Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8833059 | Combination therapy with cyclosporine in rheumatoid arthritis. | 1996 Mar | The role of combination therapy in rheumatoid arthritis is increasing with the recent development of various new treatment modalities. While past combinations of slow acting antirheumatic drugs have resulted in either excessive side effects or lack of efficacy over single agent therapy, recent combinations appear more promising. Recently, the combination of cyclosporine and methotrexate (MTX) was shown to be more efficacious than MTX alone. Improved methodology and a better understanding of the mechanisms of action of these newer agents is responsible for these exciting results. | |
| 8846540 | Osteoporosis in rheumatoid arthritis. | 1995 Sep | OBJECTIVE: To answer and comment on a number of controversial issues in relation to osteoporosis and rheumatoid arthritis (RA), including: Is osteoporosis an extra-articular manifestation of rheumatoid arthritis? Does periarticular osteoporosis reflect disease activity in early arthritis? Is there a threshold for corticosteroid-induced osteoporosis? Can anti-resorbing drugs prevent rheumatoid arthritis progression? Are stress fractures rare in rheumatoid arthritis Is methotrexate toxic for bone? METHODS: Confrontation of current literature and our own experience in order to formulate a general opinion. RESULTS AND CONCLUSIONS: Because most studies agree that osteoporosis in postmenopausal women and in men with RA is more evident at the hip and radius than at the spine, and that the most important determinants of bone loss are disability, local disease activity and cumulative corticosteroid dose, osteoporosis is not a common systemic extra-articular manifestation of RA. In early arthritis, periarticular osteoporosis does indeed reflect disease activity because it is closely related to the acute phase reactants, but once periarticular osteoporosis is established it is no longer a marker of disease activity. The threshold does for corticosteroid-induced osteoporotic fractures is the cumulative rather than the actual dose. Statements based on quantitative computed tomography concerning the acute effects (and their reversal) of corticosteroids on bone have to be interpreted with care because of important body composition changes, in particular in bone marrow fat, during corticosteroid treatment. At present there is no evidence that anti-resorbing drugs can change the progress of RA erosions, probably because erosions are the result of non-osteoclast mediated mechanisms. Stress fractures in RA are underdiagnosed and are often confused with synovitis, and therefore it is likely that they are more frequent than commonly thought, in particular at the lower limbs. Methotrexate osteopathy is known in oncological practice. Whether low dose methotrexate is toxic for bone is not clear, but a number of clinical observations suggest that the occurrence of spontaneous fractures and lower extremity pain is more frequent in methotrexate treated patients than expected. Prospective studies are necessary to confirm these impressions. | |
| 8278815 | Inverting the therapeutic pyramid: observations and recommendations on new directions in r | 1993 Oct | In evaluating current therapy for rheumatoid arthritis (RA), it is increasingly being recognized that sequential single-drug treatment, as exemplified by the traditional therapeutic pyramid, is often too little, too late, and ineffective in preventing disease progression or joint damage in patients with "at-risk," aggressive synovitis or what might be called type 2 RA. Designation of drugs as either antiinflammatory or disease-modifying is not supported by the author's experience. Evidence exists that prevention of joint damage correlates best with control of clinical and laboratory measures of inflammation, regardless of the medication used. The earlier and more effective the control of the inflammation, the better the patient response. Until a major breakthrough occurs, the author recommends that patients with aggressive RA be treated with a combination of fast-acting and slow-acting medications to achieve early control and then "bridge down" to a simplified maintenance program. Retrospective observation by the author of 54 patients with early, intermediate, and late disease treated with combinations of prednisone, methotrexate, auranofin, hydroxychloroquine, and azathioprine showed maximum response in patients with disease duration of less than 2 years, minimal toxicity, and lack of erosions in patients with control of inflammation. Twelve patients with inflammation not initially suppressed by prednisone and methotrexate had improved control with additional drugs in combination, including auranofin, hydroxychloroquine, and azathioprine. After inflammation was controlled, reduction of prednisone and methotrexate doses was possible in 60% of patients, primarily those with early disease.