Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8108669 | Pneumocystis carinii pneumonia associated with low dose methotrexate treatment for rheumat | 1994 | Since 1983 there have been several reports on Pneumocystis carinii pneumonia (PCP), complicating low dose methotrexate (MTX) therapy for rheumatoid arthritis (RA). Two additional cases of this opportunistic infection are reported and a review of the literature on the complication is presented. It is concluded that PCP is a serious complication of low dose MTX therapy for RA and should always be ruled out when a patient presents with pulmonary symptoms. Several factors may play a role in the occurrence of this opportunistic infection, but the exact mechanism has not yet been elucidated. | |
| 8496857 | Methotrexate therapy in rheumatoid arthritis: a life table review of 587 patients treated | 1993 Apr | To determine whether methotrexate (MTX) maintains its effectiveness in rheumatoid arthritis (RA) in the setting of community based private rheumatology practice we used life table analysis to review the combined experience of a group of these practices. Of 587 patients with RA who started to take MTX, total termination rate at 70 months was 24.4% with most terminations prompted by drug toxicity. Older age (greater than 65 years) was associated with higher rates of toxicity. Treatment termination rates varied substantially between rheumatologists. We conclude that MTX therapy for RA is well tolerated and maintains effectiveness for at least 70 months. | |
| 1616322 | Controlled trial of methotrexate versus 10-deazaaminopterin in the treatment of rheumatoid | 1992 May | A 15 week double blind controlled trial of methotrexate and 10-deazaaminopterin for the treatment of rheumatoid arthritis (RA) was performed in 26 patients. Significant improvement in all measured clinical parameters was observed in the two patient groups. The drugs were well tolerated; only one patient (10-deazaaminopterin) withdrew from the study because of side effects. It is concluded that, in the context of this relatively short clinical trial, 10-deazaaminopterin is at least as beneficial as methotrexate in the treatment of RA. | |
| 7895396 | Patient's preference regarding the option of performing unselective liver biopsy following | 1994 Nov | OBJECTIVE: This study was aimed at the evaluation of patient preferences concerning long-term methotrexate (MTX) therapy and whether or not to perform unselective liver biopsy to detect serious liver disease due to MTX therapy in rheumatoid arthritis (RA). METHODS: Seventeen literate patients with RA consecutively selected from a rheumatic disease unit and 17 rheumatologists (asked to consider themselves as RA patients) were assessed by a trained interviewer. The Bedside Decision Board instrument was used to assess the patient preference. Scenarios described the options in terms of follow-up for RA patients treated with MTX. The benefits and risks of liver biopsy, defined according to the published literature, were presented to RA patients and rheumatologists in an unbiased fashion. RESULTS: Twelve patients (71%) preferred not to be subjected to the liver biopsy within 1 month, even though they had already taken MTX for 3 years, and consequently ran the risk of development of cirrhosis in the long term. Conversely, 12 rheumatologists (71%) preferred to undergo an unselective liver biopsy. CONCLUSION: Given patients' preferences, liver biopsy following long term MTX treatment should not be performed unselectively. It can be postulated that rheumatologists did not perceive liver biopsy as an intimidating procedure or were influenced by the until recently recommended guidelines for following up patients treated with MTX. | |
| 7799392 | DC-ART classification: review of relevant clinical studies. | 1994 Sep | The proposed disease controlling antirheumatic therapy (DC-ART) definition requires that the therapy change the course of rheumatoid arthritis (RA) for at least 1 year, evidenced by (1) sustained improvement in physical function, (2) decreased inflammatory synovitis, and (3) slowing or prevention of structural joint damage. Selected studies are reviewed. All studies were at least 1 year in duration, but most did not include all 3 of the DC-ART requirements. In these studies, patients treated with placebo generally had no improvement in inflammatory synovitis and progressive structural joint damage, judged by serial joint radiographs. A minority of studies significantly favored one or another of the available agents (gold injections, D-penicillamine, auranofin, antimalarials, azathioprine, sulfasalazine, methotrexate), but the evidence for any one agent is not convincing. For future DC-ART clinical trials patients with early RA should be studied. A hybrid study design may be useful, combining an initial double blind randomized controlled clinical trial with continuing longterm observation of all withdrawals using specified clinical, radiographic, and self report assessments at regular intervals, and an intent-to-treat analysis comparing longterm response rates of the original control and experimental therapy groups. Responsive subgroups should be sought, their characteristics identified, and their responsiveness confirmed in additional trials limited to the identified subgroup. | |
