Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2724249 | Methotrexate therapy in rheumatoid arthritis: 2-year retrospective followup study. | 1989 Mar | Clinical and laboratory data in 124 patients with rheumatoid arthritis treated with methotrexate (MTX) were retrospectively reviewed over the initial 2 years after the start of treatment. Clinical improvement occurred in 103 (83%) patients after 12 weeks of treatment. At 2 years of followup, 60 patients (48%) continued to receive MTX with sustained clinical benefit. It has been discontinued in 64 (52%) patients (adverse drug reactions in 38, lack of clinical benefit in 15, and miscellaneous reasons in 11). Patients with adverse drug reactions had higher initial serum creatinine and blood urea nitrogen values than patients without adverse drug reactions. | |
| 1921820 | Neutropenia due to low-dose methotrexate therapy for psoriasis and rheumatoid arthritis ma | 1991 Oct 7 | OBJECTIVE: To review experience with neutropenia related to low-dose methotrexate therapy in patients with psoriasis and rheumatoid arthritis. DESIGN: Retrospective review of medical records. SETTING: A 509-bed Melbourne teaching hospital. PATIENTS: Five patients admitted in 1987 and 1988, with neutrophil counts of less than 1 x 10(9)/L, given low doses of methotrexate for psoriasis or rheumatoid arthritis. MAIN OUTCOME MEASURES: Death, or length of hospital admission. FINDINGS: Four patients were women, and one a man; three had been treated for psoriasis, and two for rheumatoid arthritis. Ages ranged from 56 to 91 years. The eldest patients, aged 77, 81 and 91 years, died. The other two were discharged after 43 and 48 days. Prior to or shortly after admission, four patients were treated with penicillin antibiotics which may have interfered with methotrexate excretion. CONCLUSIONS: Methotrexate clearances (related to creatinine clearance rates and presumably low) were probably reduced sufficiently by concomitant therapy to result in neutropenia. Practitioners using methotrexate should be aware of drug interactions resulting in delayed methotrexate excretion. Blood counts should be monitored after changes in therapy, especially in patients with impaired renal function, such as the elderly. | |
| 3823910 | Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotr | 1987 Feb | Methotrexate therapy has been effective in the treatment of RA with short term experience suggesting little serious adverse reactions. Our review of 168 patients receiving methotrexate has identified nine patients with probable or possible methotrexate-induced pulmonary toxicity, giving a prevalence of 5% and an incidence of 3.9 per 100 patients per year. No clinical or laboratory features showed an association that could potentially predict the development of pulmonary disease. All patients experienced complete recovery with supportive care and/or corticosteroid therapy. Clinical monitoring for this complication is warranted in all patients receiving long term methotrexate therapy for RA. | |
| 3548154 | [Treatment with low-dose methotrexate in chronic polyarthritis. Review of the literature]. | 1986 Nov | The therapeutic effect of low-dose MTX-treatment (10-25 mg/week) in active rheumatoid arthritis can be demonstrated by an improvement in clinical and laboratory parameters of disease activity already after 4-6 weeks. The mode of action is not fully understood. Direct anti-inflammatory effects seem to be more important than the weak immunosuppressive properties. Methotrexate treatment is indicated in all very active cases of rheumatoid arthritis, which do not respond to, or do not tolerate, conventional slow-acting antirheumatic drugs. In severe, rapidly progressing diseases MTX can be given without waiting for the effect of other disease modifying drugs. MTX is administered once a week i.v., i.m. or in one oral dose before breakfast. Absorption is reduced by food. The initial weekly dose is 15-25 mg and can be reduced to a minimum of 10 mg (7.5 mg) according to the clinical effect. A combination with antimalarials or gold salts is possible. The prescription of MTX is contraindicated in cases of renal function disturbances, active liver disease, bone marrow disturbances, active infectious diseases, pregnancy and excessive alcohol consumption. The most common side-effects are nausea and vomiting, stomatitis, transient elevations of transaminases. Rare conditions are leucopenia, thrombocytopenia and lung infiltrations. The side-effects are dose-related and disappear with dose reduction. They can be avoided by administering leucovorin 12 hours after giving MTX. Before starting the treatment total blood count with