Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8864579 | Management of spondyloarthropathies. | 1996 Jul | Better understanding of the etiopathogenic mechanisms and increasing recognition of the natural course of the spondyloarthropathies are leading to a more rational therapeutic approach to several of the disorders included within this large group of arthritides. Our traditional therapeutic approach to these conditions is being challenged, and a more aggressive therapeutic regimen is being advocated in a manner not too much different from that advocated for the treatment of rheumatoid arthritis. Combination therapy with either methotrexate and sulfasalazine or methotrexate and cyclosporine is being used more often and earlier, particularly in psoriatic arthritis. An issue, however, that remains unresolved is the proper use of antibiotic therapy. | |
| 7944621 | Serial measurements of soluble interleukin 2 receptor levels (sIL2-R) in children with juv | 1994 Jul | OBJECTIVE: To investigate the potential clinical utility of serial levels of sIL2-R as a marker of disease activity among children with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). METHODS: sIL2-R levels, measured by ELISA, were evaluated in 16 JRA patients (10 polyarticular, six systemic-onset) treated with oral, weekly MTX. sIL2-R values were compared with those of 49 normal controls. Medical record review was used to obtain relevant clinical data. Joint counts (number of swollen joints) were used as indicators of clinical change. A reduction of 50% in joint counts between pre and post treatment measurements was considered a clinically significant response. RESULTS: The mean (SEM) sIL2-R value of pre treatment JRA of 1728(290) U/ml was significantly higher than the post treatment value of 921(229) U/ml (Wilcoxon Rank test, p < or = 0.001). Pre treatment values were also significantly different from the mean(SEM) of healthy controls of 519(19) U/ml (p < 0.001). Pre treatment sIL2-R levels of 2417(291) U/ml in systemic-onset JRA were significantly higher than sIL2-R values in polyarticular JRA patients of 1218(884) U/ml (Mann-Whitney rank test p < 0.001). Among the 13/16 children with good therapeutic responses (> or = 50% improved), the range of sIL2-R decreases was 154-2641 U/ml (mean 842 U/ml); sIL2-R levels increased in the three children with poor clinical responses to methotrexate. CONCLUSIONS: sIL2-R levels paralleled the course of disease in all patients. sIL2-R levels may be useful for monitoring therapeutic responses in children with JRA. | |
| 8235664 | Comparative efficacy and safety of advanced drug therapy in children with juvenile rheumat | 1993 Aug | Results from three randomized placebo-controlled trials were combined in a meta-analysis to compare the clinical utility of four advanced drug therapy agents used to treat juvenile rheumatoid arthritis (JRA): D-penicillamine (10 mg/kg/d), hydroxychloroquine (6 mg/kg/d), auranofin (oral gold, 0.15 to 0.20 mg/kg/d), and two low dose levels of methotrexate [5MTX, 5 mg/M2/wk; 10MTX, 10 mg/M2/wk]. A total of 520 children with JRA were enrolled into these trials. Only 10MTX resulted in significantly greater improvement than placebo in variables that assess effectiveness: physician's global assessment, a composite index, and erythrocyte sedimentation rate. Treatment effect sizes were the largest in the 10MTX group for all articular disease indices. The short-term safety profiles were similar across all treatment groups. It is concluded that the current trend among pediatric rheumatologists to use oral methotrexate as the first advanced drug therapy in JRA is appropriate and that the minimum effective dose is 10 mg/M2/wk. | |
| 1593584 | Repetitive use of pulse therapy with methylprednisolone and cyclophosphamide in addition t | 1992 Apr | Patients with systemic juvenile rheumatoid arthritis (JRA) are often poorly responsive to existing therapeutic modalities. We evaluated the effectiveness of pulse therapy consisting of methylprednisolone 30 mg/kg/day for 3 consecutive days combined with cyclophosphamide 0.4 g/m2 body surface area on the 3rd day, for 18 patients with definite systemic JRA, who were enrolled in an open trial of 12 months' duration. The children received pulse therapy every 3 months; oral methotrexate 10 mg/m2 was started after the first pulse. A rapid and clinically significant suppression of systemic and articular manifestations was seen in all patients. Significant decreases in laboratory indices of disease activity were also observed. Side effects were minor and reversible. The results of our preliminary trial support the development of a controlled study to evaluate the efficacy of pulse therapy in systemic JRA. | |
