Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7939138 | Tolerability of methotrexate starting with 15 or 25 mg/week for rheumatoid arthritis. | 1994 | The objective of the present study was to assess the rate of side-effects and dose-limiting toxicity in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX) at an initial dose of 15 or 25 mg/week. One hundred and eighty-five patients with active RA were enrolled into a prospective non-blind trial over 12 months and randomized to start at a dose of 15 mg/week with subsequent increases if necessary (group A) or 25 mg/week with subsequent dose reductions according to effect (group B). With 168 patients eligible for evaluation 74% of patient in group A and 73% of patients in group B were on MTX after 12 months. Withdrawal due to side-effects amounted to 16% of patients in group A and 18% in group B, and decreases in dose due to side-effects amounted to 10% in group A and 9% in group B. The higher dose of MTX elicited a significantly higher rate of gastrointestinal side-effects (28% versus 17%, P < 0.05) and a tendency towards a higher rate of liver enzyme elevations (47% versus 39%). The frequencies of other side-effects did not differ significantly between the groups. We concluded that starting MTX treatment at a dose of 25 mg/week was associated with a higher rate of minor but not major toxicity as compared with 15 mg/week. With this profile of tolerability it is possible to examine the therapeutic potential of MTX doses exceeding 15 mg/week. | |
| 7869306 | Combination therapy of cyclosporine with methotrexate and gold in rheumatoid arthritis (2 | 1994 Nov | OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporine A (CyA) in combination with gold and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Twenty patients with RA with partial response to oral MTX and 20 patients with partial response to im gold had CyA added to their regimen for 6 months, withdrawn over 2 months and the patients monitored for 4 months. RESULTS: There was a significant improvement in joint count, joint score, joint swelling, grip strength and joint pain in patients taking the combination with no significant increase in adverse reactions. CONCLUSION: CyA in combination with gold or MTX may, over a 6 month period, increase efficacy in patients with refractory RA without significant increase in toxicity. | |
| 8229232 | Comparison of methods for identifying early methotrexate-induced hepatotoxicity in patient | 1993 Nov | Hepatotoxicity may complicate therapy with methotrexate in patients with rheumatoid arthritis. Prevention of cirrhosis may depend upon early identification of liver damage, usually accomplished by serial biopsy. To determine the adequacy of noninvasive methods for identifying hepatotoxicity, 22 sets of data were obtained in patients undergoing therapy with methotrexate for rheumatoid arthritis. Comparisons were made between liver biopsy, hepatocellular enzymes and two noninvasive radioisotopic methods that have been shown to be abnormal in hepatocellular disease: the rate constant of excretion of the 14C-aminopyrine and the time from injection to peak hepatic activity of 99mTc-diisopropylimidodiacetic acid. The hepatocellular enzymes and the time-to-peak-activity of diisopropylimidodiacetic acid were not useful predictors of methotrexate-induced hepatotoxicity. The aminopyrine breath test was abnormal in approximately half the patients with hepatotoxicity but showed poor specificity. Noninvasive methods remain inferior to biopsy for the detection of mild to moderate methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis. | |
| 8036521 | Low-dose methotrexate in rheumatic diseases--efficacy, side effects, and risk factors for | 1994 Apr | Controlled trials and observational studies have shown low-dose methotrexate (MTX) to be a second-line agent of high potency with a favorable profile of safety and tolerability in the treatment of rheumatoid arthritis (RA). Its risk-benefit ratio in psoriatic arthritis is less well documented. Preliminary reports on its beneficial effects in other disorders, including the systemic manifestations of RA, other spondyloarthritides, and collagen vascular diseases, merit more detailed examination. Gastrointestinal intolerance and hepatic enzyme elevation are the most frequent side effects of MTX; life-threatening events such as severe hemocytopenia and MTX pneumonitis are rare and amenable to prevention by recognizing risk factors and premonitory signs. Hepatotoxicity does not appear to be a major limiting factor in RA patients over the first 2 to 3 years of MTX therapy; its impact on long-term tolerance remains to be clarified. | |