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 8523336 | Combination drug therapy of seropositive rheumatoid arthritis. | 1995 Sep | OBJECTIVE: To determine the longterm morbidity and mortality in a cohort of 169 patients with seropositive rheumatoid arthritis (RA) treated by a single rheumatologist with remittive agents used in combination. The effectiveness of a regimen combining pulse oral methotrexate, azathioprine and an antimalarial drug (MAH) was examined in detail. METHODS: All outpatient visits by patients followed for at least one year and up to 18 years (mean 7 years) were abstracted. Remittive antirheumatic drugs were used in combination to achieve progressive improvement. Univariate and multivariate analyses of the differences between first and last visit results in 9 process or outcome variables were calculated for the entire cohort, for those patients receiving or not receiving MAH at last visit, and for those patients taking methotrexate but not in combination with both azathioprine and an antimalarial. The numbers of patients in remission (Lansbury articular index zero), and near remission (articular index < 6) were determined for each of these groups. A survival curve was calculated. RESULTS: The entire patient cohort showed improvement in every variable except hemoglobin at the time of the last visit (p < 0.0004). On multivariate analysis MAH patients were improved only in American Rheumatism Association functional class compared to the other groups (p < 0.0001). Remission and near remission rates overall were 43 and 61%; for MAH patients 45 and 69% (p = n.s.). Survival was no different from that of the general population. Herpes zoster (17 patients) and second attacks of varicella (2 patients) were the most striking side effects. Prednisone use was reduced from 34 to 19% of patients and the mean daily dose was lowered from 9.3 to 5.9 mg. CONCLUSION: Combination therapy with multiple antirheumatic agents successfully controlled joint inflammation in 167 of 169 patients with seropositive RA; complete remission was achieved in 43% of patients. Survival of this patient cohort did not differ from that of the general population. | |
| 8434456 | Liver cirrhosis in rheumatoid arthritis patients treated with long-term methotrexate. | 1993 Feb | We undertook a retrospective review of all the liver biopsies done by us between 1985 and 1990 for the purpose of monitoring methotrexate (MTX)-induced hepatotoxicity in rheumatoid arthritis (RA) patients. A total of 29 biopsies were done in 25 patients. The mean total cumulative dose of MTX was 1585 +/- 348 (SD) mg. Average duration of MTX therapy was 31 +/- 9.8 mo (SD). Liver biopsy after accumulating 900 mg and 1200 mg MTX, respectively, in 2 obese diabetic patients showed evidence of cirrhosis. Obese diabetics may represent a subgroup of RA patients at risk for developing MTX-induced hepatotoxicity. | |
| 7561491 | Inner ear involvement in rheumatoid arthritis: a prospective clinical study. | 1995 Aug | Sensorineural hearing loss in rheumatoid arthritis (RA) has been reported to be the result of the extra-articular manifestation of the disease (rheumatoid nodular vasculitis) or due to drug ototoxicity. In an attempt to investigate the presence of sensorineural hearing loss and the possible causes for it we investigated prospectively 45 RA patients (42 female; three male) with a mean age of 52.5 +/- 10.7 years and a mean disease duration of 8.5 +/- 7.3 years. All patients underwent a complete physical examination and audiological evaluation which included pure tone audiometry and impedance audiometry (tympanogram, static compliance, acoustic reflex, reflex decay, acoustic reflex latency test. We found a sensorineural hearing loss > 20 dB HL in 44.4 per cent (40/90) ears. In all cases the site of hearing loss was the cochlea and in most of them it was