| 8164218 | Plasma levels after oral methotrexate in children with juvenile rheumatoid arthritis. | 1993 Sep | Plasma levels of methotrexate (MTX) after oral administration of 6.4 to 11.2 mg/m2/week (mean 8.5 mg/m2/week) were studied in 33 children with severe juvenile rheumatoid arthritis (JRA). MTX concentrations were measured by a fluorescence polarization immunoassay (TDx) at 1, 2, 3, and 24 h after administration. The maximum level was observed in most patients after 1 h. No significant correlation was found between MTX dosage and the 1, 2, and 3-h plasma levels. No patient showed values in the range of probable toxicity 24 h after administration. A stepwise multiple regression analysis on 1, 2, and 3-h MTX levels, selected clinical features, dosage and duration of MTX therapy, and concomitant drug treatment showed that MTX concentrations at the different time points tend to be closely related; among the other variables, only concurrent treatment with salicylates was found to affect significantly the 3-h level. Serial determinations performed in 20 patients at the same oral dosage showed a wide interindividual and intraindividual variability of the plasma levels from the first dose to the next. Variable and unpredictable levels were observed also in most of the 8 patients studied after one or more increases of MTX dosage. No difference in MTX concentrations was observed between patients who responded to treatment and those who failed to respond, and between patients who had serum transaminase elevation and those who did not. Our results suggest that, until the pharmacokinetics of low dose MTX is clarified, routine therapeutic monitoring of MTX has a limited value in the clinical management of children with JRA. | |
| 1377772 | [Therapy of juvenile rheumatoid arthritis]. | 1992 May | The correct drug treatment of JRA must consider the course and the subtype of the disease. Nonsteroidal antiinflammatory drugs are the first choice treatment, especially the recent ones which are more active and less toxic. The slow-acting antirheumatic drugs are the second choice treatment and must be employed in the chronically active stages of the disease; good results have been obtained with sulphasalazine and methotrexate both on clinical features and on blood biochemistry with relatively scarce side effects. Thymic hormones, cyclosporin A and intravenous immunoglobulins, though not yet widely experienced, can represent a worthwhile alternative to standard treatment in carefully selected cases. Steroids must be used only in special cases (particularly aggressive systemic JRA, carditis, severe anemia and those patients who fail to respond to usual treatments) and must be withdrawn as soon as possible to avoid adverse effects and steroid-addiction. Intraarticular long-acting steroids are the first choice treatment for rheumatoid monoarthritis. | |
| 1575789 | Acute iritis associated with primary Sjögren's syndrome and high-titer anti-SS-A/Ro and a | 1992 May | OBJECTIVE: We describe a patient with primary Sjögren's syndrome who developed severe, acute, anterior uveitis (iritis), an uncommon complication in this setting. METHODS: We present the case report of the clinical findings, course, treatment, and resolution of the acute uveitis. Titers of anti-SS-A/Ro and anti-SS-B/La antibodies were assessed (by immunodiffusion), as were fluorescent antinuclear antibodies (on HEp-2 cells) and cryoglobulins. RESULTS: Initial treatment with topical steroids, oral prednisone (20 mg/day), and oral methotrexate was unsuccessful. The iritis resolved after combined treatment with intravenous cyclophosphamide (1,500 mg/month), high-dose prednisone (60 mg/day), and cyclosporine (5 mg/kg/day). CONCLUSION: An uncommon, severe complication of primary Sjögren's syndrome is acute uveitis. Combination immunosuppressive therapy may be needed to control this condition. | |
