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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| 10813280 | Radiological and clinical results of longterm treatment of rheumatoid arthritis with metho | 2000 May | OBJECTIVE: To study whether the reported superior effect of methotrexate (MTX) compared to azathioprine (AZA) in retarding radiologic progression after one year in rheumatoid arthritis was sustained at 2 and 4 years. METHODS: All 64 patients enrolled in the original randomized double blind study were invited for an open extension of followup to 4 years including 4-monthly clinical and laboratory assessments and radiographs of hands, wrists, and feet at 2 and 4 years. RESULTS: After 4 years, 18 patients (58%) from the MTX group and 7 patients (21%) from the AZA group continued the initial study drug. During followup more patients (n = 21) switched from AZA to MTX than vice versa (n = 5). In an intention-to-treat analysis improvement of clinical and laboratory variables at 4 years was more pronounced in the MTX group. Mean radiologic scores increased in both treatment groups during followup. According to an intention-to-treat analysis increase in erosion score at one and 2 years in the MTX group was significantly lower than in the AZA group: after one year MTX group 1.8 versus AZA group 5.3 (p = 0.002); after 2 years MTX 3.5 versus AZA 6.5 (p = 0.05). After 4 years there was a trend toward less progression in the MTX group: MTX 6.8 versus AZA 10.8 (p = 0.09). For the total score, progression in the MTX group was less after one and 2 years. After 4 years marked radiologic progression was observed more often in the AZA group. CONCLUSION: Drug continuation after 4 years of followup was better for MTX than for AZA. In an intention-to-treat analysis the beneficial effect of MTX on radiologic progression compared with AZA was sustained after 2 years of followup. Thereafter differences between treatment groups leveled off, probably mainly due to the greater number of switches from AZA to MTX than vice versa. | |
| 9599795 | Lymphoproliferative disorders in rheumatoid arthritis patients on low-dose methotrexate. | 1998 Apr | Methotrexate is the most widely used second-line treatment in rheumatoid arthritis because of its excellent efficacy and safety profile. However, since 1991, about 100 cases of lymphoproliferative disorders have been reported in rheumatoid arthritis patients under methotrexate therapy. Four characteristics similar to those in lymphomas associated with immunodeficiency were identified during a review of the 48 cases for which detailed information is available. (1) Most cases were non-Hodgkin's B-cell lymphomas of the large cell or diffuse mixed type. (2) Extranodal involvement (55% of cases) was unusually common. (3) Evidence of Epstein-Barr infection was found in 46% of tested patients. (4) Of the 14 patients treated by methotrexate withdrawal alone, eight achieved a full remission, with follow-ups ranging from one to five years. These characteristics suggest a role for two factors: (1) the abnormalities in cell-mediated immunity seen in rheumatoid arthritis may promote latent Epstein-Barr virus infection, which may in turn lead to proliferation of malignant lymphoid cells; (2) the immunomodulatory effects of methotrexate may promote the development not only of opportunistic infections but also of Epstein-Barr virus-related lymphoproliferative disorders. There is no firm evidence to date that methotrexate has a direct oncogenic effect and no excess in malignant diseases has been reported with this drug. In conclusion, the rate of occurrence of lymphoproliferative disorders induced by low-dose methotrexate therapy remains controversial, although the characteristics of the malignancies and the possibility of a complete remission after methotrexate withdrawal militate against a chance association. Epidemiologic and other studies are needed to clarify this issue. | |
