Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 10827366 | [Treatment of rheumatoid polyarthritis with methotrexate in Dakar: efficacy, tolerance and | 2000 Jan | Methotrexate (MTX), which has been used for years in cancer treatment, is now being proposed as a first-line treatment for rheumatoid arthritis (RA), despite its potential side effects. The aim of this study was to investigate the short-term efficacy, safety and relative cost of low-dose MTX for the treatment of RA. We carried out an open, nonrandomized trial in which patients received a 7 mg injection of MTX once per week, with clinical and biological follow up. A single physician performed the weekly assessments, which involved evaluation of the duration of morning stiffness, the number of night awakenings, the number of painful and swollen joints and Ritchie's index. Blood cell count and erythrocyte sedimentation rate were determined monthly. Twelve RA patients were enrolled in the trial, over a mean treatment period of 356 +/- 175 days. A significant improvement was observed in all variables except the number of swollen joints. Ritchie's index decreased from a mean of 31.8 +/- 11.85 to 6.5 +/- 8.98 (p<1.6 x 10- 4). Minor adverse reactions were observed but none indicated treatment withdrawal: 6 cases of nausea, 2 of a moderate increase in transaminase activity, 1 of bronchitis, in which the responsibility of MTX was not definitely established and 3 cases in which hemoglobin levels decreased. The monthly cost of the treatment, including the drug itself and laboratory tests, is lower than that of gold salt injection. Three issues of key importance in our region were investigated in this study: 1) the possible desire to become pregnant of female patients undergoing MTX treatment. In addition, some of the young and unmarried patients did not understand or appreciate the contraceptive effects of the treatment; 2) poor compliance with the treatment due to limited financial resources. Many patients did not regularly attend for their follow-up appointments and many stopped taking the medication. One third of the patients were lost to follow-up during this study; 3) the prevalence of chronic hepatitis, which may limit the use of MTX in our region. Serological tests should be performed before the treatment is started and a liver biopsy is recommended for patients with chronic hepatitis B or C. | |
| 10328583 | Molecular and cellular effects of methotrexate. | 1999 May | In 1998, knowledge about the mechanisms of action of methotrexate (MTX) in immunoinflammatory disorders further increased. The most interesting results to date came from studies showing that most of the anti-inflammatory actions of MTX are mediated by adenosine, which may account for the profound effects of MTX on cytokines, cytokine inhibitors, and cell differentiation. Finally, potential novel pharmacologic strategies are discussed based on actual knowledge about the molecular and cellular actions of MTX. | |
| 10782805 | Chimeric anti-tumor necrosis factor-alpha monoclonal antibody treatment of patients with r | 2000 Apr | OBJECTIVE: To evaluate the safety and efficacy of single and multiple doses of a chimeric anti-TNF-alpha monoclonal antibody (infliximab) in patients with rheumatoid arthritis (RA) who had active disease despite therapy with methotrexate (MTX). METHODS: Twenty-eight patients with active RA despite receiving therapy with 10 mg/week of MTX were randomized to receive a single, blinded infusion of either placebo or 5, 10, or 20 mg/kg infliximab. Twenty-three patients who completed the blinded study entered an open, multiple dose extension study in which they received up to 3 additional infusions of 10 mg/kg infliximab at Weeks 12, 20, and 28. Safety, efficacy, and pharmacokinetics were evaluated during the blinded and open trial. RESULTS: There were no serious infusion related reactions. In the blinded phase, 17 (81.0%) of 21 patients receiving infliximab achieved an American College of Rheumatology (ACR) 20% response at some point during the 12 weeks of followup compared to one (14.3%) of 7 patients receiving placebo (p = 0.003). Clinical improvement was evident by the first week and was sustained through Week 12. For the 19 patients who received infliximab during the blinded part of the trial and continued into the open label trial, 53% maintained an ACR 20% response with multiple infusions of 10 mg/kg infliximab through Week 40. Three patients withdrew from the trial during the open continuation phase because of adverse events: cellulitis, infusion related dizziness and headache, and vasculitic rash. Infliximab in doses of 5 to 20 mg/kg had a mean terminal half-life ranging from 9 to 12 days and was detectable in sera from most patients 8 to 12 weeks after dosing. CONCLUSION: Infliximab is generally well tolerated during 40 weeks of therapy. A single infusion of 5 to 20 mg/kg infliximab significantly decreases the signs and symptoms of RA compared to placebo in patients with active disease receiving MTX. Multiple doses of infliximab produce sustained clinical benefit for up to 40 weeks. | |
