Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3260783 | The effects of leucovorin (folinic acid) on methotrexate therapy in rheumatoid arthritis p | 1988 Jul | High-dose leucovorin (folinic acid) supplementation was tested in a prospective, unblinded manner for 4 weeks in 7 rheumatoid arthritis patients who were being treated successfully with low-dose methotrexate (MTX). Nausea caused by MTX disappeared; however, the underlying rheumatic disease worsened in all patients. Subjective clinical assessment, Ritchie articular index, grip strength, erythrocyte sedimentation rate, and levels of C-reactive protein showed statistically significant deterioration. All these parameters improved after the leucovorin was stopped. This is the first direct clinical evidence implying folate antagonism in the action of low-dose MTX therapy in rheumatoid arthritis patients. | |
| 1927044 | [Immunogenetic prognosis of the effectiveness of cytostatic therapy of rheumatoid arthriti | 1991 | The time course of in vitro cellular immune reactions by using cyclophosphane, prospidin , and methotrexate was examined in 39 patients with rheumatoid arthritis to make predictions of the efficacy of its cytostatic therapy. The agents were evaluated for effects on the expression of Ia-like antigens on the peripheral lymphocytes and synovial fluid of the patients. The optimal doses of the agents for this testing had been chosen in the lymphoid cells from MRL31 lpr mice. The active dosage forms of the cytostatics for the experiment were obtained by administering native agents into the retrobulbar plexus of Balb/c mice, followed by blood isolation of active metabolites . The Ia-like antigen pre-expression index which is the ratio of the proportion of Ia-positive lymphocytes in control cultures to that of the cells in the culture after drug addition was used as a marker of the baseline cellular immunity in the patients. The patients having the index more than 1.5 were considered to be sensitive, those with less than 1.5 were insensitive to the drug. Thus, the Ia-like antigen pre-expression index may be used as a predictor in the assessment of the expediency of prospidine use. | |
| 2405864 | The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patie | 1990 Jan | Thirty-two patients with rheumatoid arthritis completed a 24-week, placebo-controlled, double-blind trial of folic acid (FA) supplementation during low-dose methotrexate (MTX) therapy. Administration of the daily FA supplement significantly lowered toxicity scores without affecting efficacy, as measured by joint counts, joint indices, and patient and physician evaluation of disease activity. Fifteen patients experienced some sort of toxicity; 67% were in the placebo group, and 33% were in the FA supplement group. Four patients in the placebo group had toxicity levels serious enough to require discontinuation of the MTX, while no patients in the FA supplement group discontinued MTX because of toxicity. Low-normal initial plasma and red blood cell folate levels were predictive of future toxicity with MTX therapy. We conclude that a daily supplement of 1 mg of FA during low-dose MTX therapy (median dose 7.5 mg/week [16.4 mumoles]) is usefull in lessening toxicity without altering efficacy during the first 6 months of treatment. | |
| 3319362 | Current concepts in clinical therapeutics: disease-modifying drugs for rheumatoid arthriti | 1987 Jun | The epidemiology, pathophysiology, clinical features, diagnosis, and clinical course of rheumatoid arthritis (RA) and the role of disease-modifying antirheumatic drugs (DMARDs) in its treatment are reviewed. RA, a widespread disease affecting people of all races and sexes around the world, has an unknown and perhaps multifactorial etiology. Conflicting evidence supports an immune-complex, infectious, metabolic, or genetic basis for RA. The disease affects diarthrodial joints and begins as an immune response to unknown antigenic stimuli. A proliferative process ensues, leading to formation of a vascular lesion called a pannus, which then infiltrates into cartilage, subchrondral bone, and tendon. This destructive phase leads to classic RA symptoms of pain, limitation of motion, swelling, heat, and redness of the