-sectional analysis of Group I patients, while IgM-RF and total IgA levels did show significant clinical correlation. Treatment of Group II patients with gold or methotrexate was associated with significant decreases in plasma levels of total IgA and IgM-RF as well as a small but statistically significant decrease in plasma IgA-RF. Plasma levels of total IgM were not altered during therapy. These findings suggest that production of IgA but not IgA-RF is correlated with disease status in patients with RA. |