Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3978894 | Measurements of red blood cell methotrexate concentrations and lymphocyte subsets during t | 1985 Jan | Nine patients with rheumatoid arthritis were treated with low dose oral weekly methotrexate for 6 months. Successful therapy was not associated with changes in concentrations of total circulating lymphocytes nor with alterations of T lymphocytes in the helper-inducer, OKT4, or cytotoxic-suppressor, OKT8, subpopulations. Concentrations of methotrexate in circulating erythrocytes stabilized by 1 month of therapy and this measurement did not correlate with clinical efficacy or methotrexate toxicity in the long-term patient assessments. | |
| 3891280 | The use of methotrexate in rheumatoid arthritis. | 1985 May | The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5-15 mg/wk in a "pulse" fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded. | |
| 4064588 | C-reactive protein levels in patients with rheumatoid arthritis: the impact of therapy. | 1985 Sep | C-reactive protein levels were measured in sera of 111 patients with rheumatoid arthritis and were compared with erythrocyte sedimentation rate. The patients were divided into six groups according to drug therapy. Comparison between the groups suggests that CRP correlates best with ESR in patients treated with penicillamine and in patients in clinical remission. Patients treated with gold, NSAID or methotrexate have a weaker correlation between the two parameters, while steroid therapy yields the poorest correlation which is not statistically significant. Our data suggest that although CRP is a sensitive index of disease activity, the specific drug taken by the patient must be considered before interpreting the results. | |
| 4037555 | Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a r | 1985 Oct | Twelve patients with refractory rheumatoid arthritis were treated with weekly pulse methotrexate in a double-blind, placebo-controlled, crossover study. After 13 weeks of therapy, patients receiving methotrexate showed greater improvement, judged by degree of joint swelling and tenderness, duration of morning stiffness, and subjective assessments of clinical condition, compared to those receiving placebo (p less than or equal to 0.002). This improvement was associated with a decrease in sedimentation rate and decreases in levels of IgG, IgM, and IgA; no changes were seen in serum rheumatoid factor titer or complement protein levels. Proportions of mononuclear cell subsets that were abnormal before treatment (decreased percentage of total T cells, increased percentage of monocytes) improved toward normal after therapy with methotrexate. However, no changes were seen in elevated pretreatment Leu-3/Leu-2 ratios, in in-vitro proliferative responses of lymphocytes to mitogens, or in immunoglobulin secretory responses to pokeweed mitogen. Weekly pulse methotrexate is effective in the short-term treatment of refractory rheumatoid arthritis. Little evidence for cellular immune suppression was associated with this clinical benefit. | |
| 4062454 | Pneumonitis complicating low-dose methotrexate therapy in rheumatoid arthritis. | 1985 Nov | Three of 95 patients with rheumatoid arthritis who were being treated with low-dose (5 to 15 mg/wk) methotrexate sodium developed the clinical, radiographic, and pathologic features of methotrexate-associated pulmonary injury. Marked hypoxemia emphasized the severity of illness in our patients; lowest oxygen pressure values for each patient were 35 mm Hg, 42 mm Hg, and 45 mm Hg. The management of our patients with a pulmonary toxic reaction to methotrexate included discontinuing the drug treatment, antibiotic therapy until an infectious cause was excluded, and high-dose methylprednisolone. Two patients recovered and one died. Contrary to an earlier report that suggested that pneumonitis occurred only with methotrexate sodium doses exceeding 15 mg/wk, our three cases demonstrate that a severe pulmonary toxic reaction may also complicate low-dose weekly methotrexate therapy of rheumatoid arthritis. | |
| 7161777 | Low dose methotrexate in rheumatoid arthritis. | 1982 Nov | A systematic analysis of the efficacy of methotrexate (MTX) in severe rheumatoid arthritis (RA) was carried out. Twenty-one patients with severe classical RA resistant to conventional therapy were treated with 7.5 to 25 mg of oral or intramuscular MTX for 3-114 weeks (mean of 38 weeks). Eleven patients (52.4%) showed definite clinical improvement and a fall in sedimentation rate; some improvement was seen in 5 other patients (23.8%). Two patients were unresponsive. Three patients discontinued MTX, 1 because of acute hepatitis and the other 2 because of noncompliance and fear of toxicity. Abnormal liver function tests reversible with modification of therapy occurred frequently. Other side effects were minor. The results of this uncontrolled study indicate that MTX may be an effective drug for the treatment of severe RA. Double blind trials and longterm followup are needed prior to its widespread use in RA. | |