affected joint. Symptoms and laboratory tests form the basis for diagnosis. For most RA patients, conservative therapy provides substantial benefit. In those patients who suffer from unrelenting and progressively destructive disease, more aggressive intervention is necessary to prevent permanent disability. The DMARDs are reserved for treatment of this group of patients. DMARDs include such diverse agents as the gold compounds aurothioglucose, auranofin, and gold sodium thiomalate; the antimalarials hydroxychloroquine sulfate and chloroquine phosphate; penicillamine; and the cytotoxic agents azathioprine, methotrexate, and cyclophosphamide. DMARDs are effective but toxic therapeutic agents. Because of the toxicities of these agents, careful monitoring at regular intervals is necessary throughout the duration of therapy. For patients in whom these drugs demonstrate efficacy and are tolerated, the DMARDs may attenuate the disabling effects of long-term erosive disease. | |
| 3258915 | High dose intravenous methotrexate with leucovorin rescue in rheumatoid arthritis. | 1988 Feb | Five patients with severe, treatment refractory rheumatoid arthritis were treated with high dose intravenous methotrexate (500 mg/m2) followed by leucovorin (50 mg/m2). Four courses of chemotherapy were given over a 2-month interval. At the end of the final course, there was a 50% or greater improvement in joint swelling and pain indices and morning stiffness in all patients. Clinical responses persisted for 6-14 weeks posttherapy. High dose methotrexate-leucovorin was associated with a significant reduction in DR antigen expression on peripheral Leu 2, Leu 3 and Leu 4 lymphocytes. | |
| 2674426 | Methotrexate pharmacokinetics in patients with rheumatoid arthritis. | 1989 Jun | Few studies have evaluated the pharmacokinetics of low dose oral methotrexate (MTX) therapy. MTX pharmacokinetics were studied in 10 patients with classic rheumatoid arthritis (RA) after a single 7.5 mg oral dose. MTX was rapidly absorbed. Peak concentrations varied considerably, ranging from 0.31-0.72 microM. Measurable drug concentration was found in all patients at 24 h after the dose. CL/F-MTX = 145 +/- 52 ml/min/1.73 m2 and elimination half-life was 4.5 +/- 0.89 h. Oral MTX given as a single weekly dose has predictable pharmacokinetics. Further studies to examine what relationship exists, if any, with efficacy and toxicity of MTX in RA must be undertaken. | |
| 2257452 | The cycling of combination antirheumatic drug therapy in rheumatoid arthritis. | 1990 Dec | In this open pilot study a combination of hydroxychloroquine, prednisolone and alternating months of treatment with sulphasalazine or oral weekly pulse methotrexate has been investigated in 16 patients with rheumatoid arthritis (RA) refractory to a total of 67 disease suppressive medications. Results at 3 months indicated significant improvements in visual analogue score for pain, joint count, Ritchie index, scale of disability related to activities of daily living, ESR, rheumatoid factor and C-reactive protein. This degree of improvement, however, was not maintained 6 and 12 months after commencement of treatment. Pain score, Ritchie index and ESR were the only parameters demonstrating significant improvement at 12 months. Therapy was terminated in eight patients, half due to lack of efficacy and half because of side effects. | |
| 1749945 | A double-blind comparison of parenteral methotrexate and parenteral gold in the treatment | 1991 Oct | One hundred two patients with active erosive rheumatoid arthritis (RA) without malalignment or deformities (median disease duration, 14 months) entered a double-blind, randomized study to compare the effects of 50 mg gold sodium thiomalate (GST) with 15 mg methotrexate (MTX) administered intramuscularly for 12 months. Roentgenograms of hands, wrists, and forefeet were taken at baseline and after 6 and 12 months, and 32 joints were evaluated according to Larsen. Sixteen of 50 patients in the MTX group were withdrawn; one patient in the MTX group died of cerebral bleeding that was not related to treatment. Thirty-four GST patients and 44 MTX patients were evaluated for efficacy. Thirty-eight joints were counted. The number oftender and swollen joints, the Lansbury articular index, morning stiffness, activities of daily living (ADL) score, and erythrocyte sedimentation rate improved significantly in both groups without statistical intergroup differences. After 12 months, there was a significant deterioration of the mean Larsen index and the number of joints with erosions without intergroup difference. However, the radiological progression was retarded significantly during the second 6-month period in the gold group, whereas this effect was less pronounced in the MTX group. At 12 months, the progression rate was the same in both groups. | |
