Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8308768 | A comparison of low dose methotrexate bioavailability: oral solution, oral tablet, subcuta | 1993 Nov | OBJECTIVE: To compare the relative bioavailability of low dose methotrexate (MTX) administered as tablet, oral solution, and subcutaneous (sc) injection to that of intramuscular (im) injection in patients with rheumatoid arthritis (RA). METHODS: Twelve patients meeting the American College of Rheumatology criteria for RA had serial blood MTX concentration samples drawn over a 24-h period after receiving their normal weekly MTX dose. Relative bioavailability (F) of the tablet and oral solution formulations was determined by comparison of the area under the time-versus-serum-concentration curves (AUC) for the 2 different oral formulations as a percentage of the AUC for im injection. Also, relative bioavailability of the sc formulation was compared to im in 6 of the patients. RESULTS: Mean F for the oral tablet was 0.85, while that for the oral solution was 0.87. Both oral formulations showed a statistically significant difference in mean F when compared to im (tablet vs im, p = 0.002, oral solution vs im, p = 0.009). No statistically significant difference, however, was found in mean relative bioavailability between tablet and solution (p = 0.744). The mean F for sc was 0.97; no statistically significant difference existed between the mean F values for the sc and im routes of administration (p = 0.657). CONCLUSIONS: Our data suggest the oral solution may be substituted for tablet dosing and sc injection substituted for im. Thus, a variety of different dosing methodologies may be considered providing the most appropriate route in each patient, given issues of compliance, medication cost, and preference. | |
| 8776373 | Reversible cutaneous lymphoma occurring during methotrexate therapy. | 1996 Jul | A B-cell lymphoma, restricted to the skin, developed in a 58-year-old man receiving methotrexate for non-rheumatoid peripheral arthritis, with the simultaneous occurrence of a cytolytic hepatitis and carcinoma of the lung. Two weeks after methotrexate was stopped, both the skin tumour and the hepatitis disappeared spontaneously, with no recurrence during a 12-month follow-up period. Immunoglobulin gene rearrangement was shown by polymerase chain reaction (PCR) but in situ hybridization failed to reveal neoplastic cells positive for Epstein-Barr virus (EBV). | |
| 8929481 | Myelodysplastic syndromes and acute myeloid leukemia in connective tissue disease after si | 1996 Nov | Cytopenias are typical of patients with connective tissue disease (CTD) and are usually related to autoimmune phenomena. In some cases, cytopenia may be the result of treatment with cytotoxic agents. Although multi-drug therapy is known to produce myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) in patients with CTD, treatment with single-agent therapy, particularly methotrexate, has rarely been associated with secondary MDS or AML. Blood and marrow samples were studied from 3 men and 5 women with rheumatoid arthritis (5 cases), Behcet's disease (2 cases), and systemic lupus erythematosus (1 case) developing MDS or AML after methotrexate (5 cases), chlorambucil (2 cases), and cytoxan (1 case). The durations of CTD ranged from less than 6 months to more than 10 years. Five patients (63%) presented with MDS including refractory anemia (RA), refractory thrombocytopenia (RT), refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML), and RAEB in transformation. Patients with RT, CMML, and RAEB in transformation developed AML. Of six patients presenting with or developing AML, four had AML with differentiation (FAB M2), one acute myelomonocytic leukemia (FAB M4), and one M4Eo. Inv 16 was seen in the M4Eo and t(8;21) in one case of M2. Four of six patients are alive up to 6 years after diagnosis of AML. One of three patients with MDS is alive 6 months after diagnosis of MDS. Cytopenias in patients with CTD may be due to therapy-related MDS or AML occurring in a setting of single-agent chemotherapy, including methotrexate. | |