differential count and platelet count, serum creatinine and liver enzymes should be done. These laboratory studies have to be repeated every week for the first month, every two weeks up to the third month and every 1-2 months thereafter. When contraindications are considered and regular controls are made methotrexate is better tolerated than other cytotoxic agents. The rate of withdrawals is lower than with gold-treatment. In low-dose MTX-treatment drug interactions do not play a major role with normal renal function. Concomitant application of nonsteroidal antirheumatic drugs can delay MTX elimination and increase toxicity. We therefore avoid giving these drugs on the day of MTX-administration as far as possible. | |
| 2803323 | Electron microscopic analysis of sequential liver biopsy samples from patients with rheuma | 1989 Oct | We used electron microscopy (EM) to analyze 52 biopsy samples from 22 patients who were receiving long-term weekly oral doses of methotrexate (MTX) for the treatment of rheumatoid arthritis. Forty-eight biopsy samples were obtained after 2-6 years of continuous treatment, and 4 samples were obtained before treatment was begun. Specimens were graded for neutral fat, secondary and tertiary lysosomes, and smooth endoplasmic reticulum (SER) in hepatocytes, and for collagen in the perisinusoidal space (Disse's space). We examined the correlations between the EM findings and the light microscopic (LM) findings in the same biopsy specimens, and between the EM findings and the results of simultaneous monthly measures of aspartate transaminase, alkaline phosphatase, bilirubin, and albumin levels, as well as history of alcohol consumption before MTX treatment and monthly assessments of clinical status during the course of treatment. The presence of collagen was minimally increased in these sequential biopsy samples, whereas fat, lysosomes, and SER were decreased. The SER decrease was statistically significant. EM findings of collagen in the space of Disse did not correlate with early fibrotic changes observed with LM. Thus, after as long as 6 years of weekly oral treatment with MTX, hepatic ultrastructural changes are minimal and are not clinically significant. The use of EM for sequential biopsy studies allows the quantitation of long-term hepatic changes that may be more limited than the impression gained after LM analysis. | |
| 3555510 | Low-dose methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. | 1987 Apr | Forty-two patients with definite or classic rheumatoid arthritis entered a prospective 24-week, double-blind, parallel clinical trial, followed by an 18-month open phase. All subjects had active synovitis that was unresponsive to nonsteroidal antiinflammatory medications and conventional slow-acting antirheumatic drugs. Initial treatment with azathioprine (AZA), 100 mg/day, or methotrexate (MTX), 10 mg/week, orally, was adjusted at predefined intervals. Both treatment groups showed statistically significant improvement at week 24, compared with baseline status, in all 9 clinical outcome variables. There were no apparent statistically significant differences in these outcome variables between the 2 treatment groups. There was a trend toward a more marked and rapid improvement in the MTX-treated group. Radiologic evidence of progression of joint damage was similar in both treatment groups at 24 and 52 weeks. Four of the 42 patients (2 receiving MTX and 2 receiving AZA) discontinued the study because of side effects, and 1 MTX-treated patient withdrew because of personal reasons. Outcome measures at week 52 (open phase) were not statistically different from those at week 24. Twenty-three patients were still taking the medication at week 104. We found that AZA and MTX were similarly effective in the treatment of rheumatoid arthritis, and that this beneficial effect was maintained for up to 2 years in most patients. | |
| 2597212 | Elevated mean corpuscular volume as a predictor of hematologic toxicity due to methotrexat | 1989 Dec | Retrospective analysis of 23 rheumatoid arthritis patients receiving low-dose methotrexate (MTX) demonstrated an association between the mean corpuscular volume (MCV) and hematologic toxicity. All 6 patients who developed hematologic toxicity were folate deficient, and 4 of 6 had marked macrocytosis. Furthermore, the mean MCV of the patients who developed toxicity was significantly higher than that of the controls without toxicity (P less than 0.02). This difference in MCV was associated with an increased probability of developing toxicity with time (P less than 0.005). These results suggest that sustained elevation in the MCV may be a predictor of impending hematologic toxicity due to folate depletion. | |