| 9608316 | Disease-modifying antirheumatic drugs. | 1998 May | Disease-modifying antirheumatic drug (DMARD) therapy is now clearly accepted as the primary treatment for rheumatoid arthritis, with an increasing emphasis on use of combination therapy. Data on combination therapy have highlighted the difficulties in performing these studies and the large number of patients required to produce meaningful results. Combination studies have focused on use of rapidly decreasing high-dose steroids as a part of the combination and emphasize the importance of using patients with early rheumatoid arthritis. Even with relatively aggressive use of DMARDs, the majority of patients develop erosions. Adverse reactions to DMARDs continue to concern clinicians, although evaluation of the frequency of these events has led to a reappraisal of previously accepted monitoring strategies in some cases. For example, it may not be cost-effective to subject patients on antimalarials to regular review by an ophthalmologist because of the low frequency of serious eye defects. Studies have also identified risk factors for the development of pulmonary toxicity in association with methotrexate. That DMARDs are effective in treating rheumatoid arthritis is beyond question-just how effective they are and what combinations of DMARDs will show improved efficacy will provide data for the next annual review. | |
| 10534552 | Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid a | 1999 Oct | OBJECTIVE: The mechanism of anti-inflammatory effects of methotrexate (MTX) at low dose may relate to a decrease in availability of the purine precursor or it may depend on accumulation of 5-aminoimidazole-4-carboxamide (AICAR) and the anti-inflammatory nucleoside adenosine. The aim of this study was to evaluate the possible mechanism of action by analysis of changes in blood concentrations of purine and pyrimidine metabolites during MTX treatment. METHODS: Venous blood samples were collected from rheumatoid arthritis patients before and at different times for up to 7 days after the start of MTX treatment. Whole blood concentrations of adenosine, uridine, hypoxanthine, uric acid and erythrocyte nucleotides were measured by HPLC. RESULTS: The initial blood adenosine concentration was 0.073 +/- 0.013 microM and no differences were observed during MTX treatment. However, a decrease in uric acid concentration was observed from 205.5+/-13.5 to 160. 9+/-13.5 microM (P<0.05) within 24 h after MTX administration. The hypoxanthine concentration decreased in parallel with uric acid, while the uridine concentration decreased 48 h after MTX administration. No accumulation of AICAR-triphosphate (ZTP) was observed in the erythrocytes. CONCLUSIONS: MTX decreases circulating purine and pyrimidine concentrations, and their availability for DNA and RNA synthesis, which may affect immune cell proliferation and protein (cytokine) expression. The absence of adenosine concentration changes and lack of ZTP formation is evidence against an AICAR/adenosine mechanism, although localized adenosine concentration changes cannot be excluded. | |
| 11273473 | Doxycycline in the treatment of rheumatoid arthritis--a pilot study. | 2000 Aug | OBJECTIVE: To assess the efficacy and safety of doxycycline as a disease modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA) and compare it with methotrexate, a standard DMARD. MATERIAL AND METHODS: A single (assessor) blind prospective study with 15 patients of RA randomized to doxycycline and 14 to methotrexate. Baseline disease characteristics were similar in both groups. RESULTS: All disease activity measures studied viz. tender and swollen joint counts, physician and patient global assessment, visual analogue pain scale, health assessment questionnaire and ESR improved in both the treatment groups after six months of treatment. The difference between doxycycline and methotrexate was not statistically significant. No major side effects necessitating drug withdrawal were reported from either group. The side effects were few and mostly gastrointestinal. CONCLUSION: Doxycycline is a safe disease modifying drug in RA whose effect is sustained at six months. It compared favourably with methotrexate over a six month follow up. | |