| 8596147 | The effects of nonsteroidal antiinflammatory drugs on methotrexate (MTX) pharmacokinetics: | 1995 Nov | OBJECTIVE: To determine the pharmacokinetics of methotrexate (MTX) with and without nonsteroidal antiinflammatory drugs (NSAID) at a 7.5 mg dose and higher usual maintenance doses of the drug. To determine the difference in pharmacokinetic variables when salicylate and nonsalicylate NSAID are administered with MTX at these doses. METHODS: Thirty patients receiving MTX chronically underwent a study of MTX pharmacokinetics after 7.5 mg doses of MTX with their usual NSAID and after the NSAID were withheld for 5 half-lives. Sixteen additional patients underwent pharmacokinetics studies with and without NSAID while receiving their usual weekly maintenance dose of MTX of 16.6 (3.6) mg (Mean +/- SD). RESULTS: No significant differences in pharmacokinetic variables were observed with and without NSAID at the 7.5 mg weekly dose of MTX. When patients received usual maintenance doses of MTX the renal clearance of MTX NSAID was 91.7 (26.4) ml/min versus 115.3 (34.4) ml/min without NSAID (p = 0.004). Creatinine clearance in patients taking usual maintenance doses increased from 77.5 (13.9) ml/min with NSAID to 95.3 (26.3) ml/min without NSAID (p = 0.05). A reduction in renal clearance of MTX was observed with maintenance dose MTX in both the 4 patients taking salicylates (p = 0.016) and the 12 patients taking nonsalicylate NSAID (p = 0.024). CONCLUSION: NSAID produce significant decreases in renal clearance of MTX and creatinine when patients consume their usual weekly dose of the drug, but not when they take a 7.5 mg dose. This effect is likely to achieve clinical relevance across the dose ranges used to treat patients with rheumatoid arthritis. | |
| 8584484 | Pharmacokinetic studies of methotrexate in plasma and synovial fluid following i.v. bolus | 1995 Oct | PURPOSE: The pharmacokinetic properties of methotrexate (MTX) in the plasma and synovial fluid (SF) after bolus i.v. and topical administration were studied in dogs to assess the feasibility of topical delivery of MTX for the treatment of rheumatoid arthritis. METHODS: A MTX gel in Poloxamer 407 containing an absorption enhancer was formulated and topically applied on the elbow and stifle joints of dogs. SF was collected by inserting a needle with syringe into the joint space. Drug concentrations in the plasma, SF and muscle tissues were determined using a HPLC method with fluorimetric detection. RESULTS: Peak MTX concentrations in SF occurred at 38 +/- 5 min following bolus i.v. dose, indicating the presence of a substantial diffusion barrier between the plasma and SF. The plasma/SF concentration ratios of 1.16 +/- 0.25 were maintained after the attainment of distribution equilibrium between the two compartments. The t1/2 values in the plasma (11.2 +/- 1.2 hr) and SF (12.7 +/- 3.7 hr) were similar during the elimination phase, while the MRT in SF (3.24 +/- 0.21 hr) was longer than that in plasma (2.56 +/- 0.20 hr), probably due to the slow distribution of MTX to SF. After topical dose, MTX concentrations in plasma reached the steady state at approximately 4 hr, lasting for approximately 20 hr. The bioavailability of MTX from the gel was 11.8 +/- 3.3% of the applied dose, but muscle tissues beneath the gel application site had significantly higher levels of MTX than untreated muscle tissues. There was no statistical difference in SF concentrations of MTX between drug treated and untreated joints 24 hr after topical dose. CONCLUSIONS: Topical delivery of MTX in a hydrophilic gel achieved a sustained C/t profile in plasma and higher drug levels in muscle tissues underneath the dosing site, implicating the potential therapeutic value of the topical formulation. | |
| 8174459 | Drug-induced pulmonary disease. | 1994 May | Drug-induced disease of any system or organ can be associated with high morbidity and mortality, and it is tremendously costly to the health care of our country. More than 100 medications are known to affect the lungs adversely, including the airways in the form of cough and asthma, the interstitium with interstitial pneumonitis and noncardiac pulmonary edema, and the pleura with pleural effusions. Patients commonly do not even know what medications they are taking, do not bring them to the physician's office for identification, and usually do not relate over-the-counter medications with any problems they have. They assume that all nonprescription drugs are safe. Patients also believe that if they are taking prescription medications at their