| 2251507 | Proposition: methotrexate should not be the first second-line agent to be used in rheumato | 1990 Oct | Although methotrexate (MTX) is an effective antirheumatic drug, it cannot clearly be defined as a disease modifying antirheumatic drug (DMARD), when this term is characterized by its effect on radiographs or laboratory data. Current data, in the form of small studies or case reports, show that MTX's hepatic toxicity is not yet fully defined, that its acute pulmonary toxicity is significant, that systemic fungal infections may be associated with MTX use in rheumatoid arthritis (RA), that unexplained significant weight loss can be a problem, and that the consequence of drug interactions with MTX are not yet fully known. Thus, although clearly an effective antiinflammatory drug in RA, the place of MTX in the RA armamentarium is not fully defined. For this reason, MTX should not at present be used as the first second-line agent in RA after nonsteroidal antiinflammatory drugs (NSAIDs) fail. | |
| 1930313 | Retardation of radiologic progression in rheumatoid arthritis with methotrexate therapy. A | 1991 Oct | We evaluated the effects of methotrexate (MTX) on radiographic changes of rheumatoid arthritis (RA) in the hands, wrists, and feet of 31 patients who completed at least 24 months of treatment. Radiographs were obtained at baseline and every 1 or 2 years thereafter. MTX was administered for 2-6 years (mean 3.9 years); the total dose was 1,925 mg (range 970-3,810 mg). The mean duration of disease at baseline was 8.1 years (range 1-26 years). Radiographs taken over 1-5 years during previous, clinically ineffective, gold therapy (mean 2.2 years) were available for 24 patients, and the changes over time were compared. During MTX treatment, the mean number of swollen joints decreased from 22.5 to 8.3 (40 joints evaluated), and the mean erythrocyte sedimentation rate decreased from 61.6 mm/hour to 28.4 mm/hour. Thirty-six (19%) of 190 joints with Larsen scores of 0 at baseline progressed to a score of 1 or 2 within 1 year of beginning MTX, whereas with gold, 37 (44%) of 89 joints progressed (P less than 0.001). Of 419 joints with Larsen scores of 1, 12.5% deteriorated within 1 year with MTX treatment, compared with 14.7% of 183 joints during gold therapy (P not significant). There were no between-treatment differences for joints with higher Larsen scores. During gold therapy, the mean Larsen index (score per joint) for the hand and wrist joints (18 joints counted) progressed from 1.45 to 1.82 over a mean of 22.1 months, and during MTX, from 1.82 to 1.97 over a mean of 48.0 months.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3263759 | Variability of methotrexate pharmacokinetics and pharmacodynamics. | 1988 | It is apparent that MTX is a useful agent in the treatment of rheumatoid arthritis resistant to first and second line therapies. However, despite its long term use in this disease, considerable uncertainty exists about the basic pharmacokinetics of low dose oral MTX and therefore about its pharmacodynamics. It is probable that when MTX is re-examined with the help of modern analytical technology in a rheumatoid setting that pharmacological insights to the variability in dose-response relationships for efficacy and certain toxicities may emerge. There is still considerable uncertainty of the hepatotoxic potential of MTX. Further investigation of the accumulation of active polyglutamated MTX in liver may throw light on the likelihood of promoting iatrogen disease and perhaps the contribution of oral administration to this problem. Finally, examination of dose-response relationship utilising accurate pharmacokinetics may help to establish guidelines for the safe and effective usage of MTX in rheumatoid arthritis. | |