| 8973868 | Chromosomal changes in rheumatoid arthritis patients treated with CPH82. | 1996 Nov | Chromosomal changes were assessed in 19 patients with rheumatoid arthritis (RA) treated with CPH82, a benzylidated podophyllotoxin glycoside, for up to one year. The frequency of chromosomal aberrations (CA) and sister chromatid exchanges (SCE) in peripheral lymphocytes increased significantly after 12 weeks of treatment and remained elevated after 48 weeks treatment in peripheral lymphocytes. The number of CA and SCE were significantly increased in CPH82 treated patients compared with the RA patients treated with other disease modifying anti-rheumatic drug (sulphasalazine, gold, D-penicillamine, azathioprine, methotrexate, cyclophosphamide). Only two patients treated with cyclophosphamide and azathioprine had changes of comparable levels. The results of this study suggest a mutagenic potential of CPH82 similar to that described for other immunosuppressive drugs and the newer podophyllotoxin derivatives, etoposide and teniposide. | |
| 8646435 | Pulmonary function in rheumatoid arthritis treated with low-dose methotrexate: a longitudi | 1996 May | Lung volumes and gas exchange were investigated prospectively in 96 patients with rheumatoid arthritis selected without regard to pulmonary disorders and treated with i.m. methotrexate (MTX) injections [mean weekly dose 13.0 mg (5th-95th percentile (5-95 PC) 7.6-20.8)]. Individual changes over time during MTX treatment [mean duration 2.9 yr (5-95 PC 0.4-5.3)] were assessed by regression analyses in each individual. Forced vital capacity (FVC) remained stable in the majority of patients [mean annual change +0.8% (5-95 PC -8.1 to +14.0) of calculated normal value]. In addition, transfer factor using the indicator gas CO (TL,CO) was unaltered in most patients [mean annual change -2.1% (5-95 PC -16.2 to +11.8) of predicted value]. However, there were significant decreases in the forced expiratory volume in 1 s (FEV1) before and after inhalation of 0.2 mg salbutamol [mean annual change -0.8% (5-95 PC -8.4 to +3.2) and -1.3% (5-95 PC -7.8 to +3.9) of the FVC measured, respectively]. In addition, there were significant increases in alveolar-arterial Po2 gradients (P(A-a),O2) at rest and after exercise [mean annual change +1.7 mmHg (5-95 PC -5.2 to +12.2) and +1.8 mmHg (5-95 PC -3.5 to 9.0), respectively]. Nevertheless, the amounts were small in view of the reliability of the methods applied and reflect, at least in part, the normal process of ageing. The annual change in FEV1/FVC was negatively correlated with FEV1/FVC at baseline (Rs = -0.46, P < 0.001). The annual change in TL,CO was also negatively correlated with TL,CO at baseline (Rs = -0.31, P = 0.028). No other risk factors for deterioration of lung volumes or gas exchange were found, including mean weekly MTX dose, age, gender, smoking, presence of rheumatoid factor and pulmonary function at baseline. We conclude that MTX has no major effect on pulmonary function in the majority of patients and that there is no evidence that patients with pre-existing pulmonary disease are at increased risk for further deterioration of lung function. | |
| 1604414 | [The treatment of rheumatoid arthritis with low dose pulse methotrexate--comparative study | 1992 Feb | Low dose pulse methotrexate (MTX, 5-7.5mg/week) was administered to fifty one patients with severe and active rheumatoid arthritis (RA) who did not respond to the various disease modifying antirheumatic drugs (DMARDs). The follow-up period ranged from 2 to 30 months. As to efficacy rate and probability of patients continuing therapy, the results of MTX were compared with those of the other DMARDs (131 cases of bucillamine (BU), 163 of D-penicillamine (DP), 98 of salazopyrin (SASP), 126 of auranofin (AF), 55 of lobenzarit (CCA)). The patients treated with MTX showed remarkable improvement within 1 or 2 months in Lansbury's index items, CRP, immunoglobulin levels and rheumatoid factor values. But OKT4/8 ratio remained unchanged throughout the study period. As to the adverse reactions due to MTX an elevation of serum transaminase occurred most frequently (41.2%). MTX treatment was, however, tolerable to the most cases with its transient discontinuance or its dose reduction. The efficacy rate of MTX (71.4%) was the best among above mentioned DMARDs at the end of 6 months treatment. After treatment of 24 months, the probability of still taking MTX (70.1%) proved to be about the same with that of DP and better than that of BU, SASP, AF and CCA. In conclusion low dose pulse MTX turned out to be effective in the treatment of severe and active rheumatoid arthritis. | |