| 10651393 | Leflunomide: a review of its use in active rheumatoid arthritis. | 1999 Dec | A77 1726, the active metabolite of leflunomide, is an immunomodulator which inhibits cell proliferation in activated lymphocytes in patients with active rheumatoid arthritis. Because A77 1726 has a long half-life (approximately 2 weeks), treatment with oral leflunomide is initiated with a loading dose of 100mg once daily for 3 days and continued with 20mg once daily. Results of large randomised, double-blind, multicentre trials of up to 24 months' duration have shown that leflunomide is significantly superior to placebo and at least as effective as sulfasalazine in improving primary outcome measures, such as tender joint counts, swollen joint counts and physicians' and patients' global assessment, in adult patients with active rheumatoid arthritis. Whereas improvement in all primary outcome measures with leflunomide was similar to or significantly less than that with methotrexate after 12 months, the efficacy of both agents was similar after 24 months. The therapeutic effect of leflunomide appears earlier (at 4 weeks) than that of sulfasalazine or methotrexate, and reduction from baseline values in functional disability was significantly greater with leflunomide than with sulfasalazine, methotrexate or placebo at end-point. Leflunomide was at least as effective as sulfasalazine or methotrexate in delaying the rate of radiological progression of disease. The most common adverse events reported in patients receiving leflunomide in randomised double-blind, placebo-controlled trials were diarrhoea (27%), respiratory infections (21%), nausea (13%), headache (13%), rash (12%), increased serum hepatic aminotransferases (10%), dyspepsia (10%) and alopecia (9%). Leflunomide was as well tolerated as sulfasalazine or methotrexate in clinical trials. Monitoring of serum hepatic enzyme levels is recommended in patients receiving leflunomide. The drug is not recommended in female patients who are or may become pregnant. Drug treatment should be discontinued, and hastened drug elimination procedure should be considered, in male patients wishing to father a child. 16 potential cases of pancytopenia and 9 cases of serious skin reactions have been associated with the use of leflunomide in 76,000 patients to date. CONCLUSIONS: Leflunomide is a disease-modifying antirheumatic drug which reduces the signs and symptoms of inflammatory arthritis and delays the radiological progression of disease in adult patients with active rheumatoid arthritis. The drug appears to be as effective and as well tolerated as sulfasalazine or methotrexate, and represents a suitable alternative to these agents in adult patients with active rheumatoid arthritis. Benefits with leflunomide are evident within 4 weeks and efficacy is maintained for durations of up to 24 months. | |
| 10852288 | Primary cutaneous B cell lymphoma during methotrexate therapy for rheumatoid arthritis. | 2000 Jun | A patient with rheumatoid arthritis developed a reversible, primary cutaneous, large B cell lymphoma during prolonged methotrexate (MTX) treatment. Regression of the skin lesions after discontinuation of the drug suggested a close relationship to MTX. Increased clinical awareness, discontinuation of MTX, and close observation are important in the initial management of this rare lymphoproliferative disorder. | |
| 11289656 | An investigation of cell proliferation and soluble mediators induced by interleukin 1beta | 2001 Feb | OBJECTIVES AND DESIGN: The difference in cell proliferation and release of soluble factors in response to interleukin 1beta (IL-1beta) in fibroblasts obtained from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) and from normal skin has been investigated. TREATMENT: The cells were treated with recombinant IL-1beta in the presence or absence of pharmacological agents for 24 h or 48 h. METHODS: Cell proliferation was examined by WST-1 assay, and the amounts of interleukin-6 (IL-6), interleukin-8 (IL-8), macrophage colony stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix metalloproteinase-1 (MMP-1), and prostaglandin E2 (PGE2) were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: IL-1beta dose-dependently enhanced the proliferation of all fibroblasts. The