| 9916387 | Comparative studies of quality and bioavailability of methotrexate in Thai patients with r | 1998 Dec | The bioavailability of the two generic methotrexate oral preparations (Emtrexate, Pharmachemie Company, Holland and Methotrexate Remedica, Remedica, Cyprus as the test preparations), were compared to the innovator (Methotrexate Lederle, Lederle, U.S.A. as the reference) in 10 patients with rheumatoid arthritis. A single 7.5 mg oral dose of each preparation was given to the subjects in a randomized, double-blind, three-period crossover design with a 1 week washout period. Serum methotrexate concentrations were determined by using Fluorescence Polarization Immunoassay (Abbott TDx). No significant differences in pharmacokinetic parameters (AUC, Cmax, and Tmax) were observed between the test and reference preparations. The mean and 90 per cent CI of the ratio Emtrexate/Methotrexate Lederle and Methotrexate Remedica/Methotrexate Lederle of the Cmax, AUC0-8, and AUC0-alpha were 0.93 (0.87-1.00), 0.9 (0.82-0.98), 0.88 (0.79-0.99) and 0.97 (0.93-1.02), 0.95 (0.90-0.99), 0.94 (0.86-1.02), respectively. These values were well within the acceptable bioequivalence range of 0.8-1.25. The mean and 90 per cent CI of Tmax difference between Emtrexate-Methotrexate Lederle and Methotrexate Remedica-Methotrexate Lederle also overlapped the stipulated bioequivalence range of the Tmax differences of +/- 0.25 hour. Thus, Emtrexate and Methotrexate Remedica were considered bioequivalent to the reference Methotrexate Lederle regarding the rate of absorption and the extent of absorption. | |
| 11517739 | [Double-blind trial of the effectiveness of antibodies to interferon-gamma and tumor necro | 2001 | AIM: Objective evaluation of the effectiveness and tolerance of antibodies to interferon-gamma (TNF-gamma) vs those to tumor necrosis factor-alpha (TNF-a) and placebo in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: A double blind randomised controlled trial of effectiveness and tolerance of anticytokine antibodies was conducted in 30 patients with active RA. The drugs were given i.m. for 5 consecutive days. The results were assessed on day 7 and 28. RESULTS: Antibodies to both cytokines produced a marked therapeutic effect in RA, much greater than placebo effect. Improvement by day 7 was achieved in 9, 7 and 2 patients on anti-TNF-a, anti-INF-g and placebo, respectively. By day 28 in 8, 8 and 0 patients, respectively. Tolerance of anticytokines was good. Significant differences between the results of treatment with anti-INF-g and anti-TNF-a were not found. CONCLUSION: Administration of antibodies to INF-a proved ineffective and well tolerated method in the treatment of severe RA resistant for a number of standard basic drugs. Anti-IFN-a holds great promise when used in combination with classic antirheumatoid drugs, primarily with methotrexate. | |
| 10682647 | [Pharmacotherapy of patients with (early) rheumatoid arthritis]. | 2000 Jan 29 | As soon as the diagnosis 'early rheumatoid arthritis (RA)' is made, a disease-modifying antirheumatic drug (DMARD) should be prescribed without delay. Methotrexate in dosages up to 30 mg once weekly is being used more frequently than in the past, also in early RA. Combination therapy with DMARDs is indicated in case of insufficient effect of a single DMARD. Combinations with methotrexate appear to be especially effective, like methotrexate and cyclosporin. A novel effective DMARD is leflunomide. In the near future promising biologicals will probably be applied in clinical daily practice, presumably in combination with conventional DMARDs. New non-steroidal anti-inflammatory drugs (NSAIDs) have been developed that are probably safer than conventional NSAIDs. If the recent finding that glucocorticoids are able to inhibit joint damage in (early) RA will be confirmed, prednisone might be used more often in (early) RA. Bone marrow transplantation in RA is still experimental. | |
| 9549386 | [Therapy of refractory rheumatoid arthritis. Cyclosporin and methotrexate combination]. | 1998 Jan | Rheumatoid arthritis (RA) is a chronic multisystemic disease affecting mainly the joints and characterised by a poor prognosis. In a four month open study we evaluated the efficacy and tolerability of a combination therapy in 14 patients with active and refractory RA (non responsive to MTX or CsA monotherapy). After three pulses of methyl-prednisolone (125 mg/die i.v. for 3 days), at day the 4 patients received methotrexate (MTX 15/mg/week p.os) and cyclosporine (CsA 3 mg/kg/day p.os). At the end of treatment period, patients had a statistically significant improvement in the tender-joint count (Ritchie Index) in the swollen-joint count and in the pain as recorded on a 100-mm visual-analogue scale. Following the criteria of the American College of Rheumatology for response to treatment in RA, 6 patients (60%) met these criteria, whereas 2 had a worsening. We could not detect any clear difference in serological parameters (ESR, CRP and Hb levels) between the beginning and the end of the therapy. A significant difference in the score of edema/joint effusion was documented at the RM analysis. Side-effects were not substantially increased as compared to MTX or CsA in single therapy. Combination therapy with CsA and MTX seems to be a safe and effective treatment for patients with active and refractory RA. | |