bilateral and symmetric (16 patients out of 45 had bilateral sensorineural hearing loss i.e. 35.5 per cent. There was no correlation between sensorineural hearing loss and age, sex, disease duration, articular and extra-articular manifestations and the presence of autoantibodies in our patients. In addition, no correlation was found between sensorineural hearing loss and drug therapy for one at least of the following drugs: NSAIDs, D-penicillamine, plaquenil and methotrexate. We noticed a prologation of acoustic reflex latency in five patients (10 per cent) which was found to be correlated with the temporomandibular joint involvement and the presence of rheumatoid factor (RF). We conclude that inner ear involvement in RA is expressed by: (1) mild symmetric, bilateral sensorineural hearing loss of cochlear type in 35.5 per cent of patients; (2) normal acoustic reflex thresholds; (3) nondecay; and (4) prologation of acoustic reflex latency which appeared in a small number of patients (10 per cent). | |
| 7871907 | [Incidence of acral nodulosis with long-term methotrexate therapy in patients with inflamm | 1994 Nov | The significance of acral nodulosis under methotrexate therapy is still controversial. Among patients with rheumatoid arthritis and methotrexate therapy this manifestation could be observed in 8/163 (5%). All cases were seropositive and already treated with other LAAD. Patients with other inflammatory rheumatic diseases under methotrexate therapy (n = 83) did not develop this nodulosis. The acral nodulosis is interpreted as a typical side-effect of methotrexate only in patients with rheumatoid arthritis. Histopathologically, these nodules do not differ from the typical rheumatoid nodule. | |
| 8587069 | Use of second line drugs for the treatment of rheumatoid arthritis in Edmonton, Alberta. P | 1995 May | OBJECTIVE: Our purpose was to compare the patterns of prescription of 2nd line drugs for the treatment of rheumatoid arthritis (RA) among rheumatologists in Edmonton, Alberta, and to examine the longterm effectiveness of these drugs. METHODS: A 1985 inception cohort of 128 patients with RA was assessed between 1991 and 1992, using measures of disease activity, radiological scores and physical functional status. Use of different therapies was retrieved from the medical charts. RESULTS: All patients had seen a rheumatologist at any time between January, 1985 and December, 1991, 88% within the first 3 years of disease. Most (85%) had received at least one 2nd line drug, the majority within the first 2 years. Overall, gold salts were the most frequently prescribed drugs. Patterns of prescription varied among different rheumatologists; some drugs were never prescribed by some and very often by others (e.g., auranofin). Terminations because of toxicity and lack of efficacy were high. Methotrexate (MTX) had the lowest termination rate and sulfasalazine the highest, mostly due to lack of efficacy. CONCLUSION: In this cohort, patients were treated early in the course of RA. Patterns of prescription of 2nd line drugs varied among rheumatologists. Termination rates were highest for sulfasalazine and lowest for MTX. | |
| 1445448 | Efficacy and safety of 10-deazaaminopterin in the treatment of rheumatoid arthritis. A one | 1992 Nov | OBJECTIVE: To determine the long-term safety and efficacy of 10-deazaaminopterin (10-DAM) in the treatment of rheumatoid arthritis (RA). METHODS: A 1-year continuation of an initial 15-week randomized, double-blind clinical trial of 10-DAM and methotrexate (MTX). RESULTS: 10-DAM (n = 10) and MTX (n = 8) had comparable safety and efficacy profiles. One 10-DAM-treated and 2 MTX-treated patients experienced transient side effects; 1 MTX-treated patient experienced recurrent nausea and discontinued MTX. CONCLUSION: 10-DAM appears to be as beneficial and as safe as MTX for the treatment of RA. | |