discretion, meaning on an as-needed basis, then these medications are also not important. This situation stresses just how imperative it is for the physician to take an accurate drug history in all patients seen with unexplained medical situations. Cardiovascular drugs that most commonly produce a pulmonary abnormality are amiodarone, the angiotensin-converting enzyme inhibitors, and beta-blockers. Pulmonary complications will develop in 6% of patients taking amiodarone and 15% taking angiotensin-converting enzyme inhibitors, with the former associated with interstitial pneumonitis that can be fatal and the latter associated with an irritating cough that is not associated with any pathologic or physiologic sequelae of consequence. The beta-blockers can aggravate obstructive lung disease in any patient taking them. Of the antiinflammatory agents, acetylsalicyclic acid can produce several different airway and parenchymal complications, including aggrevation of asthma in up to 5% of patients with asthma, a noncardiac pulmonary edema when levels exceed 40 mg/dl, and a pseudosepsis syndrome. More than 200 products contain aspirin. Low-dose methotrexate is proving to be a problem because granulomatous interstitial pneumonitis develops in 5% of those patients receiving it. This condition occurs most often in patients receiving the drug for rheumatoid arthritis, but it has been reported in a few patients receiving it for refractory asthma. Chemotherapeutic drug-induced lung disease is almost always associated with fever, thus mimicking opportunistic infection, which is the most common cause of pulmonary complications in the immunocompromised host. However, in 10% to 15% of patients, the pulmonary infiltrate is due to an adverse effect from a chemotherapeutic agent. This complication is frequently fatal even when recognized early.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 7662029 | The antiinflammatory effects of an adenosine kinase inhibitor are mediated by adenosine. | 1995 Aug | OBJECTIVE: The acute antiinflammatory effects of methotrexate are mediated, at least in part, by increased extracellular adenosine concentrations at inflamed sites. This observation suggests that other agents that increase extracellular adenosine concentrations might also reduce inflammation. Since adenosine can be rapidly taken up by cells, phosphorylated by adenosine kinase, and maintained intracellularly as adenine nucleotides, we investigated whether a potent inhibitor of adenosine kinase, GP-1-515, could increase exudate adenosine concentration and thereby diminish inflammation in the murine air pouch model of inflammation. METHODS: We studied the effect of various oral doses of GP-1-515 on carrageenan-induced inflammation in air pouches induced on BALB/c mice. Adenosine concentration in pouch exudates was determined by high performance liquid chromatography, and intensity of inflammation was determined by leukocyte counts in the exudate fluid. RESULTS: There was a greater concentration of adenosine in the pouch exudates of animals treated with GP-1-515 than of those treated with saline (P < 0.002). GP-1-515 inhibited, in a dose-dependent manner (P < 0.01), leukocyte accumulation in the murine air pouch in response to carrageenan. Inhibition of inflammation by GP-1-515 in this model depended upon increased adenosine concentration in the inflamed pouch since injection of adenosine deaminase into the air pouch with the carrageenan completely reversed the antiinflammatory effects of GP-1-515 at all doses of GP-1-515 tested. Moreover, as previously demonstrated, the antiinflammatory effects of adenosine were mediated via occupancy of adenosine A2 receptors, since the specific adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine, but not the A1 receptor antagonist 8-cyclopentyl-dipropylxanthine, completely reversed the antiinflammatory effects of GP-1-515. GP-1-515 also decreased tumor necrosis factor alpha levels in the air pouch exudates by 51%, most likely as a result of the direct action of adenosine on macrophages. CONCLUSION: These results indicate that the antiinflammatory actions of GP-1-515 are mediated by adenosine. The development of agents that promote adenosine release at sites of inflammation is a novel strategy for the treatment of inflammatory diseases such as rheumatoid arthritis. | |