| 3422015 | Accelerated nodulosis and vasculitis during methotrexate therapy for rheumatoid arthritis. | 1988 Sep | Three women with classic rheumatoid arthritis, who were receiving weekly doses of methotrexate (MTX), developed accelerated subcutaneous nodulosis, despite good response to the drug. In 2 of the patients, the onset of nodulosis occurred within 3 months and 5 months, respectively, after starting MTX; in the third patient, it was observed only after 4 years of MTX therapy. In all 3 patients, the onset was unusually abrupt, with extensive distribution and remarkable nodule size. Additional manifestations of cutaneous vasculitis in 2 of the patients and Raynaud's phenomenon in the third appeared concomitantly with the nodulosis. Physicians prescribing MTX therapy for patients with rheumatoid arthritis should be aware of these potential complications. | |
| 3064524 | Immunosuppressive therapy in rheumatoid arthritis. | 1988 | Immunosuppressive drugs are used since 1951 for the treatment of rheumatoid arthritis. The most extensive used ones are azathioprine, cyclophosphamide, chlorambucil and methotrexate. The efficacy of these immunosuppressive drugs is clinical proven. Nevertheless it is necessary to use these drugs in severe disease only that has failed to respond to less toxic agents. The number of severe side effects is higher and the consequences of this therapy concerning cancerogenity is not clear yet. The efficacy and side effects of these drugs are discussed and guidelines for using immunosuppressive drugs in the treatment of rheumatoid arthritis are given. | |
| 2363742 | Biliary elimination of low-dose methotrexate in humans. | 1990 Jun | We studied the pharmacokinetics of methotrexate (MTX) in a 64-year-old man with rheumatoid arthritis. After 6 months of treatment, acute clinical complications arose, requiring emergency laparotomy and cholecystotomy. A biliary tube was inserted, and this allowed for direct analysis of the bile. The pharmacokinetics of 2 separate doses of MTX (orally and intravenously) were assessed (dosage 10 mg/m2). No substantive differences in the pharmacokinetics were found between pre- and post-cholecystotomy MTX treatment, including clearance rates, volumes of distribution, and terminal half-lives. The results, however, demonstrated a change in the bioavailability of the drug (decreasing from 84.7% to 38.9%). Based on extrapolations of the data, with assumed rates of bile flow, the findings also suggest that there is substantial biliary elimination of MTX (8.7-26.0%) and its principal 7-hydroxy metabolite (1.5-4.6%). | |
| 2724250 | Increasing methotrexate effect with increasing dose in the treatment of resistant rheumato | 1989 Mar | Forty-six patients with recalcitrant rheumatoid arthritis entered a trial encompassing a 2-week inpatient period plus a 16-week, randomized double blind, parallel study comparing placebo, 5 mg/m2 and 10 mg/m2 oral weekly methotrexate (MTX). An additional 6 patients, given 20 mg/m2 MTX, contributed to the toxicity, but not the efficacy analysis. All patients had "failed" either gold or D-penicillamine. A linear dose response relationship (placebo vs 5 mg/m2 vs 10 mg/m2) was found for 5 of 11 outcome variables: patient pain and patient global scale, physician global scale, joint tenderness count and activity of daily living scale (p less than 0.05 for each). Gastrointestinal toxicity (p = 0.002), dyspepsia (p less than 0.03) and stomatitis (p less than 0.09) occurred more commonly with MTX, and a general trend, although not significant, was found toward a dose toxicity relationship. | |