| 8796975 | Disease-modifying antirheumatic drugs, including methotrexate, gold, sulfasalazine, antima | 1996 May | The class of agents known as disease-modifying antirheumatic drugs remains the predominant treatment for rheumatoid arthritis. Methotrexate has again demonstrated efficacy in long-term studies, and more reports on its pharmacokinetics and possible mechanism of action have been published. Renal impairment has been highlighted again as a major risk factor for methotrexate toxicity, and studies have supported the American College of Rheumatology guidelines concerning elevated transaminases as a warning sign for liver toxicity. Although questions about the long-term efficacy of gold have again been raised, some interesting reports have focused on its mechanism of action. The sulfasalazine literature includes reports on possible immunomodulatory roles for the drug in the gastrointestinal tract. The usefulness of hydroxychloroquine has been confirmed in a large study of early rheumatoid arthritis. The minimal effective dose of D-penicillamine has been questioned in a clinical study. Combination therapy using existing disease-modifying antirheumatic drugs has not demonstrated major benefits over single-drug therapy. | |
| 8099805 | Disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, gold, antima | 1993 May | Rheumatoid arthritis is a progressive inflammatory disease with evidence of early cartilage damage. Consequently, there is a trend toward earlier use of disease-modifying antirheumatic drugs. This review focuses on recent data on methotrexate, sulfasalazine, gold, hydroxychloroquine, D-penicillamine, and combination therapy. Methotrexate is focused on most, reflecting the increasing popularity of this agent; studies continue to show its good clinical efficacy. Combination therapy studies have been disappointing and are still marred by short duration and low power. Sulfasalazine has a fairly rapid onset of clinical effects and modulates immune function. Gold is still the subject of new studies, with evidence that clinical experience leads to improved patient efficacy. The beneficial effect of hydroxychloroquine in mild rheumatoid arthritis has been confirmed, and information on D-penicillamine suggests an effect on oxygen radical scavenging. Clinical studies are still required to ascertain the relative efficacy of these drugs, and potential long-term adverse effects remain a source of concern. | |
| 19078032 | Lymphoma and luekemia in rheumatoid arthritis: are they associated with azathioprine, cycl | 1996 Apr | Incident cases of lymphoma and leukemia in a cohort of 3824 rheumatoid arthritis (RA) patients from the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) database were identified, and the use of azathioprine, cyclophosphamide, and methotrexate was compared in a matched case-control study. Controls were matched on age, sex, year of study entry, disease duration, center, and years of follow-up. Twenty-four cases of lymphoma and 10 cases of leukemia were identified: 21% of patients with cancer versus 9% of controls had taken azathioprine [McNemar statistic 1.50 (p = 0.22), odds ratio 5.0 (95% confidence interval 0.6,236.5)]. Equal numbers of cases and controls (6% each) had taken cyclophosphamide and 18% of cases and 12% of controls had taken methotrexate [McNemar statistic 0.13 (p = 0.72), odds ratio 1.7 (0.3, 10.7)]. Results suggest but do not prove that RA patients taking azathioprine and methotrexate may have an increased risk of developing lymphoma. However, even if this increased risk can be confirmed, it accounts for only a small proportion of the greatly increased incidence of these malignancies in RA. | |
| 19078081 | Medication choices in juvenile rheumatoid arthritis. | 1996 Oct | This survey was performed to review medication usage by pediatric rheumatologists in the care of patients with juvenile rheumatoid arthritis (JRA). Prospective data from 50 patients per physician with JRA were recorded by six pediatric rheumatologists in the Fall of 1993. Naproxen was used most frequently-in 48% of all patients. Next in order of frequency were methotrexate (39%), prednisone (15%), tolmetin (12%), indomethacin (11%) and folic acid (10%). Salicylates (acetylsalicylic acid, trisalicylate and salsalate) were used in 7%, and myochrysine was used in 2% of patients. Overall, nonsteroidal anti-inflammatory drugs were used in 93% of all patients, slower-acting antirheumatic drugs (SAARDs) were used in 54% and prednisone in 15%.Medication usage varied by disease type in predictable ways but also varied by physician in ways that could not be accounted for by population differences. Methotrexate was the most-often used of all SAARDs and supplanted myochrysine in JRA. Naproxen was the most often used NSAID in the treatment of JRA and had largely supplanted salicylates. With the arrival of practice guidelines, reasons for and impact of these changes (as well as the interesting variations between physicians) will need to be examined. | |