| 7932104 | [Highly sensitive analytical procedure for methotrexate and its main metabolite 7-hydroxym | 1994 Aug | Recently, methotrexate (MTX) low dose therapy (5-10 mg/m2) has been used for the treatment of patients with rheumatoid arthritis. Hence a practical and sensitive high-performance liquid chromatographic method for the determination of MTX and its main metabolite 7-hydroxymethotrexate (7-OH-MTX) in human serum has been studied. After deproteinization with perchloric acid followed by the addition of pH 5.0 acetate buffer, the serum sample was purified by solid-phase extraction on a Sep-Pak C18 cartridge. The analyte was chromatographed on a reversed-phase Inertsil ODS-2 column using a phosphate buffer-acetonitrile at pH 3.0 system as the mobile phase, and the effluent from the column was monitored at 303 nm. Gradient elution was employed to increase the sensitivity for 7-OH-MTX. A good linear relationship between peak height and concentration was found for the two compounds in the range 2.5 to 100 ng/ml of the human serum, and the detection limits were about 1 ng/ml for the two compounds. The day-to-day coefficients of variation assay were 2.3% (20 ng/ml) and 4.4% (100 ng/ml) for MTX and 4.6% (20 ng/ml) for 7-OH-MTX. The present method was successfully applied to the analysis of the serum after a single oral administration of MTX 2.5 mg tablet to male dogs. MTX was rapidly absorbed, reached to the maximal level at about 1.4 h and thereafter decreased monoexponentially with a half-life of about 1.4 h. A metabolite, 7-OH-MTX was not detected in the serum up to 24 h post dose. | |
| 8609118 | Nitric oxide: an important articular free radical. | 1996 Feb | Nitric oxide is a small molecule that is synthesized by a family of enzymes, the nitric oxide synthases, and is overproduced in rheumatoid arthritis and osteoarthrosis. The aim of this investigation was to elucidate the potential sources of nitric oxide in joint tissues and to determine if the production of nitric oxide could be inhibited by dexamethasone or methotrexate, two agents that inhibit other forms of inducible nitric oxide synthase. Methotrexate inhibits the synthesis of biopterin, which is a co-factor for nitric oxide synthase. Explants of human and bovine cartilage and cultured chondrocytes released large amounts of nitrite, the stable end product of nitric oxide, when stimulated with endotoxin, interleukin-1 beta, or tumor necrosis factor-alpha. The production of nitrite was time-dependent and endotoxin, interleukin-1 beta, and tumor necrosis factor-alpha dose-dependent and was inhibited by the nitric-oxide-synthase inhibitors N omega-nitro-L-arginine methyl ester and aminoguanidine. The inducible nitric oxide synthase in bovine chondrocytes was calcium-dependent and was inhibited by high concentrations of methotrexate or dexamethasone. No constitutive nitric-oxide-synthase activity and little or no inducible nitric-oxide-synthase activity were demonstrable in explants or cell cultures derived from menisci. Fresh explants of bovine articular synovial tissue constitutively released nitrite that was inhibited by N omega-nitro-L-arginine methyl ester, but the release could not be enhanced by endotoxin, interleukin-1 beta, or tumor necrosis factor-alpha. There was no constitutive or inducible production of nitrite by explants or cells derived from the synovial tissue or shoulder capsule of a human or by explants or cells derived from canine anterior cruciate, posterior cruciate, medial collateral, lateral collateral, or patellar ligaments. Taken together, these results indicate that chondrocytes represent the major source of inducible nitric oxide synthase and nitric oxide during inflammation or infection of a joint. | |