| 8849352 | Comparison of azathioprine, methotrexate, and the combination of the two in the treatment | 1995 Dec | OBJECTIVE: To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA) in a double-blind, prospective, multicenter, controlled trial. METHODS: Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5mg MTX/week plus 50 mg AZA/day-7.5 mg MTX/week plus 100 mg AZA/day), with opportunity to increase the dosage at 6-week intervals. The patients were evaluated for significant clinical and laboratory improvement and assessed for radiologic progression at 48 weeks. RESULTS: One hundred ten patients remained on the initial, randomly assigned therapeutic regimen. The percentage of patients who were responders, defined as those who had 30% or greater improvement in at least 3 of 4 variables, was 38% for the combination treatment, 26% for AZA, and 45% for MTX (P = 0.06). A trend toward decreased radiologic progression was seen in the MTX-treated patients. Termination of treatment due to adverse experience occurred more frequently with combination and AZA treatments than with MTX treatment. Lack of effectiveness, adverse gastrointestinal effects, and liver enzyme elevation were the most frequent causes of treatment discontinuation. CONCLUSION: This study establishes that the combination of MTX and AZA in the dosages utilized is not associated with more toxicity than treatment with single agents; however, enhanced efficacy is also not seen. There is a trend toward decreased radiologic progression in patients treated with MTX. | |
| 8573295 | Management of adverse effects of disease-modifying antirheumatic drugs. | 1995 Oct | Therapy with disease modifying antirheumatic agents (DMARDs) is often complicated by the occurrence of adverse effects. Although risk factors for several DMARDs have been reported, the prediction of adverse drug reactions is not yet possible. Therefore regular monitoring remains mandatory. Monitoring for adverse effects to DMARDs usually includes one or more of the following: blood count, liver, kidney, urine or ophthalmologic tests. Since most adverse reactions occur during the first few months of treatment, monitoring should be more intense and frequent in this initial phase. Some adverse effects are dose-dependent, and therefore dosage reduction may help alleviate these. Others are idiosyncratic, and often necessitate drug withdrawal. Except for (hydroxy)chloroquine-induced retinopathy and methotrexate-induced liver cirrhosis, most adverse reactions to DMARDs are fortunately reversible. | |
| 8485020 | The pharmacokinetics of methotrexate and its 7-hydroxy metabolite in patients with rheumat | 1993 Apr | 1. The pharmacokinetics of MTX and its 7-hydroxy metabolite (7-OHMTX) were investigated in nine patients with rheumatoid arthritis (RA). Each patient received 15 mg MTX i.v., i.m. and p.o. after an overnight fast in a randomized cross-over design. The plasma concentrations of MTX and 7-OHMTX were measured over 7 days and their urinary excretion over 24 h. 2. Plasma concentrations of MTX were described by a triexponential function after i.v. administration, a triexponential function with zero or first order absorption after oral administration, and a biexponential function with zero of first order absorption after i.m. injection. Plasma concentrations of 7-OHMTX were described by a biexponential function after all three routes of administration. The median terminal elimination half-lives of MTX and 7-OHMTX were 55 h and 116 h, respectively. The area under the plasma concentration-time curve (AUC (0,170 h)) of MTX did not differ between i.m. and oral administration indicating similar bioavailability after these routes of administration. The AUC (0,170 h) values of 7-OHMTX after i.v., oral and i.m. administration were similar. Over 80% of MTX was excreted in urine as intact drug and about 3% was excreted as 7-OHMTX during 24 h after drug administration. 3. Plasma concentrations of MTX and 7-OHMTX were measurable at the end of the dose interval in most of the patients and may help to identify non-responders or patients with increased risk of side-effects. | |
| 8630111 | Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifyi | 1996 Apr | OBJECTIVE: Therapeutic strategies for rheumatoid arthritis (RA) have been evolving from the traditional "pyramid" approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs (DMARDs), in the hope of improving long-term health outcomes. However, few data to have been presented to document the effects of this approach. We sought to directly assess associations between consistent DMARD use and long-term functional outcomes. METHODS: We studied 2,888 RA patients who were followed up prospectively for up to 20 years (average 9 years) at 8 databank centers. The independent variable was the proportion of patient encounters that resulted in treatment with > or = 1 DMARD (hydroxychloroquine, sulfasalazine, auranofin, intramuscular