proliferative response to IL-1beta in RA synovial fibroblasts was greater than that in OA synovial and skin fibroblasts. However, there was no difference in spontaneous levels of soluble factors between OA and RA fibroblasts, though medium concentrations of IL-1beta-released VEGF, MMP-1, and PGE2, but not cytokines, in RA were slightly higher than those in OA. Ability to release soluble mediators was pronouncedly increased at 3 h to 9 h after stimulating fibroblasts with IL-1beta for 1 h. The proliferative response to IL-1beta in all fibroblasts was inhibited by dexamethasone and the NF-kappaB inhibitor hymenialdisine but not the cyclooxygenase 2 (COX-2) inhibitor NS-398. But PGE2 prevented proliferation of RA fibroblasts when added to medium up to 3 h after IL-1beta stimulation. Dexamethasone also inhibited the release of IL-6, IL-8, and PGE2 induced by IL-1beta in both OA and RA fibroblasts. NS-398 exhibited an inhibition of IL-1beta-induced IL-6 production as well as PGE2 production. Hymenialdisine inhibited IL-6 production and reduced IL-8 production dependent on synovial cell strains. Methotrexate had no effect on the response to IL-1beta in synovial fibroblasts. CONCLUSION: The present results indicate that the activation of NF-kappaB plays an important role in the proliferative response to IL-1beta in human fibroblasts, and suggest that PGE2 acts as a modulator of cell proliferation in inflamed synovial tissue. It appears that the ability to produce soluble factors in RA synovial fibroblasts is not intrinsic. However, the response to IL-1beta in RA cells seems to be greater than that in OA cells. | |
| 11043056 | [Leflunomide for active rheumatoid arthritis]. | 2000 Sep 25 | In 1999, leflunomide was introduced for the treatment of active rheumatoid arthritis. Leflunomide is a reversible inhibitor of "de novo" synthesis of pyrimidine, resulting in a restriction of lymphocyte proliferation. The pharmacodynamics are characterized by slow elimination. Leflunomide has shown an efficacy and a pattern of mild and serious side effects similar to methotrexate and sulphasalazine. Treatment is started with a loading dose of 100 mg orally for three days followed by 20 (10) mg daily. Regular haematological measurements, determination of serum chemistry and blood pressure should be performed every second week the first six months, subsequently every sixth week. If the treatment is to be terminated abruptly, a drug elimination procedure must be performed. Leflunomide will find its place in the treatment of rheumatoid arthritis. Leflunomide should follow an unsuccessful treatment attempt with methotrexate or sulphasalazine. | |
| 10529125 | The safety and efficacy of cyclosporine (Neoral) in rheumatoid arthritis. | 1999 Oct | OBJECTIVE: To assess the safety and efficacy of cyclosporine (Neoral), its steroid sparing effect, and its usefulness in combination therapy with methotrexate (MTX) in the treatment of refractory rheumatoid arthritis (RA). METHODS: All patients given cyclosporine for refractory RA over a 21 month period were included in an open, prospective study. Patients were reviewed initially fortnightly then monthly with clinical evaluation and serum creatinine. There were no restrictions on the use of other disease modifying agents, nonsteroidal antiinflammatory drugs, or corticosteroids. RESULTS: Forty-six patients with severe RA were included in the study, 33 (72%) female and 13 (28%) male, with a mean age of 54.8 years (range 20-74). At the completion of the study 30 (65%) were still taking cyclosporine at a mean dose of 2.94 mg/kg/day for a mean duration of 10.5 months. Thirteen patients discontinued cyclosporine due to side effects, most commonly gastrointestinal, and 3 due to inefficacy. Thirty-seven of the 46 patients were taking prednisolone at the start of the study at a mean dose of 10.36 mg/day, which decreased to 7.068 mg/day at the end of the study (p < 0.001). Thirty patients used cyclosporine in combination with MTX. The mean dose of MTX decreased from 15.08 to 13.67 mg/wk (p = 0.02). The mean serum creatinine increased by 13% from 74 to 83.7 micromol/l. Patients who continued therapy had a shorter duration of disease, with a mean of 9.93 years compared to 15.73 years in those who stopped therapy (p = 0.004). CONCLUSION: Cyclosporine (Neoral) was a safe and effective therapy in this population of patients with RA refractory to standard therapy. We observed a significant steroid sparing effect and have shown that combination therapy with MTX does not increase side effects and allows for a decrease in MTX dose. Renal function is not adversely affected if guidelines are followed. | |