| 10328573 | Disease-modifying antirheumatic drugs. | 1999 May | Rheumatologists now seem to accept that early treatment of patients with rheumatoid arthritis with disease-modifying antirheumatic drugs is required if erosions are to be prevented. Methotrexate remains the most popular disease-modifying antirheumatic drug and is used in the most popular combination treatments, although the dose needs to be reduced in the elderly and those with renal dysfunction. The combination of sulfasalazine, methotrexate with reducing high-dose prednisolone, is demonstrated to be cost-effective in patients with rheumatoid arthritis, but although several other combinations have been reported effective in patients with rheumatoid arthritis, most trials do not have the power to provide a definitive answer as to the best combination available, if one exists. | |
| 9340953 | [Development and evaluation of a modified version of the Larsen method for evaluating roen | 1997 May | AIM OF THE STUDY: To develop and evaluate a modification of the Larsen scoring method aimed at a clear definition of the different grades and a better correlation of the numerical scale with the amount of joint destruction. DESCRIPTION OF THE METHOD: While the original method described by Larsen is based on a comparison with standard reference films the modification defines the different grades semiquantitatively by the amount of destruction of the joint surface: grade II is a destruction (erosion) of the joint surface of up to 25%, in grade III it is 26-50%, in grade IV 51-75% and in grade V over 75%. Grade I is characterized by soft tissue swelling and in addition subchondral osteoporosis and remains unchanged compared with the original method. 32 joints of the hands, wrists and forefeet are counted summing up to a total score of 0-160. Examples for different joints are given. EVALUATION OF THE METHOD: Standard ap-x-rays of hands, wrists and forefeet of 24 patients with early erosive rheumatoid arthritis at baseline (T0) and after 36 months (T1) were graded by two investigators (G.H. and R.R.). The difference of the scoring between both observers (inter-observer-difference) was related to the difference between the two timepoints (T0 and T1) in the same patient (intra-patient-difference) by means of a hierarchical analysis of variance (ANOVA). The intra-patient variance (from T0 to T1) was 259.3, which is 8 times greater than the inter-observer-variance of 32.1. The square root of intra-patient-standard deviation (16.1) and inter-observer-standard deviation (5.7) is 2.8. These data show that the progression between T0 and T1 is real. The method was easily applicable to patients in a 2-year-DMARD-trial with x-rays at baseline after 6, 12 and 24 months, showing a slowing of radiologic progression after month 6 under treatment with parenteral gold and methotrexate. CONCLUSION: The modification of Larsen's scoring method is a reliable measure to assess radiologic progression in patients with RA. Possibilities for further improvement are discussed. | |
| 9572710 | Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxic | 1998 Apr | OBJECTIVES: To provide an update of the current knowledge of the mechanism of action of low-dose methotrexate (MTX) in the treatment of patients with rheumatoid arthritis (RA), with an emphasis on the mechanisms involved in toxicity. We also considered strategies currently used to prevent or decrease toxicity of MTX. METHODS: We reviewed the literature dealing with the subjects of MTX treatment of RA, the mechanisms of action of low-dose MTX regarding efficacy and toxicity, and strategies used to prevent or decrease MTX toxicity. RESULTS: MTX is a fast working and effective second-line antirheumatic agent (SLA). Its use is limited mainly because of side effects. The mechanisms of action regarding efficacy and toxicity are probably determined by different metabolic pathways. Recent data indicate that the antiinflammatory effect of MTX is mediated by adenosine. However, MTX side effects can only partly be explained by folate antagonism and