gold, D-penicillamine, methotrexate, and/or azathioprine). The dependent variable was each patient's last recorded Disability Index value from the Health Assessment Questionnaire (HAQ). RESULTS: Increased DMARD use was strongly associated with better long-term Disability Index values (P < 0.0001). The association was strengthened when restricted to more seriously affected (rheumatoid factor (RF)-positive) patients. The magnitude of the effect, unadjusted, was a difference of 0.53 HAQ Disability units (scale 0-3) between 100% DMARD use and 0%. Correlation coefficients ranged up to 0.26. Effects were similar for all disease duration periods (0-4, 5-9, 10-14, 15-19, and 20+ years). "Control" correlations, with variables computed to represent the proportion of time in which patients were taking either nonsteroidal anti-inflammatory drugs or prednisone, failed to show positive associations. A multiple linear regression model, which controlled for age, disease duration, sex, RF positivity, proportion of visits under a prednisone regimen, and initial disability level, included the proportion of time in which patients were taking DMARDs (P < 0.0001), with a model R2 of 0.54. These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDS more frequently, and despite absence of data on drug use early in the disease course of many patients. Thus, these results, which suggest up to a 30 percent reduction in long term disability with consistent DMARD use, are most likely conservative. CONCLUSION: An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data. | |
| 8619103 | The changing face of therapy for rheumatoid arthritis. | 1995 Aug | This article reviews past and present prescribing patterns for patients with rheumatoid arthritis and reveals some striking differences over time. For many practitioners, methotrexate has become the centerpiece around which other therapies are built; however, we are still learning a great deal about this drug. In this article, some recent advances are described. The prospects for further therapeutic development are discussed, with a focus on the present state-of-the-art combination chemotherapeutic regimens. Consideration is given to ways in which new approaches might facilitate clinical research in this severely underfunded area. | |
| 7821884 | [Does methotrexate induce "rheumatoid nodules"? Case report and discussion of the literatu | 1994 Nov 20 | A 58-year-old woman with chronic polyarthritis rapidly developed a large number of rheumatic nodules under treatment with methotrexate. A comparison with other cases reported to date showed that the sudden onset of such nodules after initiation of treatment, and their disappearance again after discontinuation of the drug make the causal relationship highly likely. Although the predominantly anti-inflammatory actions of methotrexate control the chronic polyarthritis in almost all cases so far reported, they are unable to prevent the primarily immunological tissue necrosis (rheumatic nodules) and may even promote their development through the liberation of adenosine. Only in very rare cases does the severity or localisation of the nodules--e.g. vasculitis, pulmonary or cardial manifestation--necessitate the discontinuation of methotrexate. | |
| 8778986 | Cost evaluation of novel therapeutics in rheumatoid arthritis (CENTRA): a decision analysi | 1996 Apr | This study was performed to evaluate the potential costs of a hypothetical novel biological agent (BIO) as a therapy for rheumatoid arthritis (RA), compared with oral methotrexate (MTX) and intramuscular gold (IMG). A decision analysis model was used to compare the total costs of treating a cohort of 10,000 RA patients with each agent for 6 months. Total costs included direct costs and indirect costs. Baseline estimates were subjected to sensitivity analysis. Total costs per person were: MTX, $5,430; IMG, $6,725; BIO, $9,411. In sensitivity analysis, the primary cost drivers for MTX and IMG were the indirect costs of RA and monitoring costs. In contrast, total costs of the BIO were driven predominantly by medication costs. Sensitivity analysis showed, even when efficacy and safety were optimized, costs for the BIO still substantially exceeded those of MTX and IMG. Medication costs will be an important consideration in the development of novel BIOs for RA. | |