| 8646436 | Effect of age on the efficacy and tolerance of methotrexate in rheumatoid arthritis. | 1996 May | The objective of this study was to assess the influence of age on the efficacy and toxicity of methotrexate in rheumatoid arthritis. Four hundred and sixty-nine patients were separated according to the age of onset of methotrexate treatment: before 65 yr (group 1, n = 416) and after 65 yr (group 2, n = 53). No difference was found in the evolution of clinical and biological parameters between the two groups. The number of patients in remission at the end of the study was equal. The frequency and type of side-effects were similar. No significant difference was found in the frequency and reasons for methotrexate withdrawal. We noted a trend towards lower therapeutic maintenance of methotrexate when prescribed after the age of 65 yr (P = 0.07, actuarial method). In conclusion, the age at initiation of methotrexate treatment probably did not influence its efficacy and toxicity in rheumatoid arthritis. | |
| 8527017 | Slow-acting antirheumatic drugs. Drug interactions of clinical significance. | 1995 Jul | The slow-acting antirheumatic drugs (SAARDs) are being used in an increasing proportion of patients with rheumatoid arthritis (RA). The potential toxicity of each drug is well recognised. Many patients with RA will be on other medications and the potential for adverse drug interactions with SAARDs is not so well publicised. There have, over the years, been numerous reports of possible drug interactions with SAARDs but few of these are clinically relevant. It is, however, vitally important that the physician is aware of a number of potentially life-threatening interactions, particularly those associated with methotrexate. The SAARDs are a very useful group of drugs for the treatment of RA and, by being aware of their potential toxicity and drug interactions, hopefully they can be used safely and effectively. | |
| 8833058 | Efficacy of triple DMARD therapy in patients with RA with suboptimal response to methotrex | 1996 Mar | Rheumatoid arthritis (RA) has a profound effect on patients, producing significant morbidity and in some cases mortality. Because of this, most rheumatologists are moving to disease modifying antirheumatic drug (DMARD) therapy earlier in the course of RA. Methotrexate (MTX) has become the initial DMARD of choice for most rheumatologists. Unfortunately, treatment of RA with a single DMARD, including MTX, often results in a suboptimal response. Therefore, most rheumatologists are now using combinations of DMARD to treat patients with RA who have had incomplete responses to single DMARD therapy. The Rheumatoid Arthritis Investigational Network (RAIN) reported the results of a double blind, controlled comparison of triple drug therapy (MTX-sulfasalazine-hydroxychloroquine) against MTX alone, and against the combination of hydroxychloroquine and sulfasalazine. Twenty-eight patients who had suboptimal responses to MTX or the combination of sulfasalazine and hydroxychloroquine were then treated with triple therapy in an open label study. Fourteen had previously failed MTX therapy, and 14 had previously failed combination therapy with sulfasalazine and hydroxychloroquine. Both groups had statistically significant improvements in sedimentation rates, morning stiffness, swollen joint scores, tender joint scores, patient global status assessment, and physician global status assessment. Statistical significance was reached for all these variables for patients in both groups, but improvement was greater for the patients in the sulfasalazine-hydroxychloroquine group. Patients with RA who have had suboptimal responses to MTX, or to the combination of sulfasalazine-hydroxychloroquine, show both statistical and clinically significant improvement in multiple clinical variables when treated with the combination of MTX 17.5 mg/week, sulfasalazine 500 mg bid, and hydroxychloroquine 200 mg bid. | |
| 8371203 | Renal effects of low dose methotrexate in rheumatoid arthritis. | 1993 Jul | OBJECTIVE: Methotrexate (MTX) treatment at high doses may cause renal failure. The effects of treatment with low MTX doses on kidney function are, however, unknown. The objective of our study was to investigate the effect of low MTX doses on kidney function. METHODS: The glomerular filtration rate was measured as the plasma clearance of 51Cr-EDTA and the clearance of 99mTc-dimercaptoacetyl-triglycine (correction of triglycerine) (99mTc-MAG3), a new renal tubular function agent, was used to measure tubular effects of MTX. RESULTS: Significant decrease of both 51Cr-EDTA clearance from 92 +/- 7 to 83 +/- 5 ml/min x 1.73 m2 (mean +/- SEM) and of the 99mTc-MAG3 clearance from 360 +/- 18 to 309 +/- 15 ml/min x 1.73 m2 (p < 0.05) was observed. CONCLUSION: Our results indicate that low dose MTX treatment (15 mg weekly) may significantly impair kidney function which has to be considered particularly in situations with combined treatment with other potentially nephrotoxic substances. | |
