Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8817757 | Pneumocystis carinii pneumonia in rheumatoid arthritis patients treated with methotrexate. | 1996 Jun | Use of methotrexate to treat rheumatoid arthritis is associated with pulmonary adverse effects in 3% to 5% of cases. In addition to immunoallergic lung disease, bronchitis and pneumonia due to pyogenic organisms, opportunistic lower respiratory tract infections have been reported, including, to our knowledge, 18 cases of Pneumocystis carinii pneumonia. We report two new cases of P. carinii pneumonia in methotrexate-treated rheumatoid arthritis patients. One case occurred in a 62-year-old woman with a nine-year history of seropositive rheumatoid arthritis treated for the last seven months with methotrexate, 15 mg per week, and prednisone, 10 mg/d. The other patient was a 58-year-old woman who had been diagnosed with rheumatoid arthritis 18 months earlier and had been receiving 15 mg per week of methotrexate for eight months in combination with 12.5 mg of prednisone per day. Both patients had negative tests for the human immunodeficiency virus. Symptoms consisted of fever, cough and dyspnea, with interstitial infiltrates on chest films, hypoxia, and lymphopenia (700 and 600/mm3, respectively). The diagnosis was confirmed by bronchoalveolar lavage. Both patients recovered under treatment with trimethoprim-sulfamethoxazole. An analysis of the 20 cases of P. carinii pneumonia reported to date in methotrexate-treated rheumatoid arthritis patients demonstrated a number of characteristics: the rheumatoid arthritis was of recent onset in some cases (a few months in one patient); lymphopenia was present in two thirds of cases; one-third of patients were not receiving corticosteroid therapy; the dosage and duration of methotrexate therapy varied widely, from 5 to 30 mg per week and two to 48 months; and four patients died. | |
| 8990864 | Liver cirrhosis due to methotrexate in a patient with rheumatoid arthritis. | 1996 Dec | A 49-year-old female with rheumatoid arthritis developed liver cirrhosis after a cumulative dosage of 6 g methotrexate (MTX). There were mild liver enzyme abnormalities, decreased liver synthesis function and possible signs of portal hypertension. After stopping MTX all laboratory abnormalities disappeared except for a mild thrombocytopenia. Risk factors and guidelines for monitoring liver toxicity during MTX treatment in rheumatoid arthritis are discussed. | |
| 8971231 | Methotrexate patient education: a quality improvement study. | 1996 Jun | OBJECTIVE: To determine patients' knowledge of the safe use and toxicity of methotrexate (MTX) and to define educational interventions implemented by a rheumatology nurse that improved patients' understanding of MTX therapy. METHODS: One hundred eighty-three patients from a university-based rheumatology clinic who were taking MTX completed an initial knowledge questionnaire concerning the proper use and possible toxicity of MTX. Following completion, a nurse reviewed the correct answers with each patient and provided written information on MTX. One hundred thirty-eight of these patients completed a followup questionnaire at the next visit or by mail. The questionnaires were analyzed, and a total MTX knowledge score was calculated. RESULTS: MTX knowledge improved significantly between questionnaires; mean total score (+/- SD) increased from 7.32 +/- 3.99 to 10.23 +/- 3.29 (P < 0.001). After accounting for a person's initial questionnaire score, the addition of a supplemental "MTX pocket-card" was associated with a higher score on the follow-up questionnaire (adjusted odds ration [OR] = 2.37; 95% confidence interval [CI] 1.14, 4.95; P = 0.021). Patients over age 55 were 4 times more likely to have a poorer score compared with patients under age 45 (adjusted OR = 0.23; 95% CI 0.07, 0.73; P = 0.013). CONCLUSION: Knowledge of the toxicity and safe use of MTX was significantly improved by a patient education program utilizing a rheumatology nurse. Older individuals appear to be at higher risk for knowledge deficits. A supplemental MTX pocket-card proved to be a simple but beneficial addition to our MTX educational program. | |