| 2273459 | Effect of aspirin and sulindac on methotrexate clearance. | 1990 Sep | The pharmacokinetics of low dose methotrexate (MTX) were evaluated in 12 rheumatoid arthritis patients in the presence and absence of steady-state levels of salicylic acid (ASA) and sulindac (SU). Using a Latin square design, patients were given MTX plus ASA (mean 3.4 g/day), MTX plus SU (mean 400 mg/day), or MTX alone. On a background of at least one year of regular MTX therapy, patients received 10 mg/m2 MTX iv (mean 17.8 mg) given after at least 2 weeks of treatment with each of the above regimens. Plasma concentrations of MTX and 7-hydroxymethotrexate (7-OH-MTX) were measured using HPLC. No differences in MTX clearance (Cl) were found comparing MTX alone, MTX + ASA, and MTX + SU. However, if one particular subject that had a very low clearance when receiving MTX alone was excluded, there was a statistically significant decrease in MTX clearance when either ASA or SUL were present. It is also noteworthy that ASA significantly increased the exposure of the subject to 7-OH-MTX and, to a lesser extent, so did sulindac. Since 7-OH-MTX has been shown to be an active metabolite when given for cytotoxic effects at higher doses and because it has been show to be nephrotoxic at doses a thousand-fold greater than used in rheumatoid arthritis, nonsteroidal anti-inflammatory drugs should be used cautiously with MTX until further large scale safety studies are conducted. The data indicate that if a clinically significant interaction were to occur, ASA is more likely than SU to interact with MTX. | |
| 2487701 | Treatment of rheumatoid arthritis. | 1989 Sep | The management of the rheumatoid patient involves the considered use of pharmacologic agents as therapies to induce symptomatic relief and to reduce disease activity. Aspirin and nonsteroidal antiinflammatory drugs are used initially to lessen the degree of pain and swelling associated with the inflammatory disease process. The aggressive institution of second-line therapy, previously known as disease-modifying antiinflammatory rheumatic drugs, is advocated to modify the disease course itself. These second-line treatments include antimalarials, gold salts, methotrexate, d-penicillamine, and azathioprine. Randomized placebo controlled trials have demonstrated the efficacy of these compounds in this illness. Improvement in standard parameters of disease activity (number of painful and swollen joints, duration of morning stiffness, erythrocyte sedimentation rate) can be related to the therapeutic value of second-line agents. Whether they modify radiographic progression is under rigorous study. Newer therapies under research investigation include sulfasalazine, cyclosporin A, and combination therapy. | |
| 2799349 | [Severe acute pneumopathy following low-dose methotrexate therapy in chronic polyarthritis | 1989 Oct 14 | A 70-year-old patient with a history of rheumatoid arthritis was hospitalized for severe acute pneumonitis after 36 weeks of treatment with low-dose methotrexate (7.5 mg/week). High dose corticotherapy and assisted ventilation were necessary to obtain a clinical response. Medical history, clinical signs, laboratory findings. X-ray films of the chest and special investigations suggest the diagnosis of acute low-dose methotrexate pneumonitis. | |
| 2066953 | Severe pancytopenia in a patient taking low dose methotrexate and probenecid. | 1991 Apr | A patient with rheumatoid arthritis developed life-threatening pancytopenia resulting from low dose oral methotrexate (MTX) toxicity potentiated by probenecid. Clinically significant drug interactions are not frequently cited as risk factors for MTX hematologic toxicity. As low dose MTX is gaining increasing popularity in rheumatologic practice, these potentially serious interactions should be considered. | |
| 3196365 | Hepatic ultrastructure after methotrexate therapy for rheumatoid arthritis. | 1988 Dec | Twenty-six patients receiving long-term oral methotrexate (MTX) therapy for rheumatoid arthritis (24 patients) or psoriasis (2 patients) were prospectively evaluated for alterations in liver morphology by light microscopy, electron microscopy, and immunofluorescence microscopy. Although only 4 MTX-treated patients had light microscopic evidence of mild fibrosis, all had evidence of collagen deposition in the space of Disse near Ito cells and changes in hepatocyte lysosomes on electron microscopy. These findings were absent from control livers. Fibrinogen, fibronectin, and type IV collagen were identified by immunofluorescence in both MTX-treated patients and controls. We conclude that long-term MTX therapy for rheumatoid arthritis is associated with alterations in hepatic ultrastructure, including collagen deposition in the space of Disse and changes in hepatocyte lysosomes. | |