| 9033614 | [Non-cancer uses of methotrexate]. | 1996 Dec 14 | Methotrexate, used for nearly 40 years as an antimetabolite for cancer therapy, also has indications in dermatology, rheumatology and pneumology. When given at low dosage, it has an antiinflammatory effect although the mechanism is not totally understood. Numerous therapeutic trials have been performed in chronic inflammatory diseases such as rheumatoid arthritis in the adult, juvenile polyarthritis and corticosteroid-dependent asthma. Methotrexate is effective in severe resistant forms of rheumatoid arthritis and is used either alone or in combination with other drugs as first intention therapy because of the good tolerance, patient compliance and ease of use. The beneficial effect in severe corticosteroid-dependent asthma remains to be demonstrated. It has also been used in severe forms of psoriasis and may be useful in other diseases with an autoimmune component. Other less common indications including Crohn's disease, ectopic pregnancy and pregnancy termination require confirmation. Tolerance and compliance are generally good, even for prolonged treatments and undesirable effects are almost always reversible at withdrawal. | |
| 8572492 | [Cutaneous pseudolymphoma during treatment of rheumatoid polyarthritis with low-dose metho | 1995 | INTRODUCTION: Over the last three years, there have been over twenty case reports of lymphoma in patients given low-dose methotrexate for rheumatoid arthritis. We observed the first case of cutaneous pseudolymphoma. CASE REPORT: A 56-year-old man had been treated with methotrexate (15 mg/day) for 6 years due to rheumatoid arthritis. He developed three isolated papulonodular ulcerations on the limbs. The histology and immunohistochemical examinations demonstrated T and B lymphoplasmocyte infiltration without epidermotropism nor destruction of the annexes. Immunolabelling for anti-Epstein-Barr virus was negative. There was a IgG lambda type monoclonal hypergammaglobulinaemia, Bence-Jones proteinuria and an increase in beta 2-microglobulin. The thoracoabdominal scan, bone marrow biopsy and gallium scintigraphy were normal. There was no sign of a Gougerot-Sjögren syndrome nor of a Felty syndrome. The skin lesions and the Bence-Jones proteinuria disappeared rapidly after withdrawal of methotrexate. There has been no recurrence with a follow-up of 16 months. DISCUSSION: The diagnosis of pseudolymphoma was retained on the basis of the clinical features, the histological and immunohistochemical evidence and especially on the clinical course after methotrexate withdrawal, i.e. spontaneous regression of the lesions within 3 weeks. A similar course has been observed in three cases of lymphocyte proliferation suggesting that this immunosuppressor would be the most probable causative agent. Lymphocyte proliferation, mainly B-cell lymphomas in haematopoietic organs occurring under methotrexate administration have occurred mainly in patients with rheumatoid arthritis. Three cases have also been described in patients with dermatomyositis, but none have been reported in patients with psoriasis. This would suggest that cofactors involved in these autoimmune diseases could also have an effect: immunodepression, potentialization due to associated treatment (corticosteroids), Epstein-Barr virus... CONCLUSION: Data on these observations should be combined in order to analyse the question of the safety of low-dose methotrexate in these patients. | |
| 8350329 | Low dose leucovorin does not interfere with the efficacy of methotrexate in rheumatoid art | 1993 Jun | OBJECTIVE: To determine if simultaneously administered low dose leucovorin interferes with the efficacy of methotrexate (MTX). METHODS: An 8-week double blind placebo controlled study of leucovorin (1 mg) in 16 patients with rheumatoid arthritis receiving chronic MTX was performed at a single academic center. RESULTS: A flare of disease activity was not observed. Clinical variables of arthritis activity did not change in the leucovorin treated population. CONCLUSIONS: Low dose leucovorin when taken simultaneously with MTX did not interfere with the efficacy of MTX in a short term 8 week trial. | |