| 3139877 | A randomized controlled trial of parenteral methotrexate compared with sodium aurothiomala | 1988 | Forty patients with rheumatoid arthritis (RA) were enrolled in a double blind study of 26 weeks duration designed to compare the efficacy and safety of parenteral methotrexate and sodium aurothiomalate (GSTM) in the treatment of RA. All the patients had active RA and none had previously received gold, D-penicillamine or immunosuppressive therapy. Patients were randomized to receive weekly intramuscular (IM) injections of either methotrexate 10 mg or GSTM 50 mg. Two patients taking methotrexate and 7 taking GSTM were withdrawn before 26 weeks. Methotrexate was as effective as GSTM as measured by numbers of swollen or tender joints, morning stiffness, grip strength, pain scale and erythrocyte sedimentation rate. Five patients taking methotrexate and 11 taking GSTM presented side effects (p = 0.05). Total number of adverse reactions was 5 for the methotrexate group and 15 for the GSTM group (p less than 0.01). Our data suggest that low dose IM methotrexate is less toxic and as effective as GSTM for the treatment of RA during the first 6 months of therapy. | |
| 1757932 | Treatment of rheumatoid arthritis with methotrexate: a prospective open longterm study of | 1991 Sep | One hundred and ninety-one patients with severe rheumatoid arthritis (RA) were included in a prospective open longterm study of the safety, efficacy and maintenance of methotrexate (MTX) treatment. The mean duration of MTX treatment was 19 +/- 13.2 (3-58) months; the mean weekly dose of MTX was 10.2 +/- 0.2 mg. Analysis of the 191 patients in an intent-to-treat manner showed a significant improvement of all the clinical variables and a decrease of erythrocyte sedimentation rate with a steroid sparing effect. The probability of continuing MTX therapy for up to 2 years was 65% and for up to 5 years was 46%. Adverse effects of MTX occurred in 37.1% of the patients, but only 15.7% discontinued MTX permanently. | |
| 1941837 | Low dose methotrexate therapy for rheumatoid arthritis complicated by pancytopenia and Pne | 1991 Aug | In a patient with rheumatoid arthritis pancytopenia and Pneumocystis carinii pneumonia occurred during low dose methotrexate therapy. This case emphasizes the potential development of opportunistic infections even with low dose methotrexate. Pneumocystis carinii pneumonia resembles methotrexate induced pneumonitis. Therefore opportunistic infections should be considered before a definite diagnosis of methotrexate induced pneumonitis is made. | |
| 3548733 | Lack of association between HLA-DR2 and clinical response to methotrexate in patients with | 1987 Feb | Recent studies have indicated an association between the HLA-DR2 phenotype and substantial response to methrotrexate in patients with rheumatoid arthritis (RA). To further resolve this issue, we analyzed this relationship. Our data, obtained from a multicenter, double-blind study of rigorously assessed patients with RA, demonstrated that neither HLA-DR2 nor any other HLA-DR specificity is significantly associated with a substantial clinical response to methotrexate in patients with RA. | |
| 3718554 | Impact of specific therapy upon rheumatoid arthritis. | 1986 May | We performed a prospective, parallel, descriptive study of 737 consecutive new uses for 11 drugs prescribed for patients with definite or classic rheumatoid arthritis. The patients were from 5 geographically dispersed sites. Researchers used validated outcome assessment instruments to measure endpoints of disability, pain, patient global assessment, medication costs, laboratory costs, and number of physician visits. Patients were studied by strict prospective protocol at 6-month intervals for 3 years. Controls included parallel results with other drugs, and before and after values for the individual patient. Beneficial effects were observed with the "disease-modifying" drugs: intramuscular gold, penicillamine, and methotrexate. Of these, gold had the most apparent effect. An average of 9 months of gold therapy resulted in highly significant reductions in disability (P less than 0.005), pain (P less than 0.001), and patient global assessment (P less than 0.005). However, patients receiving gold and methotrexate had nearly twice as many visits to physicians. In addition, drug costs increased strikingly with gold, and laboratory costs tripled. Relatively minor differences among nonsteroidal antiinflammatory agents were difficult to interpret. The outcome assessment techniques used in the study are sensitive measures, which confirm the results of experimental studies and extend observations to new outcomes, including cost and disability. |