may also depend on its action on other related metabolic pathways. The latter include the homocysteine-methionine-polyamine pathway and purine metabolism. Variants in these metabolic routes (ie, the C677T mutation in the methylene-tetrahydrofolate reductase [MTHFR] gene), may predispose to the development of side effects. Currently the most promising strategy to decrease or prevent toxicity of MTX is concomitant prescription of folic acid or folinic acid. Other strategies are currently under investigation. CONCLUSIONS: MTX benefits a majority of RA patients. Approximately 30% of patients, however, abandon treatment because of drug-related side effects. Folic acid or folinic acid likely reduces MTX toxicity. More data, however, are needed to evaluate a potential detrimental effect on the antirheumatic efficacy of MTX. | |
| 10769433 | Rheumatoid arthritis and osteoporosis. | 2000 | Some controversial issues in the current literature in relation to osteoporosis and rheumatoid arthritis are updated and discussed. 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 severity. The threshold dose for corticosteroid-induced osteoporotic fractures is the cumulative rather than the actual dose. Statements based on quantitative 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, especially in 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. | |
| 10743802 | Modeling therapeutic strategies in rheumatoid arthritis: use of decision analysis and Mark | 2000 Mar | OBJECTIVE: The management of patients with rheumatoid arthritis (RA) is controversial, with a number of different proposed treatment strategies based on different conceptions of the natural history of the disease and different interpretations of the efficacy and effectiveness of the drugs used for treatment. We attempted to develop a theoretical framework to assess the effectiveness of different treatment regimens for RA. METHODS: We used decision analysis to structure the problem of comparing sequential monotherapy to a combination strategy. Subsequently, we used 3 different estimates of drug effectiveness: one from expert rheumatologists; a metaanalysis; and a recent nationwide survey of American rheumatologists, in a Markov model. Last, we utilized published duration of therapy data to model drug treatment over time. RESULTS: Estimates of drug effectiveness differed substantially among rheumatologists, but regardless of the estimates and the treatment strategy used, the model predicted over 90% of patients improved by the 3rd drug trial. Over time, treatment patterns in our model resemble the "sawtooth" pattern previously observed. CONCLUSION: Treatment strategies in RA are difficult to model because of uncertainty in both the structure of the model and the data needed to perform the analysis. These models tend to overestimate the effectiveness of drug sequences because of nonindependence between therapies, probably due to sequence effects, a change in responsiveness over time, or resistant subgroups. Our preliminary analysis suggests that the most effective agent, possibly methotrexate, should be used first if the objective is to get as many patients into remission as quickly as possible. | |
| 10813279 | Factors influencing length of time taking methotrexate in rheumatoid arthritis. | 2000 May | OBJECTIVE: Duration of therapy has been suggested to represent a measure of effectiveness. Life table analyses of therapy with methotrexate (MTX) in rheumatoid arthritis (RA) have indicated a longer duration than with other drugs. However, individual patients continue taking MTX for different periods of time. We assessed the influence of patient variables at treatment onset upon subsequent duration of MTX therapy. METHODS: Patients with RA (n = 437) from 8 North American databank centers beginning MTX therapy after January 1, 1988, were followed prospectively. Age at onset of MTX treatment, sex, years of education, age at onset of disease, years with disease, number of comorbid conditions, number of disease modifying antirheumatic drugs (DMARD) and nonsteroidal antiinflammatory drugs (NSAID) taken just prior to MTX. disability level, pain, and global assessment prior to starting MTX were used in univariate Kaplan-Meier analyses to predict number of months taking MTX alone. An index that divided the patients into risk strata for predicting duration of therapy was constructed to be clinically useful. RESULTS: The median number of months continuing MTX without