| 8894364 | The frequency and clinical characteristics of methotrexate (MTX) oral toxicity in rheumato | 1996 Sep | To assess the frequency and clinical characteristics of methotrexate (MTX) oral toxicity in rheumatoid arthritis (RA) patients, 51 RA patients receiving MTX and 46 RA patients not receiving MTX were studied. A questionnaire, the credibility of which was tested on four separate patient groups including a group with Behcet's Syndrome, was used as a tool to determine the prevalence of stomatitis by a blind observer. In this first controlled study of the oral toxicity of MTX, prevalence of stomatitis was found in 37.2% in the group taking MTX and 19.5% in the group not taking MTX (P = 0.054). No statistical differences were detected with respect to number, duration, frequency, and site of stomatitis. Two of the 51 MTX taking patients temporarily reduced their MTX dosage and only one patient temporarily terminated MTX treatment. MTX and toxicity is usually of no major clinical concern in the treatment of RA. | |
| 8465132 | [If I had chronic polyarthritis--current ideas on basic therapy]. | 1993 Mar 23 | Rheumatoid arthritis (RA) is a chronic inflammatory disorder of largely unknown etiology and complex multifactorial pathogenesis. To date, the medical management has been less than optimal and has consisted primarily of drugs that modulate the acute inflammatory process. Over the years a treatment program referred to as the classical therapeutic pyramid has evolved. A new concept and a controversial one in therapy of RA is that already at the time of definitive diagnosis, a more concerted effort towards vigorous treatment using second-line drugs such as methotrexate, should be made. It is very likely that over the next 5 years interventions such as monoclonal antibodies directed against predetermined T-cell subpopulations and anti-cytokines such as TNF-alpha binding proteins will evolve as new concepts in therapy of RA. | |
| 1439483 | Interleukin-8 in inflammatory rheumatic diseases: synovial fluid levels, relation to rheum | 1992 | The content of interleukin-8 (IL-8) in the synovial fluid and its production by blood and synovial fluid mononuclear cells (PBMC and SFMC) was compared in rheumatoid arthritis (RA) and various other inflammatory rheumatic disorders. The study included 125 patients and 20 healthy individuals. The highest concentrations of IL-8 were found in the synovial fluids and culture supernatants of PBMC and SFMC from patients with seropositive RA. Only PBMC from seropositive patients, and not from other rheumatic diseases, exhibited significant spontaneous release of IL-8 that correlated with serum IgM rheumatoid factor titers. Gold sodium thiomalate (GST) and methotrexate (MTX) inhibited the spontaneous and stimulated IL-8 production by PBMC by 55-86% at 50 and 10 micrograms/ml, respectively. Two main conclusions were drawn: (1) rheumatoid factors appeared to be a major cause of enhanced IL-8 production in seropositive RA, and (2) inhibition of IL-8-mediated neutrophil migration and activation could be part of the mechanism of action of GST and MTX. | |
| 8969553 | [Adverse effects of low-dose methotrexate therapy in rheumatoid arthritis]. | 1996 Oct | To analyze the possible adverse effects of low dose methotrexate (MTX) therapy, 276 patients with rheumatoid arthritis (RA) were examined retrospectively. One hundred and seven patients (39%) experienced 113 adverse events : 57 showed liver dysfunction, 24 gastrointestinal complaints, 13 cutaneous symptoms, 6 respiratory symptoms, and 6 malignancies. Interestingly, 3 patients developed a dry cough without infiltration nor interstitial shadow on chest X-ray. The cough was rapidly resolved by discontinuation of MTX, but it recurred in 1 patient when MTX was re-administered. This finding might suggest a close association between MTX administration and the occurrence of dry cough. Of the 6 patients with malignancies diagnosed during MTX therapy, 2 showed malignant lymphoma, 2 lung cancer, 1 breast cancer and 1 colon cancer. MTX might have an oncogenic potential in RA because the coincidence rate, especially with respect to lymphoma, was significantly higher than estimated in a normal population. | |