| 11085806 | Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial | 2000 Nov | OBJECTIVE: To examine whether different combinations of disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX), salazosulphapyridine (SASP) and dexamethasone (DEX; a steroid), act by inhibiting the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cultured synoviocytes, causing a decrease in their serum concentrations in patients with rheumatoid arthritis (RA). METHODS: The VEGF and bFGF concentrations in cultured synoviocytes and peripheral blood from patients with RA were measured by enzyme-linked immunosorbent assay and their serum concentrations were measured at two time points. RESULTS: BUC and GST inhibited VEGF production even when given alone, and a combination of BUC, GST and MTX with DEX also inhibited VEGF production. None of the DMARDs or DEX inhibited bFGF production when given alone, but a combination of SASP and GST inhibited the production of bFGF in cultured synoviocytes. Serum VEGF concentrations were significantly decreased 6 months after the commencement of medication compared with their concentrations before medication. CONCLUSION: Our results show that the effects of a combination of DEX with any two of BUC, GST, SASP and MTX on the production of VEGF and bFGF in cultured synoviocytes and on the serum concentrations of VEGF in patients with RA may be based on synergistic or additive effects of the drugs. | |
| 9058671 | Herpes zoster encephalomyelitis associated with low dose methotrexate for rheumatoid arthr | 1997 Mar | We describe herpes zoster encephalomyelitis occurring 9 days after the onset of cutaneous zoster in an elderly patient taking low dose weekly methotrexate without concomitant prednisolone. | |
| 11718154 | Leflunomide and rheumatoid arthritis: new preparation. Neither the safest nor the most eff | 2001 Apr | (1) There is no consensus on the reference disease-modifying antirheumatic drug. Three drugs are often prescribed as a first line option: methotrexate for its efficacy, and sulfasalazine and hydroxychloroquine for their lesser adverse effects. (2) Leflunomide, an immunosuppressive drug, is approved in the European community for oral treatment of rheumatoid arthritis, as a slow-acting antirheumatic agent. (3) The clinical file answers only some practical questions. (4) At a dose of 10-20 mg/day, patients start to notice the efficacy of leflunomide after 4-8 weeks. (5) One of the two available trials versus methotrexate shows that the latter is significantly more effective than leflunomide on clinical end points. The other trial, which was smaller, showed no difference between the treatments. Another trial showed no difference in clinical efficacy between leflunomide and sulfasalazine. (6) Leflunomide was more often associated with severe adverse events than methotrexate or sulfasalazine: elevated transminase levels, haematological disorders and cutaneous reactions. (7) Leflunomide is teratogenic in animals. The summary of product characteristics recommends a two-year period between conception and the end of leflunomide treatment. (8) The two-week half-life of the active metabolite of leflunomide is a major disadvantage when adverse effects occur. | |
| 11021173 | [A case of rheumatoid arthritis associated with autoimmune hemolytic anemia due to weekly | 2000 Aug | A 57-year-old woman was found to have rheumatoid arthritis (RA) in 1996. Treatment with different immunoregulatory agents, including actarit and bucillamine, produced no improvement. Therefore, combined therapy with methotrexate (MTX) (5 mg/week oral) and low-dose prednisolone (PSL) (5 mg/day) was started in April 1997. Sulindac and famotidine were also administered. In August 1997, she was admitted to our hospital because of palpitations and shortness of breath due to severe anemia. Results of laboratory studies were hemoglobin, 2.9 g/dl; reticulocyte count, 225/1000; and haptoglobin, less than 10 mg/dl. The direct and indirect Coombs'tests were positive. A diagnosis of autoimmune hemolytic anemia (AIHA) was made on the basis of the laboratory findings. Treatment with high-dose PSL (50 mg/day) was started, and the anemia improved. The hemoglobin level increased to 6.0 g/dl within the 1st week and to 12.6 g/dl 6 weeks later. We believe that the most likely explanation for this anemia was the low-dose MTX because the anemia appeared soon after treatment was started. | |