| 8810686 | Combination therapy with cyclosporin in rheumatoid arthritis. | 1996 Sep | The role of combination therapy in rheumatoid arthritis (RA) is increasing with the development of new treatment modalities. Past combinations of slow-acting anti-rheumatic drugs resulted in either excessive side-effects or lack of efficacy over single-agent therapy. However, refined methodology and a better understanding of the mechanism of action of newer agents have led to improved combinations, which appear more promising. In particular, in a 6 month, randomized, double-blind trial, the combination of cyclosporin (CyA) with methotrexate was found to be more efficacious than methotrexate alone, providing enhanced clinical benefit, without evidence of increased adverse events. The mean final dose of 2.97 mg/kg per day CyA in combination was lower than that required for CyA monotherapy. Further, a new formulation of CyA, with improved bioavailability, should provide enhanced efficacy and an acceptable safety profile, not only as monotherapy but also in combination with agents such as methotrexate. These developments offer new hope to patients with progressive RA, which is unresponsive to conventional therapy. | |
| 1440085 | [A case of rheumatoid arthritis complicated with pseudotumor around odontoid process succe | 1992 Oct | A 69-year-old-female with a history of rheumatoid arthritis since 1975 had suffered from dysesthesia of extremities since October 1989. Radiating pain and weakness occurred when she tried to stand up on Dec. 25 in 1989. She was admitted to our hospital in October 1990. Physical examination showed emaciation, hypesthesia of extremities, hypesthesia over the right chest and back, impaired vibration and position sense, and hyperreflexia. Laboratory findings revealed that the erythrocyte sedimentation rate was elevated to 46mm/hr, rheumatoid factor (RF) to 83.1IU/ml and CRP to 3.7mg/dl. Her blood sugar was high and she was diagnosed as having diabetes mellitus. Cervical X ray film showed atlanto-axial subluxation. A pseudotumor around the odontoid process bulging into the spinal canal and compression of the upper cervical cord was observed by MRI. In spite of administration of bucillamine (100mg/day), the size of pseudotumor did not change. Methotrexate (MTX) at a dose of 5mg/week was started in February 1991 and the pseudotumor decreased in size with a concurrent reduction of ESR, RF and CRP. However, the high intensity lesion by T2 weighed image did not change and dysesthesia persisted. The pseudotumor was thought to be due to pannus and it was revealed that MTX was effective for reduction. The persistent dysesthesia was probably due to the degeneration of the upper cervical cord, although diabetic neuropathy may also have played a role. | |
| 7812288 | [Side-effects during treatment of rheumatoid arthritis with methotrexate]. | 1994 May | Methotrexate is the drug with the highest long-term continuation rate in rheumatoid arthritis patients. However, toxicity is the main reason for methotrexate withdrawal. Most adverse effects are mild abnormalities, such as digestive symptoms, stomatitis, elevations in transaminase levels, and moderate decreases in peripheral blood cell counts. Potentially life-threatening effects include hypersensitivity pneumonitis and pancytopenia. Cirrhosis is less common than in patients with psoriasis. Opportunistic infections and Epstein-Barr virus-related lymphomas have been reported. Neurological disorders, cutaneous reactions and renal lesions have been ascribed to low-dose methotrexate. Prior renal dysfunction and concomitant administration of a number of drugs, including cotrimoxazole, have been shown to increase methotrexate toxicity. However, susceptibility to the toxic effects of methotrexate varies widely across individuals. The effectiveness of folate supplementation in preventing methotrexate toxicity remains controversial. | |
| 8100752 | Experience with a chimeric monoclonal anti-CD4 antibody in the treatment of refractory rhe | 1993 Mar | We have used a chimeric monoclonal anti-CD4 antibody (cM-T412) in a phase I trial involving patients with refractory RA. The objectives of this initial study were to evaluate the safety, immunogenicity, and biologic effects of cM-T412. Twenty-five patients with active refractory RA (all taking methotrexate concomitantly) were treated with incremental doses (10 to 700 mg) of cM-T412 in an open-label, escalating dose phase I trial. Levels of circulating CD4+ T-cells decreased rapidly post-infusion and remained significantly depressed even at 18 months following treatment. Repopulation of CD4+ T cells consisting of increased CD45RA+ (naive) and CD45RO+ (memory) CD4+ T-cells was observed in approximately 1/3 of the patients between day 14 and 6 months post-infusion. Proliferative responses of peripheral blood lymphocytes to mitogens and recall antigens were generally diminished following cM-T412 infusion, with mitogen responses normalizing more rapidly than responses to recall antigens. Adverse events during the first 6 months of follow-up included fever, often associated with myalgias, malaise, and asymptomatic hypotension; these symptoms were self-limited and appeared to correlate with transient elevations of interleukin-6. Negligible human antibody responses to the cM-T412 variable region were observed; indeed, only 2 patients developed transient low levels of antibodies reactive with cM-T412. Non-blinded assessment indicated that 43% of patients exhibited > or = 50% improvement in tender joint counts at 5 weeks, and 33% at 6 months post-infusion.