| 8793260 | Sustained cough in methotrexate therapy for rheumatoid arthritis. | 1996 May | Sustained cough is a frequent complaint in methotrexate (MTX) treatment for rheumatoid arthritis and can be a symptom of incipient MTX-induced pneumonitis. This study was performed to characterize MTX-associated cough clinically and to clarify by which means this condition can be distinguished from incipient MTX pneumonitis. Three patients with MTX-induced pneumonitis and 10 patients with sustained cough unassociated with pneumonitis were examined clinically, by pulmonary function testing, and bronchoalveolar lavage (BAL). In MTX pneumonitis, cough was associated with progressive dyspnoea, constitutional symptoms, impaired pulmonary function, and interstitial infiltration of variable degree by chest X-ray. BAL cytology invariably showed lymphocytic alveolitis while transbronchial biopsy revealed active interstitial inflammation in only one patient. Ten patients had sustained, nonprogressive cough in the absence of constitutional symptoms, progressive dyspnoea and impaired pulmonary function. Neither X-ray nor BAL nor transbronchial biopsy revealed any evidence of interstitial lung disease. In the majority of these patients, cough abated with symptomatic treatment with or without temporary discontinuation of MTX. It is concluded that MTX-associated cough can be a reflection of isolated airway disease. Clinically, absence of constitutional symptoms, impaired pulmonary function, and interstitial infiltration on X-ray distinguished this condition from incipient MTX pneumonitis. Cough without pulmonary parenchymal involvement appears to result from an irritant effect of MTX on the airways. | |
| 8779792 | [Pancytopenia and Pneumocystis carinii pneumonia associated with low dose methotrexate pul | 1996 Jun | Low-dose weekly pulse MTX therapy is effective for rheumatoid arthritis (RA) and is used for patients with RA who are unresponsive to conventional disease-modifying antirheumatic drugs (DMARDs). We used MTX to a 62-year-old man with RA who had received DMARDs for 5 years. MTX was effective for RA but after 12 weeks MTX therapy started, he complicated pancytopenia and developed Pneumocystis carinii pneumonia. We reviewed all RA patients reported in Japan and in the world from 1965, complicated with Pancytopenia (37 cases) and Pneumocystis carinii pneumonia (13 cases) after MTX therapy. Results were as following; (1) MTX should not be used with TMP-SMX. and risk factors for pancytopenia were (2) age over 60 years old (3) renal hypofunction (4) use of NSAID. | |
| 8215627 | Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis. | 1993 Aug | OBJECTIVES: The aim of this investigation was to study the glomerular and tubular effects of low doses (15 mg) of methotrexate in patients with rheumatoid arthritis with and without combined treatment with aspirin (2 g single dose). METHODS: Renal function was measured by the plasma clearance of EDTA labelled with chromium-51 (51Cr-EDTA) and mercaptoacetyltriglycine labelled with technetium-99m (99mTc-MAG-3). RESULTS: Clearance of 51Cr-EDTA was reduced from 98 (6) to 87 (5) ml/min (mean (SEM)) for patients receiving methotrexate only and further reduced to 76 (5) ml/min for patients receiving methotrexate and aspirin. This effect was reversible as 51Cr-EDTA increased to 85 (6) ml/min during continued treatment with methotrexate alone. Clearance of 99mTc-MAG-3 also decreased from 366 (18) to 315 (17) ml/min in patients receiving methotrexate alone and further to 295 (17) ml/min during treatment with aspirin and methotrexate. Continued treatment with methotrexate alone resulted in a further decrease in the 99mTc-MAG-3 clearance to 253 (17) ml/min. CONCLUSIONS: The study shows that treatment with low doses of methotrexate particularly when combined with aspirin affects glomerular and tubular function. These effects may be of clinical importance and renal function should therefore be monitored with more sensitive methods than serum creatinine as this may not reflect these changes. | |
| 8646434 | Occurrence of pulmonary complications during methotrexate therapy in rheumatoid arthritis. | 1996 May | Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The aim of this retrospective study was to evaluate, during a 6 yr period, the prevalence and severity of bronchopulmonary side-effects in RA patients treated with MTX. A cohort of 130 RA in-patients (106 women, 24 men) treated with MTX was studied for the occurrence of respiratory adverse events. Adverse bronchopulmonary side-effects were observed in 12 patients (two men, 10 women), with a mean disease duration of 15 yr. Only three patients had previously suffered from pulmonary disease. MTX treatment duration was between 1 month and 4.5 yr. The diagnosis was that of hypersensitivity pneumonitis (HSP) in four cases, non-HSP pneumonitis in five patients with one case of Pneumocystis carinii infection, and bronchitis in three cases. The initial respiratory symptoms were not discriminatory between the different conditions. Risk factors were not identified for the occurrence of HSP. HSP always occurred in the first 5 months of treatment. Two patients with HSP died, and another patient with opportunistic infection underwent tracheostomy. HSP represents a potentially lethal side-effect in RA patients treated with MTX. Improved education of patients and physicians should certainly lead to a reduction of both the prevalence and severity of pulmonary side-effects during MTX therapy in RA. | |