| 3913774 | Historical perspective on the use of methotrexate for the treatment of rheumatoid arthriti | 1985 Dec | Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis. By 1972, low dose pulse methotrexate was observed to be useful in RA, but it was not until 1980 that additional beneficial effects of methotrexate in the treatment of patients with refractory RA appeared in the literature. Subsequently, both uncontrolled experience and double blind prospective trials have demonstrated efficacy and acceptable tolerability and safety of methotrexate in the treatment of patients with RA. Guidelines for its use in patients with RA still need to be developed. | |
| 6681135 | Methotrexate levels, a guide to therapy? | 1983 Apr | Methotrexate (MTX) is being used with increasing frequency in the treatment of inflammatory arthritis. Seventy-one patients have been treated with MTX with only five ceasing treatment because of toxicity. From a study of the serum levels of this drug, we believe that 10 mg intramuscularly once per week should be an optimum method of treating arthritis. The measurement of a 24 hour serum level of MTX, which normally is less than 0.01 mumole/litre after 10 mg I.M., should aid in identifying those patients more at risk of developing toxicity. | |
| 3883172 | Efficacy of low-dose methotrexate in rheumatoid arthritis. | 1985 Mar 28 | Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug. | |
| 7420331 | Low dose pulse methotrexate therapy in rheumatoid arthritis. | 1980 Jul | Thirty-two patients with definite or classical rheumatoid arthritis were treated with low dose pulse methotrexate (MTX). A therapeutic response was shown in 2/3 of the patients by statistically significant joint changes and improved global response. Greater than one-half of those who improved demonstrated a drop in sedimentation rate. Eight patients discontinued treatment because of inefficacy and 2 because of gastrointestinal distress. One patient died of neoplasm. Five liver biopsies performed in patients with abnormal liver enzymes demonstrated no MTX related changes. We conclude that MTX may be an effective alternative to other more toxic immunosuppressive regimens and should undergo future evaluation. | |
| 6660241 | Methotrexate therapy in rheumatoid arthritis: 15 years experience. | 1983 Dec 30 | An increasing amount of clinical data indicates that low-dose methotrexate therapy for rheumatoid arthritis is both effective and free of serious side effects. Since 1967 we treated 78 patients with definite or classic rheumatoid arthritis who showed inadequate response to conventional therapy. Up to 15 mg of methotrexate was given weekly by the intramuscular route. Morning stiffness, severity of pain at rest and with activity, extent of active synovitis, functional capacity, change in steroid dosage, complete blood count, erythrocyte sedimentation rate, and gamma glutamyl transpeptidase were monitored. Overall assessment indicated that 45 of the 78 (58 percent) patients showed marked improvement or complete remission, usually within four weeks. When maximum improvement was obtained, most patients were switched to oral therapy with a variable degree of success, and dosage was decreased as tolerated. No serious toxicity was noted. In 34 patients a total of 67 liver biopsy specimens were obtained, some after as long as 15 years of therapy. Minor changes observed are the same as in patients with rheumatoid arthritis not treated with methotrexate. Because the risks did not appear justified, routine annual biopsies were discontinued. In contrast to other cytotoxic drugs, no carcinogenesis has been demonstrated with methotrexate. It appears that methotrexate is approximately as effective as intramuscular gold and D-penicillamine but that it has a quicker onset of response and less serious toxicity. | |
| 6394758 | A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid | 1984 Dec | Forty-eight patients with rheumatoid arthritis refractory to other treatments were studied in a placebo controlled trial of methotrexate (MTX) in 2 institutions. Once weekly for 6 weeks, the patients were injected with placebo (Group 1), MTX 10 mg (Group 2), or MTX 25 mg (Group 3). Then, for the next 6 weeks, Group 1 received MTX, either 10 or 25 mg/wk, and Groups 2 and 3 continued their same dose. Adverse reactions necessitated change from 25 mg to 10 mg in some patients, but no major side effects of MTX were noted. At 6 weeks, the effect of the 2 MTX doses did not differ significantly but patients on MTX had fared significantly better (p less than 0.005 - less than 0.001) than those given placebo. At 12 weeks, all indices showed significant improvement in Group 1 and maintenance or enhancement of the improvement in Groups 2 and 3. We conclude that weekly low dose MTX therapy is efficacious for refractory rheumatoid arthritis. | |