| 7955637 | Aggressive treatment in childhood rheumatic diseases. | 1994 Sep | Much remains to be learned about the optimal therapy for children with rheumatic diseases. Current therapies remain inexact and are aimed at either the inflammatory or the immune responses of patients. There have been a few advances, for example in the treatment of children with dermatomyositis, lupus and, in particular, Kawasaki disease. Progress in the treatment of juvenile rheumatoid arthritis (JRA) and the spondylarthropathies has lagged behind, however, although methotrexate does appear to be promising in the short-term treatment of JRA. Another urgent problem which remains to be resolved is the identification of those children who will have poor outcomes and who warrant early, aggressive treatment. A number of interesting alternative therapies for adults have been proposed, but their applicability to children remains an open question. Further investigation of combined therapies with various drugs also warrants exploration. | |
| 8064722 | Methotrexate in systemic lupus erythematosus. | 1994 May | OBJECTIVE: Methotrexate (MTX) has been used successfully in the treatment of rheumatoid arthritis, psoriatic arthritis, polymyositis, and Reiter's syndrome. Our objective was to determine the effectiveness of MTX in the treatment of systemic lupus erythematosus (SLE). METHODS: We reviewed retrospectively MTX therapy in 5 patients with SLE, 3 with renal disease and 2 with arthritis. RESULTS: MTX therapy was well tolerated and effective in all 5 patients. CONCLUSION: MTX appears to be both effective and well tolerated in patients with SLE. | |
| 1460882 | [Still's disease in adults and polymyositis. An infrequent association]. | 1992 Oct 3 | A case of coexistence of adult onset Still's disease and idiopathic inflammatory myopathy is reported in a patient with antecedent of Graves-Basedow disease. Although myalgias are common during the flares of adult onset Still's disease, a review of literature only disclosed two previous cases of polymyositis associated to adult onset Still's disease. A high index of suspicion is needed in order to diagnose such a rare association which has relevant prognostic and therapeutic implications. Treatment with methotrexate was started in order to control myopathy, resulting in improvement of both polymyositis and adult onset Still disease. A possible role of methotrexate in the management of adult onset Still's disease is suggested. | |
| 1543666 | Immunopathology, rheumatic features, and therapy of sarcoidosis. | 1992 Feb | A spectrum of immune alterations underlies the clinical syndrome of sarcoidosis. There is an increase in the number of helper T lymphocytes at sites of disease activity. Both macrophages and T cells are in a state of activation. Inflammation in sarcoidosis probably attracts specific T lymphocytes, as has been shown by the preferential usage of the C beta 1 elements of the T-cell antigen receptor. Acute sarcoid arthritis is distinctly different in its HLA association and clinical outcome than chronic sarcoid arthritis. Muscle and osseous lesions are well described but are usually asymptomatic. Childhood sarcoidosis may be confused with juvenile rheumatoid arthritis because of the similarity of eye and articular involvement. Nonsteroidal anti-inflammatory drugs and corticosteroids are effective for most patients. Hydroxychloroquine, methotrexate, and cyclosporine have been tried with success in patients with refractory sarcoidosis. | |
| 8496877 | Inflammatory arthropathies in children with chromosomal abnormalities. | 1993 Apr | There are few observations of inflammatory synovitis in association with specific chromosomal abnormalities in children or adults. We review the genetic and rheumatic disease literature and describe the clinical, radiologic and pathologic features of a 14-year-old boy with trisomy 5q, terminal 2p deletion, developmental delay, and a 5-year course of a polyarticular, symmetrical arthropathy similar to juvenile rheumatoid arthritis. He was treated with multiple nonsteroidal antiinflammatory drugs, intramuscular gold, and oral methotrexate, but developed iridocyclitis, joint space narrowing with erosions, and multiple flexion contractures; disease progression slowed after addition of chlorambucil. The frequency and manner of association of genetic disorders with inflammatory arthropathies is presently unknown. Additionally, children with 2 major disabilities often require aggressive medical intervention to maximize their potential for adult independence. | |