| 3280790 | Severe reversible interstitial pneumonitis induced by low dose methotrexate: report of a c | 1988 Jan | A patient treated with 7.5 mg methotrexate/week (MTX) for rheumatoid arthritis (total dose 300 mg) developed high fever, dry cough and progressive dyspnea and hypoxemia due to a severe interstitial pneumonitis. MTX was discontinued and an infectious etiology was ruled out by cultures, serology and lung biopsy. Corticosteroids administered intravenously in high dose led to a dramatic improvement and a complete amelioration of all symptoms and signs. Pulmonary toxicity is a rare adverse effect of low dose MTX therapy and a review of the literature reveals 6 additional cases. Since MTX induced pneumonitis is a potentially fatal, yet completely reversible, disease, attention should be paid to even mild early respiratory symptoms in patients treated with low dose MTX and patient monitoring should include pulmonary function tests. | |
| 2225539 | Methotrexate and trimethoprim-sulphamethoxazole--a potentially hazardous combination. | 1990 Sep | A 74-year-old woman had been treated with methotrexate over 2 years for rheumatoid arthritis. She was admitted to the hospital because of non-healing leg ulcers. After being treated with trimethoprim-sulphamethoxazole for a urinary-tract infection, she developed severe pancytopenia, followed by pneumonia and septic shock. The patient died shortly after. Concomitant treatment with methotrexate and sulphonamides should be strongly discouraged. | |
| 1673721 | Toxicity profiles of disease modifying antirheumatic drugs in rheumatoid arthritis. | 1991 Feb | The toxicity profiles of 7 disease modifying antirheumatic drugs (DMARD) (hydroxychloroquine, intramuscular (im) gold, D-penicillamine, oral gold, methotrexate (MTX), azathioprine and cyclophosphamide) were evaluated in 2,479 patients with rheumatoid arthritis consecutively enrolled at 5 centers in the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) program. Incidence rates for side effects are reported as events/1000 patient-years. Our descriptive study revealed an individual profile of prevalent toxicities for each drug. Oral gold was characterized by substantial lower gastrointestinal (GI) toxicity (diarrhea 391 events/1000 patient-years, loose bowel movement 148, lower abdominal pain 76), MTX by hepatotoxicity (47) while D-penicillamine had the only clinically significant incidence of altered taste (40). MTX users reported the most mucosal ulcers (87), followed by oral gold (76), im gold (55) and D-penicillamine (38). Rash was frequently seen with gold compounds and D-penicillamine, while upper GI toxicity was common with immunosuppressive agents. Cyclophosphamide had 48% discontinuations within 6 months. MTX had the lowest discontinuation rate in the first 6 months, but then showed little difference from im gold. A preliminary similarity index was developed to compare the toxicity profiles of various DMARD. Close similarities were found between toxicity profiles of im gold and D-penicillamine, and between azathioprine and MTX. Oral gold had a unique toxicity pattern. Knowledge of these different toxicity patterns can enable more appropriate selection of agents for particular patients. | |
| 3279962 | Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. | 1988 Feb | Twenty-six patients with severe rheumatoid arthritis who had completed a randomized crossover trial of methotrexate elected to continue to receive the drug in a long-term prospective study. At 36 months, 16 patients remained in the study. Over this period of time, significant improvement was noted in the number of painful and swollen joints, physician and patient global assessments, erythrocyte sedimentation rate, and prednisone dose. Adverse reactions occurred in 16 patients (62%), including nausea, alopecia, headache, stomatitis, herpes zoster, and diarrhea. Mild leukopenia (3 patients), thrombocytopenia (3 patients), and elevated transaminase levels (8 patients) resolved with temporary drug discontinuation. No patient withdrew due to drug toxicity. Liver biopsy specimens in 17 patients after 24 months of treatment showed no evidence of fibrosis or cirrhosis. A significant increase in the percentage of T3 and T4 blood cells and increases in lymphocyte proliferation to concanavalin A and purified protein derivative of tuberculin were found after 2 years of therapy. Our findings indicate that methotrexate has remained effective over 36 months of therapy, with acceptable toxicity levels and no evidence of systemic immunosuppression. | |