addition of other DMARD was 41 months and the median for the total course taking MTX was 52 months. The retention rate was lowest for patients with the most negative initial health state. High level of initial pain, long duration of disease, and not using a DMARD just prior to MTX were associated with low retention rate and can be used to predict expected durations of MTX treatment ranging from 17 to 52 months. For practical guidance in clinical decisions an index was computed based on the predictor variables: level of initial pain, duration of disease, and number of DMARD; this index identifies subgroups with very different durations taking MTX alone. Disease duration at baseline was strongly related to time taking MTX alone and could therefore also be used as a simplified rule in clinical work. CONCLUSION: Expected duration of MTX treatment is influenced by clinical variables, and these may suggest those patients likely to have more or less satisfactory experiences with MTX. The time taking drug alone (therapeutic segment) may be a more logical and sensitive indicator of effectiveness than the total course on the medication. | |
| 10888709 | Enhanced production of tissue inhibitor of metalloproteinases by peripheral blood mononucl | 2000 Jun | OBJECTIVE: To determine the effects of methotrexate (MTX) treatment of rheumatoid arthritis (RA) patients (a) on the circulating levels and (b) on the ex vivo production of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) by peripheral blood mononuclear cells (PBMNC). METHODS: Circulating levels, spontaneous ex vivo and in vitro production of MMP-1, TIMP-1 and interleukin-6 (IL-6) were assessed by immunoassays in sera and culture supernatants of PBMNC derived from 27 patients with active RA before and 3 months after beginning MTX treatment and from seven healthy subjects. The production and serum levels of MMP-1, TIMP-1 and IL-6 were correlated to the clinical response. RESULTS: PBMNC of RA patients showing >/= 20% improvement of the Paulus index after 3 months of MTX treatment (responders; n = 16) exhibited a significantly enhanced production of spontaneous TIMP-1 ex vivo which was associated with the enhanced synthesis of IL-6. In contrast, PBMNC of 11 patients with <20% improvement and/or progression of disease showed a marked reduction of TIMP-1 and IL-6 secretion. Circulating levels of TIMP-1 remained unchanged in both groups whereas serum IL-6 levels declined in the responder group. MMP-1 was detectable only in very few culture supernatants and RA sera. Moreover, PBMNC of healthy donors revealed that MTX also stimulated TIMP-1 and IL-6 release in vitro, IL-6 being partially responsible for the induction of TIMP-1 production. CONCLUSIONS: Both ex vivo and in vitro, the enhanced TIMP-1 production by PBMNC of RA patients and healthy individuals upon MTX treatment is associated with simultaneously enhanced IL-6 release, and enhanced ex vivo production of both is clearly associated with short-term clinical efficacy. This may reflect disease remission and favourable effects on host defence mechanisms against aberrant inflammation and extracellular matrix turnover in RA patients undergoing MTX treatment. | |
| 10808674 | Initial disease modifying antirheumatic drugs and prednisolone prescriptions for patients | 2000 Mar | OBJECTIVE: To compare patterns and time trends of initial disease-modifying antirheumatic drugs (DMARDs) and prednisolone prescriptions for patients with rheumatoid arthritis (RA) by the rheumatologists at King Chulalongkorn Memorial Hospital, Bangkok, Thailand over a 15-year period, as well as their side effects. METHOD: Medical records of all patients with RA seen at the Rheumatology Clinic from January 1983 to June 1997 with a duration of follow-up of 6 months or more were reviewed. Information on the disease, initial DMARDs prescriptions and their side effects, prednisolone use, dosage and side effect(s) were focused and compared among three 5-year periods (1983-1987, 1988-1992 and 1993-1997). RESULTS: 236 patients were included in this study. There were 44, 82 and 110 patients in the first, second and third period, respectively. Methotrexate (MTX) was the most frequently prescribed DMARD in all time periods. Dapsone and intramuscular (i.m.) gold were prescribed in the first period while antimalarial drugs and sulfasalazine (SSZ) were increasingly used in the second and third periods. Combination treatment of DMARDs was first used in the