| 7944622 | Intraindividual variability of the bioavailability of low dose methotrexate after oral adm | 1994 Jul | OBJECTIVES: To analyse whether the intraindividual variability of the bioavailability of oral methotrexate in rheumatoid arthritis (RA) is as high as the interindividual variability and whether the bioavailability testing can be simplified. METHODS: Fifteen mg methotrexate was given orally after an overnight fast to 10 patients with RA on two occasions, one week (n = 4) or two years (n = 6) apart, respectively. Plasma samples were taken at specific time intervals and analysed by fluorescence polarisation immunoassay. The areas under the plasma concentration versus time curves from 0 to infinity (AUC) were calculated after fitting to a two-compartment extravascular model with lag time. RESULTS: The interindividual variability of the AUCs showed a more than five fold range from 77 to 471 min x mumol/l. In contrast, the intraindividual differences of AUCs between the two visits ranged from 3 to 100 min x mumol/l, reflecting a 3-30% change in nine of 10 patients. Close correlations were found between the AUCs and the plasma concentrations with a most pronounced correlation eight hours after methotrexate intake (r = 0.975; p < 0.001). CONCLUSIONS: The high interindividual variability of the AUCs was confirmed. Conversely, only a modest intraindividual variability was disclosed. Plasma sample analysis at a single time point four to eight hours after methotrexate application could simplify estimation of the bioavailability. | |
| 8670319 | Protein metabolism in rheumatoid arthritis and aging. Effects of muscle strength training | 1996 Jul | OBJECTIVE: To determine the effects of rheumatoid arthritis (RA) on whole-body protein metabolism. METHODS: We examined protein metabolism and its hormonal and cytokine mediators before and 12 weeks after progressive resistance muscle strength training in 8 healthy young (mean +/- SD age 25 +/- 2 years) and 8 healthy elderly (70 +/- 5 years) men and women, and in 8 adults with RA (42 +/- 13 years). An additional 6 healthy elderly subjects (69 +/- 3 years) served as a swimming-only control group. RESULTS: Subjects with RA had higher rates of protein breakdown than did young or elderly healthy subjects (79.9 +/- 17.2 versus 60.3 +/- 5.8 and 63.7 +/- 12.4 mumoles/gm total body potassium/hour, respectively, P < 0.05), while there was no effect of age per se. Patients treated with methotrexate had normal rates of protein breakdown (P < 0.01 versus RA without methotrexate; P not significant versus healthy young subjects). Increased protein catabolism in RA was no longer evident after strength training. In multiple regression analysis, levels of tumor necrosis factor alpha (TNF alpha) (r = 0.47, P = 0.01) and growth hormone (r = -0.51, P = 0.006) were associated with protein breakdown, and plasma glucagon levels were inversely correlated with protein synthesis (r = -0.45, P = 0.02). Growth hormone (r = -0.56, P = 0.002) and glucagon (r = 0.45, P = 0.04, levels were associated with protein oxidation. CONCLUSION: Adults with RA have increased whole-body protein breakdown, which correlates with growth hormone, glucagon, and TNF alpha production. | |
| 8124913 | The effect of methylprednisolone pulse therapy on methotrexate treatment of rheumatoid art | 1993 Dec | We randomly assigned 30 active rheumatoid arthritis (RA) patients who started oral methotrexate (MTX, 7.5 mg/week) treatment, into 3 groups. Group I received no additional corticosteroids; Group II was treated with 3 oral pulses of 100 mg prednisolone and Group III with 3 intravenous pulses of 1000 mg methylprednisolone (MP) on alternate days during the first week. Parameters of disease activity were measured at the start, after 10 days and at regular intervals up to 1 year. In Group I maximal improvement occurred after 18 weeks and in Group III after 6 weeks. This effect was sustained during the study. The initial effects in Group II were not as strong as in Group III and of shorter duration. No serious side effects were noticed. Our results suggest, that MP-pulse therapy seems to be useful in bridging the gap between the introduction of MTX and the response to this drug. Furthermore, we found that patients who were HLA-DR4-positive showed a better clinical response after 1 year than HLA-DR4-negative patients. | |