| 8866922 | Lack of interaction between flucloxacillin and methotrexate in patients with rheumatoid ar | 1996 Mar | 1. The aim of the study was to examine the potential pharmacokinetic interaction between methotrexate and flucloxacillin. 2. Ten rheumatoid arthritis patients participated in the interaction study. Subjects were allocated to either methotrexate alone (5-15 mg per week) or methotrexate plus flucloxacillin (500 mg four times a day 48 h prior to sampling) in a random order. 3. There was a statistically, but not clinically, significant decrease in methotrexate AUC (1307 +/- 389 vs 1212 +/- 394 micrograms l-1 h) in the presence of flucloxacillin. Cmax and tmax parameters for methotrexate were not significantly altered in the presence of flucloxacillin. 4. Data from an additional 10 rheumatoid arthritis patients, starting on methotrexate, were added to the data from the placebo arm of the interaction study and a model dependent pharmacokinetic analysis was performed. The plasma concentration profiles were best described by a two-compartment model with a mean clearance of 11.9 (+/- 1.7) l h-1 and an initial volume of distribution of 31.2 (+/- 2.6) l. The pronounced intersubject variability in the pharmacokinetic parameters was not related to any of the available covariate information. 5. Our findings suggest that no important clinical interaction occurs between flucloxacillin and methotrexate in patients with rheumatoid arthritis. | |
| 8571264 | [The effect of basic therapy on the morphological picture of the rectal mucosa in patients | 1995 | 140 rectal mucosa biopsies were obtained from 86 patients with rheumatoid arthritis (RA), from 54 RA patients prior to or after a year basic therapy with either methotrexate or sulfa drug (sulfasalazine or salazopyridazine). 80% of the examinees exhibited large macrophages, lymphoid follicules, IgM- and IgG-containing cells. The knowledge of the initial morphologic changes in the rectal mucosa from RA patients helps predict efficacy of methotrexate or sulfonic drug treatment. Rectoromanoscopy with biopsy proved important diagnostic tool in RA capable of differentiating the disease variants, prompting valid therapeutic approach with control of the treatment results. | |
| 7699678 | Pharmacokinetics and renal function in patients with rheumatoid arthritis receiving a stan | 1995 Jan | OBJECTIVE: To determine the pharmacokinetics of a standard oral dose of 7.5 mg in a cohort of patients beginning methotrexate (MTX) and continuing the drug over 24 months. METHODS: Twenty-one patients underwent pharmacokinetic testing after receiving a dose of 7.5 mg of oral MTX and concomitant nonsteroidal antiinflammatory drug (NSAID) therapy. Studies were performed at the time of MTX initiation, and after 6 and 24 months of therapy. RESULTS: No significant differences with time were observed in area under the serum concentration versus time curve (AUC), maximal MTX concentration achieved postdosing (Cmax) or time to maximal MTX concentration (Tmax). Renal clearance of MTX at 6 months decreased by a mean (+/- SD) of 23.8 (40.3) cc/min (p = 0.014). Creatinine clearance decreased by 8.6 cc/min (17.2) (p = 0.033) at 6 months. CONCLUSION: No differences in AUC, Tmax, or Cmax were observed over a 2 year period in patients with rheumatoid arthritis on a standard 7.5 mg dose of MTX. Renal clearance and creatinine clearance both decreased significantly after 6 months of treatment. This effect may be clinically relevant in certain individuals as MTX is renally excreted. | |
| 8367633 | [Treatment of rheumatoid arthritis: current and future]. | 1993 Jun | Rheumatoid arthritis (RA) is a chronic articular inflammatory disease of unknown aetiology. The therapeutic approach can be achieved at different levels: 1) symptomatic treatment with nonsteroidal anti-inflammatory drugs which can relieve articular pain and stiffness, 2) second-line drugs (or DMARD, for Disease Modifying Anti-Rheumatic Drug) selected for their capacity to slow the rheumatoid process. During this last decade, sulfasalazine and methotrexate became an alternative choice to the "classical" slow-acting antirheumatic drugs such as gold, D-penicillamine or antimalarials. The extensive progress in basic immunology and especially in the immunopathology of RA has allowed the elaboration of a new approach to immunotherapy, aimed at molecular targets on cells from the "specific immunity" system or against mediators of the inflammatory process, such as the cytokines. |