third period. Side effects from MTX were observed in patients with a longer duration of treatment (p < 0.05). Patients prescribed combined DMARDs did not develop more side effects compared with those who had monotherapy. Prednisolone was prescribed in 57.2 per cent of the patients, most being newly prescribed at the clinic. Mean starting dose of prednisolone was 8.9 mg per day. 64 patients took prednisolone together with non-steroidal antiinflammatory drugs (NSAIDs). Gastrointestinal side effects did not increase in these patients. CONCLUSION: MTX was the most frequently prescribed DMARDs regardless of the time period. Antimalarial drugs, SSZ and combination of DMARDs (most were MTX + chloroquine) have been prescribed more in the last 5 years, while dapsone, auranofin and i.m. gold were rarely used as initial DMARDs. Low dose prednisolone was prescribed in more than half of the patients with RA. Side effects from DMARDs and prednisolone found in this study were comparable to previous reports. | |
| 11001380 | Efficacy and safety of leflunomide in active rheumatoid arthritis. | 2000 Jun | Leflunomide, the newest disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA), inhibits de novo pyrimidine biosynthesis. In two placebo-controlled trials, leflunomide was superior to placebo and comparable to sulphasalazine and methotrexate for improving the signs and symptoms of RA, significantly improved functional ability compared with placebo, sulphasalazine and methotrexate, and was superior to methotrexate and comparable to sulphasalazine in slowing radiographically assessed disease progression. In a multinational trial vs methotrexate, leflunomide showed an American College of Rheumatology (ACR) response rate similar to that in placebo-controlled trials. The ACR response rate with methotrexate was significantly greater. Differences between these trials included methotrexate dosing regimens, folate usage and disease duration. Common adverse events with leflunomide included gastrointestinal symptoms, allergic reactions, alopecia and elevated liver enzyme levels. No long-term safety issues were reported with leflunomide at 2 yr. Efficacy of leflunomide was maintained at 2 yr. Leflunomide is a safe and efficacious addition to the roster of anti-rheumatic drugs. | |
| 10660945 | Cyclosporine A pharmacokinetics in rheumatoid arthritis patients after 6 months of methotr | 1999 Dec | To evaluate the effects of a 6-month methotrexate (MTX) treatment period on cyclosporine A (CsA) pharmacokinetics were subsequently added in patients with rheumatoid arthritis (RA) in comparison with patients treated with CsA only, CsA was administered to 30 subjects with RA (group A) treated with MTX (10 mg week-1 i.m.) for 6 months and to 30 patients (group B) who received no MTX treatment. The mean doses +/- SD of CsA used in groups A and B were 3.2 +/- 0.5 and 3.3 +/- 0.4 mg kg-1, respectively. CsA levels were determined in whole blood by means of a fluorescence polarization immunoassay (FPIA) method with a specific monoclonal antibody. The following pharmacokinetics parameters were calculated: area under the curve from 0 to 24 h (AUC0-24), half-life of the elimination phase (T1/2 beta), total body clearance CL.F-1; V.F-1 and apparent volume of distribution (Vd beta). The mean blood concentrations and the pharmacokinetic parameters calculated in group A did not present significant statistical differences in comparison to group B. In conclusion, a 6-month MTX therapy does not produce liver function modifications to such an extent as to modify the pharmacokinetics of CsA subsequently added. Therefore, from a clinical pharmacological point of view, an MTX-CsA cotreatment appears feasible. | |
| 9448591 | Decrease of interleukin 6 during the first 12 months is a prognostic marker for clinical o | 1997 Dec | The aim of this study was to determine prognostic markers for the outcome after 36 months of therapy with disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) and to study serial cytokine serum levels. During 36 months, 20 patients receiving DMARDs (nine patients gold sodium thiomalate and 11 patients methotrexate, no comparison undertaken) were followed for clinical and laboratory data. Investigation at baseline, 12, 24 and 36 months, included clinical, radiological and laboratory parameters such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha (TNF-alpha), IL-1 receptor antagonist (IL-1RA) and IL-2. During the 3 yr of therapy, the