| 9396370 | [Effects of low dose methotrexate therapy in rheumatoid arthritis: a comparison of three d | 1997 Oct | The effectiveness of methotrexate (MTX) in treatment of rheumatoid arthritis (RA) was evaluated by following the course of 232 cases. The number of cases in which MTX treatment was assessed as effective amounted to 149 (64.2%), and among these the number of cases in which the effect was excellent amounted to 59 (25.4%). As for the time required to achieve the therapeutic effect, effectiveness was evident within one month in most cases and the more prominent was the result, the shorter was the time required to achieve the effect. In analysis of it's effectiveness, no relationship to the patient's background such as morbidity period, the extent of inflammation, or the period of administration of anti-rheumatic drugs was observed and this drug seems promising for treatment of severe inflammation in cases of RA with prolonged course enabling application to a wide range of patients. Also, therapeutic effectiveness was observed in a group of elderly patients, who were more than 65 years old. However, in such cases, MTX should be administered carefully because of its reported strong adverse effects. Its effectiveness and adverse effects have been shown to be dose-dependent. Therefore, as the optimum dosage of MTX, it is recommended to administer a dose of 5.0 mg/week initially for an evaluation period of two months and in those cases in which no effect is observed, the dose is then increased to 7.5 mg/week. | |
| 9587050 | Influence of biological variables upon pharmacokinetic parameters of intramuscular methotr | 1998 Apr | The pharmacokinetics of methotrexate were studied in 22 patients receiving 5-15 mg per week in a single i.m. administration for rheumatoid arthritis. The data consisted of 3 plasma levels per patient, taken at 2, 6, and 12 hours after the administration. The concentration of methotrexate was determined by fluorescence polarization immunoassay. The pharmacokinetic parameters of a 2-compartment model were determined by Bayesian estimation using the population values of Bressolle et al. [1996]. The fitted parameters were: total plasma clearance of methotrexate (CL), first-order absorption constant (ka), volume of central compartment (V1), and transfer constants between the 2 compartments (k12 and k21). Additional parameters were derived from the fitted ones: maximal concentration (Cmax), time to maximum (tmax), volume of distribution at steady-state (Vss), and terminal half-life (t1/2). Twenty-one biological covariates were considered to explain the interpatient variability. The relationships between these covariates and the pharmacokinetic parameters were investigated by principal component analysis and multiple regression analysis. About 90% of the variability of CL were explained by 4 variables (sex, age, height and serum creatinine). About 50%-70% of the variability of the other pharmacokinetic parameters were explained by a set of covariates including age, height, creatinine, creatinine clearance, and dose. The effect of dose was noticed mainly on k12, Vss, and t1/2, thus suggesting that the transfer of the drug from plasma to tissues may be nonlinear. The possibility of predicting CL with a good precision would facilitate the computation of dosage regimens in these patients. | |
| 11669156 | Practice variation in the treatment of rheumatoid arthritis among German rheumatologists. | 2001 Oct | OBJECTIVE: To describe practice variation in the treatment of rheumatoid arthritis (RA) among German rheumatologists with regard to drug and non-drug therapy. METHODS: We used data of 7,326 patients with RA registered in a national German rheumatological database in 1998. In the database, every patient with an inflammatory rheumatic disease seen at one of the German Collaborative Arthritis Centres is registered once a year with a standard clinical data form and a patient questionnaire. We compared health care provided by 29 rheumatological outpatient units. For drug and non-drug treatment unit prescription rates, ranges and outliers were calculated. Logistic regression analysis was used for case mix adjustment and for the identification of practice patterns. RESULTS: We observed variation concerning the frequency of use of single disease modifying antirheumatic drugs (DMARD). The median of the prescription rates in the 29 units for methotrexate (MTX) was 55% in 1998 (1st quartile: 51%, 3rd quartile: 63%); sulfasalazine had a median of 15% (quartiles: 10%/19%), antimalarials