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 7479260 | [Overdose of methotrexate with a fatal outcome in a patient with rheumatoid arthritis]. | 1995 Apr | A 52-year old female patient with rheumatoid arthritis (RA) had mistakenly taken 112.5 mg methotrexate (MTX) over a period of five days. As a result, extensive erosions along with necrotic changes occurred in the oral cavity, the groins and vulva mucous membrane. Haemorrhages in the gastrointestinal tract, dermal xanthochromia, interstitial pneumonia and progressive renal insufficiency, as well as hair loss, also followed. Laboratory examination showed peripheral blood agranulocytosis, a decrease in the overall number of blood platelets, anaemia, an increase in the level of transaminases and bilirubin, along with megakaryocyte deficiency. Cultivated dermal specimens initially developed bacteria, then Candida albicans. The patient died on the 22nd day after the overdose from pneumonia and extensive mycosis. | |
| 7637973 | [Experience with long term low dose methotrexate treatment in rheumatoid arthritis and art | 1995 Jul 16 | The clinical efficacy and the side effects of a long term (max. 42 months, min. 5 months) weekly pulse methotrexate treatment (10 mg/week) were investigated in 31 rheumatoid arthritis patients and in 14 with psoriatic arthritis. A reduction in the number of inflamed joints and diminished duration of morning stiffness could be observed together with a decrease of pain and of the erythrocyte sedimentation rate in rheumatoid arthritis. In patients with psoriatic arthritis the intensity of joint pain was not influenced considerable and the decrease of the erythrocyte sedimentation rate was not as great as in rheumatoid arthritis patients. Ineffectivity of the methotrexate treatment occurred in one rheumatoid arthritic patient. The methotrexate treatment could not be carried on in two rheumatoid arthritic patients because of adverse side effects. | |
| 1464074 | [Pharmacotherapy of rheumatoid arthritis in 1992]. | 1992 Oct 9 | The author presents an overview of the state of pharmacotherapy of rheumatoid arthritis in 1992. In the area of non-steroidal antirheumatic drugs attention is drawn to some problems associated with their undesirable action on the digestive tract and articular cartilage. The problem of interindividual reactivity to this group of drugs has not been resolved so far. The mechanism of their action, in particular analgetic action, is also still open. It was found that they can exert not only a central but also a peripheral action. Drugs modifying the disease have been extended by sulphasalazine, methotrexate and cyclosporin. Interest in combined treatment with these drugs is increasing as well as attitudes to the strategy of their application. The corticoid group has been extended by the preparation deflazacort which does not have a catabolic effect on osseous tissue. In the posology of corticoids pulsed treatment is gaining support. | |
| 8205370 | Methotrexate serum binding in rheumatoid arthritis. | 1994 Mar | The serum binding of methotrexate was determined by equilibrium dialysis using radiolabelled methotrexate. Methotrexate was only albumin-bound in serum. The binding was 46% in controls versus 42% in rheumatoid arthritis and 44% in cancer. Serum binding was significantly decreased by salicylate and high concentration of naproxen. Hypoalbuminemia and concomitant administration of salicylate or naproxen may influence methotrexate toxicity. | |
| 7878694 | Methotrexate in rheumatoid arthritis--a limited sampling strategy for estimation of the ar | 1994 Dec | A limited sampling strategy for determination of the area under the plasma concentration versus time curve (AUC) of methotrexate (MTX) in patients with rheumatoid arthritis (RA), treated with weekly oral doses, has been validated. Stepwise linear regression analysis was used for optimal inclusion of data points in mathematical models to estimate AUC. A new plot for evaluation of the accuracy and precision of the estimated AUC values was introduced in the present study. By plotting the ratio of determined/estimated AUC values versus estimated AUC values, the influence of number of sampling points on the precision and accuracy of estimated AUC values was easily validated. Our results show that AUC values of MTX in RA patients can be estimated from a single plasma sample at 3 h or preferably, due to increased precision, by additional samplings at 5 and 1 h. A further increase of the number of sampling points increased the precision of the AUC estimates only to a minor extent. The accuracy of the estimated AUC values was independent of the number of sampling points. A limited sampling procedure can now be used for further studies on the relationship between MTX levels and its effects. | |