| 9437637 | Rheumatoid arthritis: current clinical and research directions. | 1997 Dec | Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and joint erosions. It affects approximately 1% of the adult population in a female/male ratio ranging from 2:1 to 4:1. RA is an insidious disease, typically having an onset of symmetric joint swelling and reaching a peak incidence in the fourth and fifth decades. Extraarticular manifestations include pulmonary, ocular, and vascular disease. The etiology of RA remains unknown. Attempts to discover infectious causes have proven unsuccessful, although environmental influences may trigger a response leading to the development of this autoimmune disease. Genetic associations have been identified, particularly with the major histocompatibility complex class II antigens. Furthermore, twin studies have shown a 30%-50% concordance rate for monozygotic twins. Approximately 70%-80% of patients with RA have rheumatoid factor present in the blood, although its role remains unclear. Hormonal status may influence RA. The majority of RA patients are women, and in 75% of them, the disease improves during pregnancy. RA has significant financial and social implications associated with treatment costs, lost wages, disability, and increased mortality. Mainstays of medical therapy have included nonsteroidal anti-inflammatory and immunosuppressive agents, such as prednisone and methotrexate. Recent advances in the treatment of RA include specific inhibitors of cyclooxygenase II, T cells, blood vessels, cytokines (such as tumor necrosis factor-alpha [TNF-alpha] or interleukin-1 [IL-1]), and adhesion molecules. Additional studies are ongoing with combination interventions. It is anticipated that a better understanding of the basic pathophysiologic mechanisms critical in RA pathogenesis will provide more precise and efficacious therapy. | |
| 11409156 | Treating early rheumatoid arthritis in the younger patient. | 2001 Jun | Early diagnosis and intervention may provide the greatest hope for reducing the disability associated with rheumatoid arthritis (RA). In patients with early RA, accurate diagnosis can be delayed by limited access to a specialist service, slow evolution of the clinical features, and lack of definitive diagnostic criteria. However, acute phase reactants, serologic features including presence of rheumatoid factor, and immunohistologic analysis of synovial tissue can provide the basis for differentiating RA from other forms of arthritis. Factors associated with poorer prognosis in patients with early RA are female sex, larger number of joints involved, elevated levels of acute phase reactants, presence of rheumatoid factor, and radiologic evidence of joint damage. Special treatment considerations in younger persons with RA include issues related to conception, pregnancy, and lactation. Methotrexate, hydroxychloroquine, sulfasalazine, and low dose corticosteroids are usually the mainstays of treatment for younger patients with RA. Recommendations for taking these drugs while considering conception vary with their effect on fertility and on the developing embryo. Sulfasalazine, for example, can be taken during pregnancy but caution is advised for breastfeeding mothers. Leflunomide must be discontinued for 2 years before attempting conception; this time can be shortened if the patient opts for drug washout. | |
| 10777119 | New treatment possibilities in rheumatoid arthritis. | 2000 | It is very difficult to predict future treatment modalities especially in diseases like rheumatoid arthritis (RA) with unknown etiology and pathogenesis. In the near future, traditional disease-modifying antirheumatic drugs (DMARD) alone, in combination with each other, or together with cyclosporine, FK506, Rapamycin, or Leflunomide, will probably be the main treatment for RA. Currently biological anti-TNFalpha agents like humanized MAb and recombinant TNF-receptor constructs are now launched in the market. This therapy alone, or in combination with methotrexate is very effective in RA patients. There are, however, concerns over increase in serious infections. Autologous stem cell transplantation will probably be used in certain patient with serious autoimmune diseases. | |
| 9782796 | Rheumatoid arthritis. Early intervention can change outcomes. | 1998 Jul | Rheumatoid arthritis (RA) is an autoimmune disease with a predilection for synovial tissues, although it can affect other organs. Although the precise etiology is uncertain, viruses, genetics, immune dysfunction and physical trauma have all been implicated as causes for RA. The most basic definition, therefore, is that RA is inflammatory. The RA patient may have difficulty closing a fist or may have a week grip. The late stages of RA are easy to identify by X-ray, but to really perform a service for a patient, you must be able to identify its early stages. To do this, you must be able to examine joints. If a patient does not have a history of liver disease or heavy alcohol intake, methotrexate is the first treatment choice except in the very mildest of cases, when you can use NSAIDs. Steroids are sometimes an essential treatment, but use them with great caution and pay attention to the minimum effective dose. | |