a median of 8% (quartiles: 5%/21%). Combination DMARD therapy was used in 11% (quartiles: 6%/18%). Prescriptions of low dose steroids (< or = 7.5 mg) had a median of 45% (quartiles: 35%/55%), and nonsteroidal antiinflammatory drugs (NSAID) had a median prescription rate of 58% (quartiles: 50%/70%). High variation was also found concerning active physiotherapy (median: 41%; quartiles 34%/55%) and passive physical measures (median 14%, quartiles 9%/37%). Differences in case mix (age, sex, rheumatoid factor, disease duration, severity, disability) only explained a small proportion of the total variation. When the units were grouped according to the frequency of prescription of DMARD combination therapy, treatment patterns could be identified. Units with higher rates of DMARD combination therapy used more drugs for the prevention and treatment of osteoporosis, more active physiotherapy but fewer NSAID and fewer passive physical therapies. CONCLUSION: Variation in drug and non-drug treatment indicates significant differences in health care provision. Trends in the drug management of RA are adopted differentially by the members of the rheumatology community. The large variability in non-drug therapies may, apart from differences in availability, suggest a lack of agreement on therapeutic effectiveness. | |
| 10513801 | Function and health-related quality of life: results from a randomized controlled trial of | 1999 Sep | OBJECTIVE: To assess the efficacy of leflunomide or methotrexate compared with placebo in improving function and health-related quality of life in patients with active rheumatoid arthritis (RA), and to examine correlations between response status (as defined by the American College of Rheumatology [ACR] response criteria) and improvement in these measures. METHODS: This 52-week, multicenter, doubleblind, controlled trial compared responses to the Health Assessment Questionnaire (HAQ), modified Health Assessment Questionnaire (MHAQ), Problem Elicitation Technique (PET), Medical Outcomes Study Short Form 36 (SF-36), and questions regarding work productivity among 3 treatment groups (leflunomide, methotrexate, and placebo). Improvement in the PET top 5 and SF-36 scales and component scores were compared with ACR response rates. RESULTS: Clinically meaningful and statistically significant (P<0.0001) improvement in measures of function and heath-related quality of life (MHAQ scores, all scales and disability index of the HAQ, weighted top 5 score of the PET, 5 of 8 scales and physical component score of the SF-36, and work productivity) was seen during treatment with leflunomide in comparison with placebo. Methotrexate administration resulted in significant improvements (P<0.05) in comparison with placebo in the MHAQ scores, HAQ disability index, weighted top 5 score of the PET, physical component score of the SF-36, and bodily pain scale. Compared with methotrexate, leflunomide administration resulted in significantly (P<0.01) more improvement in the MHAQ scores, 5 of 8 scales and disability index of the HAQ, weighted top 5 score of the PET, and 2 of 8 scales and physical component score of the SF-36. Improvements in the PET score, SF-36 physical component score, and work productivity correlated with the ACR responder rates of > or =20% and > or =50% improvement. CONCLUSION: Significant improvements in function and health-related quality of life occurred in patients with RA during treatment with leflunomide or methotrexate. These findings were clinically meaningful and correlated with the ACR response status. | |
| 10599370 | Toxicity profile of methotrexate in rheumatoid arthritis. A preliminary survey. | 1999 | A number of patients with rheumatoid arthritis attending the Rheumatology Clinic at St Luke's Hospital are currently receiving the drug methotrexate as a second line disease-modifying agent. A survey has been conducted to assess the toxicity profile of methotrexate in 33 of these patients who were followed up for at least 1 year or until they developed side effects necessitating discontinuation of treatment. Adverse effects in this group of patients included haematological ones (6%), asymptomatic elevations of liver enzymes (57%), gastrointestinal (6%) and dermatological side effects (3%). These results have been compared to larger studies performed abroad. Regular monitoring of a complete blood count and liver function tests has helped to detect the more serious side effects of methotrexate at an early stage enabling successful intervention in these patients. |