| 8467620 | Lymphoma developing in a patient with rheumatoid arthritis taking methotrexate. | 1993 Mar | We report one case of non-Hodgkin lymphoma in a patient, with a 30-year history of rheumatoid arthritis, taking low dose methotrexate weekly over a 10-month period. The mild immunosuppression that occurs with methotrexate therapy probably places patients with rheumatoid arthritis at added risk of developing lymphoproliferative diseases, but coincidence cannot be excluded. | |
| 8015285 | Excess of metalloproteases over tissue inhibitor of metalloprotease may contribute to cart | 1994 Jun | BACKGROUND: In an attempt to identify the factor(s) involved in the modulation of the degradative pathway of articular cartilage, we previously reported a possible imbalance between the levels of biologically active forms of metalloproteases and tissue inhibitor of metalloprotease (TIMP) in osteoarthritis (OA) cartilage. EXPERIMENTAL DESIGN: We extended our analysis on the protein level and the synthesis of stromelysin-1, collagenase, TIMP-1, and TIMP-2 in normal, OA, and RA cartilages, and provided information on the synthesis pattern of these proteins in respect to the action of interleukin-1 (IL-1). These protein concentrations were determined by specific sandwich EIA assays. RESULTS: This study allowed us to establish that the concentration of stromelysin-1 and collagenase is elevated in both OA and rheumatoid arthritis (RA) cartilages when compared with normal, with significantly higher levels of collagenase found in OA (p < 0.0003) and RA (p < 0.0001), and of stromelysin-1 in RA (p < 0.02). In all cases, the level of stromelysin-1 significantly exceeded (a few 100-fold) the collagenase level. The cartilage TIMP-1 level was notably enhanced only in RA, whereas TIMP-2 was increased in both OA and RA cartilage. RA patients with active disease had a higher level of metalloproteases and TIMP than those patients with inactive disease. Moreover, patients taking steroids alone or in combination with methotrexate had a markedly lower metalloprotease level without any changes in the TIMP-1 level. In culture cartilage explants, the synthesis of stromelysin-1 was enhanced in RA cartilage, whereas the level of collagenase was increased both in OA and RA explants. When compared with normal patients, the TIMP-1 synthesis was essentially unchanged in arthritic explants, whereas the level of TIMP-2 was decreased in RA explants when compared to OA. IL-1 induced a statistically significant increased synthesis of metalloproteases with the highest level found in arthritic explants. IL-1 also significantly decreased the TIMP-1 synthesis in OA and RA explants, and the TIMP-2 synthesis in OA. CONCLUSIONS: This study demonstrates that stromelysin-1 is the predominant metalloprotease synthesized in human articular cartilage and that both TIMP-1 and TIMP-2 are present in this tissue. The differential regulation of metalloprotease and TIMP syntheses by IL-1 suggests that this cytokine, during inflammatory conditions, may promote cartilage degradation by creating an imbalance between the level of these enzymes and their inhibitors. | |
| 9036717 | [Does parenteral gold inhibit roentgen progression of chronic polyarthritis?]. | 1996 Sep | The retardation of radiological progression is one of the most important characteristics of a disease-modifying effect of an antirheumatic drug. For the following overview 10 trials were identified dealing with x-ray progression under treatment with parenteral gold. Nine of these trials were randomised parallel studies, one was a retrospective long-term observational study, all had a control group, in five this control group was treated with placebo, in two trials parenteral gold was compared with another DMARD (auranofin and methotrexate, respectively), in two trials different doses of gold were compared and in two trials the radiological progression during the first 6 months was compared with the following treatment period (in one of these trials gold was compared with methotrexate as well). The duration of treatment and follow-up was up to 1 year in two trials, up to 2 years in six, and over 2 years in only two studies. There is a great number of limitations in these studies: for instance, there was a large number of withdrawals who were not followed, x-rays were available for evaluation only in a relatively small proportion of treated patients in five studies, in six studies the disease duration was over 2 years at baseline, which limits the evaluability of x-ray