| 8587068 | What explains the variation among rheumatologists in their use of prednisone and second li | 1995 May | OBJECTIVE: To determine the extent to which characteristics of rheumatologists and their practices explain the variation in their use of prednisone and 2nd line agents for the treatment of rheumatoid arthritis (RA). METHODS: We used multiple logistic regression to examine the relationship between the use of prednisone, hydroxychloroquine, intramuscular gold, and methotrexate, and the following categories of rheumatologist characteristics: professional experience, primary payment method, practice setting, location of rheumatology training, and demographic characteristics. Our explanatory variables also included 12 patient characteristics and a random effect term. RESULTS: Much of the variation among rheumatologists in the use of these agents is explained by the rheumatologist characteristics. Depending on the agent, professional experience explained 15 to 54%, payment method 3 to 27%, practice setting 6 to 39%, training location 12 to 53%, and demographic characteristics 3 to 23% of the rheumatologist associated variation in use of each agent. CONCLUSION: There are identifiable characteristics of rheumatologists and their practices that strongly influence their treatment decisions for RA. These findings have important policy implications. | |
| 7858575 | [The risk/benefit ratio of low-dose cyclosporin in the treatment of severe rheumatoid arth | 1994 Dec | Although the efficacy of cyclosporine therapy in rheumatoid arthritis has been established, there have been no long term studies of the risk/benefit ratio of cyclosporine A in severe rheumatoid arthritis. A prospective, open-label one-year study included 106 patients (83 women and 23 men; mean age 53 years; mean disease duration, 11 years) with rheumatoid arthritis. Mean number of previous second-line treatments was four and 69% of patients had failed methotrexate therapy. The initial dosage of cyclosporine was 3 mg/kg/d and was increased if needed up to 5 mg/kg/d. The dosage was reduced in the event of serum creatinine elevation (by more than 30% versus baseline) or diastolic blood pressure elevation (above 95 mmHg). The statistical analysis was performed on an intention-to-treat basis. In the 45 patients who completed the one-year study period, the mean dosage was 3.6 +/- 1 mg after six months and 3.3 +/- 1 mg/kg/d after one year. Significant improvements were seen in all the clinical efficacy parameters. The mean reduction in corticosteroid dosage was 0.5 mg/d. The study drug was discontinued prematurely in 61 patients (36 because of adverse events and 21 because of inefficacy). Twelve of the 56 patients with serum creatinine level elevation on at least one occasion and seven of the 35 patients with diastolic blood pressure elevation were taken off the study drug. | |
| 8250989 | The effect of long-term methotrexate therapy on hepatic fibrosis in rheumatoid arthritis. | 1993 Dec | OBJECTIVE: To evaluate the progression of hepatic fibrosis in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). METHODS: Fifteen patients receiving MTX for RA were prospectively studied by electron microscopic analysis of biopsy specimens. RESULTS: Five of the 15 patients had evidence of increased hepatic collagen after 2 years of MTX therapy. CONCLUSION: Hepatic fibrosis may progress in a subgroup of RA patients treated with MTX. | |
| 7653488 | Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: a retrospect | 1995 Sep | PURPOSE: To evaluate the relationship between use of methotrexate in rheumatoid arthritis patients and development of hematologic malignancies. PATIENTS AND METHODS: We retrospectively analyzed all patients registered at the Mayo Clinic from 1976 through 1992 with rheumatoid arthritis (n = 16,263) cross-indexed with patients registered during the same period with a hematologic malignancy (n = 21,270). Adult patients were selected who had rheumatoid arthritis, were treated with a disease-modifying antirheumatic drug, and subsequently developed a hematologic malignancy. RESULTS: Thirty-nine patients met the selection criteria. Twelve of them had been given methotrexate. The characteristics of those who received methotrexate, including the type of hematologic malignancy, did not differ from those of patients who received other disease-modifying antirheumatic drugs. CONCLUSIONS: Hematologic malignancies are uncommon in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, including methotrexate. There does not appear to be a relationship between the peak or cumulative dose or the duration of methotrexate therapy and the subsequent development of hematologic malignancy. The histologic types of hematologic malignancy seen in the methotrexate-treated patients did not differ from those of patients treated with other disease-modifying antirheumatic drugs. | |
| 7837168 | Rheumatoid nodulosis of the meninges. | 1994 Oct | Rheumatoid nodulosis of the brain and leptomeninges has been reported only rarely, usually in patients with severe rheumatoid arthritis (RA). We describe the occurrence of leptomeningeal rheumatoid nodulosis occurring in a patient with nondeforming RA occurring in the setting of methotrexate therapy. |