| 2367474 | [Pneumonitis as a complication of low-dose methotrexate therapy in chronic polyarthritis]. | 1990 Feb | Pneumonitis has been reported to be a rare complication of low-dose MTX treatment. This paper describes a 62-year-old male patient in whom clinically successful low-dose treatment was applied. After six months of treatment, a gradually progressive pulmonary symptomatology developed and abruptly deteriorated. Radiological examination revealed interstitial and intra-alveolar densifications; functional analysis revealed partial respiratory failure. The histological finding of interstitial lymphocytic infiltration with giant cells and a chronic intra-alveolar pneumonia, with bacteriological detection of E. coli and Proteus vulg. in the BAL fluid, confirmed the suspected diagnosis of primary MTX-induced pneumonitis with secondary bacterial superinfection. In view of the fact that the literature does not seem to contain unequivocal definition, it is urgently recommended that unequivocal criteria be established. | |
| 1862580 | [Felty's syndrome]. | 1991 Jul 8 | Felty's syndrome (FS) consists of the triad: rheumatoid arthritis (RA), leukopenia and splenomegaly. FS occurs in approximately 1% of patients with RA. In this syndrome, the risk of infection is increased and anaemia, thrombocytopenia and cutaneous ulcers are more frequently observed. The literature is reviewed on the basis of a case history. The pathogenesis is unknown but is probably multifactorial. Cell antibodies, increased occurrence of immune complexes, inhibited neutrophil production, altered neutrophil distribution and reduced neutrophil function have been observed. The main indication for treatment is present if the patient has severe neutropenia (less than 0.1 x 10(9)/l) and repeated infections. Various methods of treatment are available. The most important are: gold, low-dose methotrexate, lithium, methylprednisolone pulse therapy, penicillamine and splenectomy. According to the literature, conventional steroid treatment cannot be recommended. | |
| 3449308 | Low dose pulse methotrexate in rheumatoid arthritis: an 8-year experience with hepatotoxic | 1987 Dec | The clinical utility of standard liver function tests for monitoring low dose pulse methotrexate therapy is reviewed in 163 rheumatoid arthritis patients over an eight-year period. Abnormalities of hepatic enzymes were seen in 58% of patients but led to cessation of therapy in only 5%. Moderate alcohol intake did not affect the frequency of liver test abnormalities. Abnormalities were seen more frequently in patients with longer duration of methotrexate therapy and in those with higher total dose. There was no correlation between liver test abnormalities and day of serum sampling relative to day of methotrexate dosing, nor was a correlation seen between liver test abnormalities and total weekly dose of methotrexate. Methotrexate has been demonstrated to be an effective drug in the treatment of rheumatoid arthritis. The clinical utility of standard liver tests to predict the potential for hepatotoxicity is questionable. | |
| 2920047 | Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. | 1989 Feb | Twenty-nine patients with active rheumatoid arthritis receiving long-term oral weekly methotrexate (MTX) therapy were studied to determine the extent of their hepatic architectural changes. Liver biopsies (n = 101) were performed in all patients before the initiation of MTX therapy, after 2 years, and annually thereafter (mean duration of therapy 53 months). The hepatic histologic grade (5-point scale) in 25 patients increased (worsened) (mean +/- SEM change 0.84 +/- 1.02; P = 0.001). Fibrosis, confirmed by trichrome staining, developed in 14 of 27 patients (52%). A history of alcohol consumption prior to starting MTX correlated significantly with subsequent worsening of the liver biopsy grade (r = 0.55, P = 0.0054). Alcohol intake prior to study entry, elevated weight at MTX initiation, and dose and duration of MTX were significantly associated with the development of fibrosis. Elevations in serum aspartate aminotransferase levels at 29-53 months of therapy correlated with the increase in hepatic histologic grade at the 3-year biopsy (r = 0.50, P = 0.04) and 4-year biopsy (r = 0.58, P = 0.03). We conclude that long-term MTX therapy in rheumatoid arthritis patients results in a statistically significant worsening in hepatic histologic grade, with common development of mild fibrosis. We do not consider these changes to be clinically significant at present. |