| 8203949 | Infection rate and use of antibiotics in patients with rheumatoid arthritis treated with m | 1994 Apr | OBJECTIVE: To investigate prospectively the frequency and type of infections and the use of antibiotics among patients with rheumatoid arthritis (RA) on methotrexate (MTX) and patients with RA without MTX. METHODS: Every three months for one year 77 patients on MTX and 151 patients without MTX were asked about infections and the use of antibiotics by means of a standardised questionnaire. Medication was checked with the pharmacist. RESULTS: In the MTX group there were significantly more infections and more antibiotic therapy. The relative risks for patients on MTX of infection or antibiotics use were 1.52 (95% Confidence Interval (CI) 1.04-2.22) and 1.49 (95% CI 1.04-2.13), respectively. The relative risk of MTX for respiratory tract infections was 1.43 (95% CI 0.96-2.14) and for skin infections 2.19 (95% CI 1.45-3.31). The increased risks could only partly be explained by differences in disease severity and were not related to either duration of MTX therapy or use of prednisone. Three patients in the MTX group had herpes zoster versus one in the control group. CONCLUSIONS: Treatment with MTX increases the rate of infection and thus the use of antibiotics but does not lead to serious complications necessitating discontinuation of the drug. | |
| 8098643 | Porphyria cutanea tarda associated with methotrexate therapy. | 1993 May | A 69-year-old lady with RA developed porphyria cutanea tarda 2 weeks following initiation of methotrexate therapy. The clinical and laboratory features are described. | |
| 1642652 | Comparison of azathioprine, methotrexate, and the combination of both in the treatment of | 1992 Aug | OBJECTIVE: To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations. CONCLUSION: Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment. | |
| 7612033 | End-stage liver disease developing with the use of methotrexate in heterozygous alpha 1-an | 1995 Jul | We report a case of cirrhosis developing in a man who was heterozygous for alpha 1-antitrypsin deficiency and who was receiving methotrexate for severe rheumatoid arthritis. The alpha 1-antitrypsin phenotype PiMZ has been associated with cryptogenic cirrhosis. Our patient had no biochemical or histologic evidence of chronic liver disease during the first year of receiving methotrexate. We postulate that the PiMZ state may result in enhanced susceptibility to methotrexate-induced hepatic toxicity and should be screened for if liver function abnormalities occur during methotrexate therapy. | |
| 8507221 | Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthr | 1993 Jun | OBJECTIVE: To determine whether the side effects of methotrexate can be decreased by the concurrent use of leucovorin, without affecting the efficacy of the methotrexate. METHODS: We conducted a multicenter randomized, double-blind, placebo-controlled trial of leucovorin administration, 2.5-5.0 mg orally, to be given 24 hours after the single, weekly, oral dose of methotrexate. Every 3 weeks for 52 weeks, patients were evaluated for rheumatic disease activity and side effects. Dosage adjustments for both methotrexate and leucovorin were made as needed, according to a defined protocol. The primary outcome evaluated was the frequency of study withdrawals because of side effects and/or inefficacy. Secondary outcomes evaluated included the frequency of side effects and the relative efficacy of methotrexate in the leucovorin and placebo treatment groups. RESULTS: Ninety-two evaluable patients were analyzed (44 took leucovorin and 48 placebo). Twenty-two patients withdrew early because of side effects unresponsive to our protocol, and 1 because of inefficacy; 17 had been taking placebo and 6 had been taking leucovorin (35% versus 14%, P < 0.02). The number of visits during which side effects were reported was reduced by almost 50% in the leucovorin treatment group (P < 0.001). There were significant reductions in the frequencies of all common side effects. At 52 weeks, disease activity was similar in both patient groups. CONCLUSION: The methotrexate-leucovorin protocol used significantly reduces common side effects of methotrexate therapy without significantly altering efficacy. |