| 4036984 | Low-dose methotrexate treatment of rheumatoid arthritis. Long-term observations. | 1985 Sep | Of 21 patients with rheumatoid arthritis who began to receive low-dose weekly methotrexate up to five years ago, 15 (71 percent) have continued to take this drug for a mean of 42 months and have received a mean total dose of 2,021 mg (range: 915 to 3,075). The clinical improvement noted at the first follow-up (11 months) was sustained throughout this follow-up period (42 months). Three patients (14 percent) have had complete clinical remission and nine others (43 percent) have had an excellent response. Methotrexate was discontinued in four patients between the first and second follow-up because of planned pregnancy (one), gastrointestinal toxicity (two), and fear of toxicity (one). Liver toxicity assessed in these 21 patients and four others receiving long-term methotrexate therapy revealed acute hepatitis in one and elevated transaminase levels in 12 (48 percent). Liver biopsy specimens in 17 patients after a mean of 1,950 mg of methotrexate (range: 915 to 3,125) revealed mild fibrosis in six and no cirrhosis. Methotrexate can continue to suppress rheumatoid synovitis over a prolonged period of time with minimal toxicity in most patients. Hepatic fibrosis and cirrhosis due to methotrexate may be less common in rheumatoid arthritis than has been reported in psoriasis. | |
| 3893441 | Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid | 1985 Jul | One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity. | |
| 6442225 | The activity of natural killer cells in patients with rheumatoid arthritis: I. The effect | 1984 Jul | The role of natural killer (NK) cells in vivo remains uncertain, but they have been implicated in a number of protective and aggressive host responses. We have found the NK activity of most patients with rheumatoid arthritis (RA) to be significantly depressed below the values for a control healthy population. This depression is not related to the use of myochrysine, methotrexate or penicillamine. Auranofin, which has a stimulatory effect in vitro, seemed in vivo to cause a further depression. ASA and indomethacin, when given to normal subjects, stimulated NK activity. The reduced NK activities seen in patients with RA taking these and other non-steroidal anti-inflammatory agents remains unexplained. | |
| 356763 | Intra-articular methotrexate. Clinical and laboratory study in rheumatoid and psoriatic ar | 1978 Aug | The effects of intra-articular methotrexate (MTX) were compared with saline in 20 patients with persistent knee effusions due to rheumatoid arthritis (15) and psoriasis (5) in a double-blind pilot study. Clinical improvement was seen in most patients given either MTX or saline and was attributed to joint irrigation during arthroscopy and the placebo effects. MTX had a local anti-inflammatory effect in the psoriatic arthropathies; the percentages of polymorphonuclear cells and pyroninophilic mononuclear cells in synovial fluids fell sharply. Intraarticular hydrocortisone acetate was not anti-inflammatory in 2 psoriatic patients treated subsequently. The anti-inflammatory action of MTX in joints may resemble its effectiveness in controlling the rash of psoriasis. | |
| 3970039 | Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatmen | 1985 Jan 21 | Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications. | |
| 3913772 | Short term efficacy of methotrexate in the treatment of rheumatoid arthritis. | 1985 Dec | Methotrexate is easily administered, widely accepted by patients, and has a rapid therapeutic effect. With careful attention to known risk factors, such as alcoholism, diabetes, obesity, and renal disease, it is a useful agent for the treatment of refractory rheumatoid arthritis (RA). Although rheumatologists have been using methotrexate in the treatment of RA for some time, controlled studies have been needed to establish the safety and efficacy of this agent. This paper will review the findings of the Cooperating Clinics of the American Rheumatism Association, as well as other studies that have investigated the short term efficacy of methotrexate. | |
| 6697645 | Low-dose methotrexate kinetics in arthritis. | 1984 Mar | Twelve patients with either rheumatoid or psoriatic arthritis were injected with a 10-mg bolus dose of methotrexate (MTX) either intramuscularly (n = 6) or intravenously (n = 6) and the MTX concentration in their sera was determined by radioimmunoassay. MTX concentration--time data fitted triexponential equations. Doses injected intramuscularly were rapidly and completely absorbed. There were no significant intergroup differences in drug mean t 1/2, volume of distribution, and total body clearance. In nine patients serum MTX concentrations remained above the suggested critical level of 0.01 mumol throughout the 24-hr study irrespective of the route of administration, but MTX did not cumulate in the serum. We conclude that the behavior of low doses of MTX in patients with arthritis closely resembles the pattern in patients receiving intermediate and high doses for the treatment of neoplasia. | |
| 3913773 | Longterm methotrexate therapy in rheumatoid arthritis: a review. | 1985 Dec | A review of the literature on the longterm use of methotrexate in patients with rheumatoid arthritis (RA) showed that many questions on protocol remain unanswered. Although rheumatologists have adopted certain guidelines previously followed by dermatologists for psoriasis patients, rheumatology literature offers no set of rules for using the drug in treating patients with RA. The use of liver function tests and liver biopsy specimens to predict and assess hepatotoxicity associated with methotrexate use is also discussed. |