progression for technical reasons. In one study juxta articular osteoporosis and joint swelling were evaluated; but these parameters are very difficult to evaluate in a multicenter study because of the different quality of the films. In spite of all limitations and reservations with the studies reviewed the published results indicate a reduction of radiological progression with parenteral gold treatment of rheumatoid arthritis patients: in the placebo-controlled studies outcome in the gold group was significantly better than in the placebo group. The study of the Empire Rheumatism Council failed to show a significant difference compared to the control group after 30 months, but the patients had been treated sufficiently only for 5 months. The study of Cats indicated a better outcome in the group of patients with a high gold dose, which is confirmed by the retrospective analysis of Luukkainen. In a comparison between 113 patients treated with parenteral gold and 119 patients treated with auranofin for 1 year Larsen found a significantly smaller progression in the patients treated with parenteral gold. In a patient population of 73 and 53 the difference between methotrexate and parenteral gold was too small to be detectable, but the progression curve was significantly flattened after the first 6 months, indicating a treatment effect. In a macroradiographic study the erosion surface area increased during the first 6 months of gold treatment, it did not change during the second 6 months, and decreased during the third 6 months together with healing of erosions. In conclusion, the studies reviewed in this paper indicate a disease-modifying potency of parenteral gold treatment, especially when the treatment is started early and sufficiently dosed. | |
| 8919443 | Neurologic complications after total shoulder arthroplasty. | 1996 Jan | Three hundred sixty-eight patients underwent 417 total shoulder arthroplasties between 1975 and 1989. Seventeen patients with 18 operated shoulders had a neurologic deficit after surgery. Osteoarthritis and rheumatoid arthritis were the most common diagnoses. Twelve patients (13 shoulders) had neurologic deficits localized to the brachial plexus; the upper and middle trunks were most commonly affected. Three patients had idiopathic brachial plexopathy. One patient had an exacerbation of preexisting dysesthesias in the lower trunk/medial cord distribution. Another patient had a median neuropathy at the wrist. Four patients had lesions that interfered significantly with shoulder rehabilitation and general activity; six had lesions that temporarily interfered with their scheduled rehabilitation program. All but two of these patients were monitored to a point of maximum improvement. Neurologic recovery at 1 year was graded as good in 11 shoulders and fair in five shoulders. The long deltopectoral approach leaving the deltoid attached to the clavicle and acromion was found to be significant in the development of a postoperative neurologic complication (p = 0.003). Use of methotrexate was also significant (p < 0.0001). A correlation was found between operative time and postarthroplasty neurologic complication (p = 0.02), with shorter operative times being associated with more neurologic complications. No other statistically significant risk factors were identified. In most cases the presumed mechanism of injury was traction on the plexus occurring during the operation. In most cases the prognosis for neurologic recovery was good. In this series neurologic injury after total shoulder arthroplasty did not interfere with the long-term outcome of the arthroplasty itself. | |
| 7639808 | Usefulness of the American College of Rheumatology recommendations for liver biopsy in met | 1995 Aug | OBJECTIVE: To test the usefulness and cost savings resulting from application of the new American College of Rheumatology (ACR) guidelines for assessing the risk for the development of clinically significant liver disease in rheumatoid arthritis (RA) patients treated with methotrexate (MTX). METHODS: One-hundred twelve MTX-treated RA patients were prospectively followed up for MTX hepatotoxicity and underwent liver biopsies according to modified guidelines of the Psoriatic Task Force (PTF). All biopsies were graded according to the Roenigk classification. The new ACR recommendations were then retrospectively applied to test their usefulness and cost-effectiveness in this cohort. RESULTS: Based on the PTF guidelines, 66 patients underwent liver biopsies; a total of 110 liver biopsies were performed. Two patients had biopsy-related complications. Five patients were found to have Roenigk grade IIIB or IV histologic abnormalities. The total cost for this group was $111,380. Applying the new ACR criteria, only 15 patients