| 1439846 | Timed treatment of the arthritic diseases: a review and hypothesis. | 1992 Oct | Evidence has been accumulating regarding the importance of biological rhythms in the diagnosis and treatment of a variety of diseases and disorders. Increasingly, the arthritides have shown statistically quantifiable rhythmic parameters. Included in the latter group are joint pain and joint size. In addition, a number of drugs used to treat rheumatic diseases have varying therapeutic and toxic effects based on the time of day of administration. Among these drug classes are nonsteroidal antiinflammatory drugs, glucocorticoids, and a number of cytostatic agents. In the last group of agents, experience in treating malignant disease suggests that time-specified treatment may reduce the toxic effects of low-dose cytostatic treatment of rheumatoid arthritis (RA) and related diseases. This article reviews that evidence and suggests a rationale for the timed treatment of RA with methotrexate. | |
| 7741497 | Methotrexate in the treatment of psoriasis at the National Skin Centre, Singapore. | 1994 Nov | In the last 30 years, methotrexate has been used for treating psoriasis, rheumatoid arthritis and other inflammatory disorders. Much has been learned about its beneficial and adverse effects. Long-term use produces different effects from short-term use. This study was undertaken to study the long-term use of methotrexate in our local population. It is a retrospective study where the case reports of 72 psoriatic patients on methotrexate were analysed for its use, side effects, the monitoring of side effects and its efficacy. Our study showed that methotrexate was effective in 61 (86.0%) patients, had some side effects in 10 (14.2%) patients and was relatively safe. It also helped psoriatic arthropathy. However, adequate and close monitoring is required to prevent liver fibrosis and cirrhosis. | |
| 19077981 | Effects of Second-line Drugs on the Progression or Regression of Rheumatoid Nodules. | 1995 Aug | Second-line drugs may have different effects on nodules than on synovitis. In this study, we have begun to evaluate the effects of these agents on rheumatoid nodules. The appearance, progression, or regression of rheumatoid nodules were studied in an open series of 119 patients with rheumatoid arthritis (RA) seen at an academic center over the last 20 years. Fifty-six of these patients had nodules during a mean period of observation of 5.4 years. During this time, 1-5 second-line drugs were taken. Our population had a higher prevalence of nodules (47%) than did patients in most previously reported series. New nodule formation and nodule progression were most often associated with methotrexate (n = 21, 68%) but were also noted during use of gold salts (n = 6, 18%) and hydroxychloroquine (n = 3, 8%). Nodule regression and even complete resolution of nodules was most often observed with hydroxycholoroquine (n = 14, 36%) and with sulfasazine (n = 6, 32%) and injectable gold (n = 5, 14%). Changes in nodules occurred without consistent relation to synovitis. Second-line drugs that may modify the articular aspects of RA may exert varying effects on nodules. These very different effects, if confirmed, suggest important differences in drug mechanisms of action on this basic manifestation of RA. | |
| 8761799 | [Use of methotrexate in spondylarthropathies. Review of the literature]. | 1996 | Methotrexate (MTX) is one of the most effective treatments of rheumatoid arthritis. It has also been used in other conditions such as spondylarthropathies (SPA). The literature concerning MTX in SPA was reviewed. Thus, MTX has been mainly prescribed in psoriatic arthritis and Reiter's syndrome with success for dermatological manifestations of these diseases. However, only a few controlled trials have been conducted in psoriatic arthritis and only one placebo controlled study did not demonstrate a real beneficial effect. Furthermore, it seems that MTX has no influence on the radiological outcome of psoriatic arthritis. There has been no controlled study upon the efficacy of MTX in Reiter's syndrome, ankylosing spondylitis or arthropathy associated with inflammatory bowel diseases. Such studies in SPA are required to evaluate the responding conditions, the efficacy, the side-effects, and the effective dose of MTX. |