patients showed significant clinical improvement and decline of ESR, CRP, and serum levels of IL-6 and IL-2. The decrease in IL-6 serum levels during the first year of therapy correlated significantly with the decrease, after 36 months, in the number of inflamed joints (r = 0.7608, P < 0.005), Lansbury index (r = 0.6642, P < 0.005) and morning stiffness (r = -0.6561, P < 0.005). In contrast to IL-6 or IL-2, TNF-alpha and IL-1RA did not vary significantly during the 3 yr of therapy. During 36 months of therapy, patients treated with DMARD showed significant improvement of clinical parameters and a trend for delayed progression of radiographic damage. The decrease in IL-6 concentration in serum during the first 12 months was the best prognostic marker for the clinical outcome after 36 months of DMARD therapy. | |
| 9272292 | Effect of treatment with methotrexate, hydroxychloroquine, and prednisone on lymphocyte po | 1997 Jul | OBJECTIVE: Polyamines are increased in activated lymphocytes, including peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA), and are important in modulating immune-mediated cellular responses. In vitro studies have suggested that methotrexate (MTX) interferes with polyamine synthesis. This study evaluated the in vivo polyamine response to MTX compared to other anti-arthritic agents, and correlated it with the clinical and immunological response. METHODS: The polyamine content of PBL was determined in 14 RA patients at initiation of treatment with MTX (n = 8), hydroxychloroquine (HCQ) (n = 3), or prednisone (n = 3), and then monthly for four months. IgM rheumatoid factor (RF) synthesis by PBL in vitro was assessed and tender joints were counted monthly. RESULTS: Polyamines (spermine and spermidine) decreased by 55% at three months in the MTX group compared to 4% and 9% in the HCQ and prednisone groups, respectively (p < 0.01). However, group differences in the clinical and immunological response were not significant. In the MTX group there was a positive correlation between polyamine levels and the joint count. Such a correlation was not observed in the other groups. CONCLUSION: These data suggest that MTX interference with the polyamine pathway is not shared by prednisone and HCQ, and is associated with its beneficial effect in RA. | |
| 9480466 | [The effect of low dose methotrexate on the course of rheumatoid arthritis--four years of | 1997 | Ninety-six patients with refractory rheumatoid arthritis were treated with methotrexate for 48 months. We analyzed the effect of low doses of methotrexate (7.5-15 mg weekly) on the activity of the disease and on the progression in damage score. Clinical improvement was observed few weeks after the study was introduced. Following 48 months observation only 32 (33%) remained in the study. Seven of them needed additionally prednisone administration. In 64 (67%) patients the drug was withdrawn: in 18 (19%) due to the side effects, in 24 (25%) due to the lack of effectiveness, in 22 (23%) due to other reasons. Methotrexate did not affect the progression of damage score in our patients. Methotrexate appeared to be usefull drug in the treatment of rheumatoid arthritis, however clinical improvement was observed only during drug administration. After discontinuous of the therapy a flare of the disease was observed. | |
| 10782811 | Matrix metalloproteinase-3 serum levels are correlated with disease activity and predict c | 2000 Apr | OBJECTIVE: To demonstrate that serum matrix metalloproteinase-3 (MMP-3) is a variable associated with disease activity and with the response to treatment in rheumatoid arthritis (RA). METHODS: Serum MMP-3 levels were measured and compared to biological and clinical disease activity variables in 20 patients with active RA assessed serially during a one year prospective open label trial with methotrexate or tenidap. RESULTS: MMP-3 levels were significantly correlated with C-reactive protein (CRP) and interleukin 6 serum levels as well as with the disease activity score (DAS), not only at start in untreated patients but also during the 12 month followup period in both treated groups. Early changes (after 0.5, 1, 2, or 3 months) in MMP-3 levels were significantly associated with change in DAS observed 4 to 6 months later. CONCLUSION: In addition to CRP, a systemic marker of inflammation, serum MMP-3 may serve as a consistent synovial derived marker of RA disease activity, early changes of which predict disease outcome. |