would have undergone liver biopsies; there would have been a total of 18 biopsies, with no complications. Four of the 5 patients with Roenigk grade IIIB or IV liver abnormalities would have been identified. One patient with insulin-dependent diabetes mellitus (IDDM) who was found to have cirrhosis (Roenigk grade IV) on liver biopsy as a result of use of the PTF guidelines would have been missed with use of the ACR guidelines. The total cost for the group receiving biopsies based on the ACR guidelines would have been $16,956. Overall, the new ACR guidelines had 80% sensitivity and 82% specificity and resulted in a cost savings of $1,430 per patient. CONCLUSION: The new ACR guidelines on MTX monitoring and biopsy surveillance appear to be clinically useful and result in considerable cost savings. However, 1 IDDM patient with significant liver histologic abnormalities would have been missed. We suggest that IDDM be added to the ACR guidelines as a risk factor for MTX hepatotoxicity. | |
| 8759491 | Duodenal mucosal ferritin in rheumatoid arthritis: implications for anaemia of chronic dis | 1996 Jul | Anaemia is a common feature of rheumatoid arthritis (RA) and other chronic diseases. Among the alterations in iron metabolism contributing to this effect is a decrease in intestinal iron absorption. The mechanism for this is unknown, but might involve a 'mucosal block' process similar to that proposed in iron overload, whereby increased expression of an enterocyte storage protein binds absorbed iron and prevents its transfer to the circulation. We examined the effect of disease-modifying therapy on ferritin expression in duodenal mucosa in RA to determine whether it may play a role in the 'mucosal block' process. Endoscopic small bowel biopsies were obtained from 11 patients with active RA both before, and 6 months after, a course of either gold or methotrexate (MTX). Mucosal ferritin levels in small bowel and stomach were measured by radioimmune assay. Duodenal mucosal ferritin decreased significantly following treatment (p < 0.05). There were no changes in gastric mucosal ferritin. The fall in duodenal mucosal ferritin correlated with indices of disease activity at start of therapy, and the largest decreases were in those patients showing the best response to treatment in terms of a fall in inflammatory markers. Site-specific changes in mucosal ferritin may underlie the altered iron absorption observed in active inflammatory disease by modifying the enterocyte 'mucosal block'. | |
| 8182625 | Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis. | 1994 Feb | OBJECTIVE: To determine if the pharmacokinetics of methotrexate (MTX) is modified by the coadministration of etodolac. METHODS: MTX (10 mg) was administered intramuscularly in the absence and presence of steady state levels of etodolac in 19 patients with rheumatoid arthritis. MTX levels were assayed by fluorescence polarization immunoassay. Concentrations of 7-hydroxymethotrexate (7-OH-MTX) were assayed by a reverse phase high performance liquid chromatography method. The unbound fraction was determined by ultrafiltration. RESULTS: When etodolac was coadministered with MTX, the highest observed concentration decreased and the mean residence time increased to become statistically significant. However, these differences are not of great clinical importance especially given that the area under the curve and clearances were unchanged. There were no significant differences in binding protein and 7-OH-MTX concentrations between MTX with and without etodolac administration. CONCLUSION: The pharmacokinetics of MTX is slightly modified by coadministration of etodolac. Moreover, no clinical toxicity was observed. | |
| 7582706 | An audit of methotrexate and folic acid for rheumatoid arthritis. Experience from a teachi | 1995 Oct | We describe an audit of 158 patients with RA treated with weekly methotrexate and 5 mg of folic acid 24 h later. Our aim was to assess the safety and efficacy of this regime in our hands compared with published clinical trials of methotrexate in RA, and to examine patient outcomes. Treatment improved ESR, but only 69% of patients continuing therapy for prolonged periods believed their arthritis to be better on treatment. Health Assessment Questionnaire and Hospital Anxiety and Depression questionnaire scores in prospectively studied patients were not significantly altered by treatment. Toxicity occurred frequently (59% in those continuing and 89% in those ceasing therapy) and cessation of therapy solely due to lack of efficacy was rare. The probability of patients continuing with methotrexate and folic acid after 1, 2, 3 and 4 yr was 87, 76, 74 and 74%, respectively, figures that are at the upper end of the reported range for methotrexate alone. |