| 9266138 | Effects of cyclosporin on joint damage in rheumatoid arthritis. The Italian Rheumatologist | 1997 May | According to the most recent literature, few antirheumatic drugs can claim disease-controlling properties over the anatomical joint damage in rheumatoid arthritis (RA). A small number of studies have favored one or another of the available agents, in particular parenteral gold salts, sulphasalazine and methotrexate, but the evidence regarding their efficacy is not convincing when analysed using methodological criteria known to be important in evaluating radiologic evidence of joint damage. The radiologic results in long-standing RA patients have shown that CsA may be of benefit in reducing disease progression. Data from the second year of a clinical trial designed to compare the disease-controlling, anti-rheumatic properties of CsA with those of conventional disease-modifying anti-rheumatic drugs (DMARDs) in early RA support the hypothesis that CsA may be useful in delaying the appearance of new joint erosion. | |
| 11177770 | Radiography of rheumatoid arthritis in the time of increasing drug effectiveness. | 2001 Feb | Recent clinical development programs for new therapeutic agents in rheumatoid arthritis have included assessment of radiographic progression comparing changes with treatment to placebo and active controls. Studies now use reliable methods of assessment and sufficient study length to detect radiographic changes. Although patient populations and characteristics differ, and radiographic scoring methods vary, the direction of a series of studies appears to indicate that leflunomide (LEF), methotrexate (MTX), sulfasalazine (SSZ), etanercept, infliximab, and IL-1ra are all effective in retarding radiographic progression, as measured by erosions and joint space narrowing. Interpretation of radiograph data in future trials will be aided by utilization of common reading methods and by continuing comparison across differing rheumatoid arthritis protocol populations. | |
| 10529149 | Two cases of methotrexate induced lymphomas in rheumatoid arthritis: an association with i | 1999 Oct | We describe 2 patients with rheumatoid arthritis (RA) in whom non-Hodgkin's lymphomas developed during low dose pulsed methotrexate (MTX) treatment. The tumors regressed after discontinuation of MTX with no additional treatment. Serum levels of IgE increased concomitantly with the development of lymphoma, and decreased along with the regression of the lymphoma in both patients. These 2 cases and a review of the literature suggest that measuring serum IgE may have a predictive value for monitoring lymphoma in patients with RA treated with MTX. | |
| 9266137 | Adverse drug reactions of DMARDs and DC-ARTs in rheumatoid arthritis. | 1997 May | Comprehensive meta-analyses have revealed that survival on DMARD therapy in rheumatoid arthritis can be classified according to several factors: the number of adverse drug reactions, the percentage of drop-outs, and the duration of usage, which is clearly linked to both drug efficacy and drug toxicity. When taking into account of all of these issues, the impact of each DMARD can be scored differently, but certainly the length of time on a given DMARD gives us a conclusive, clinically important overview of its overall efficacy and safety. On these grounds, studies lasting two years or more have demonstrated that, while sulphasalazine can be employed for a median length of 12 months, methotrexate treatment can be maintained for more than 5 consecutive years. Severe and life-threatening complications have been observed with all conventional DMARDs. | |
| 10821370 | Methotrexate effects in patients with rheumatoid arthritis with cardiovascular comorbidity | 2000 May 6 | Methotrexate, an antirheumatic drug that may increase serum homocysteine, significantly increases mortality in patients with rheumatoid arthritis and cardiovascular comorbidity. | |
| 11212176 | Responsiveness of the self-assessed rheumatoid arthritis disease activity index to a flare | 2001 Jan | OBJECTIVE: To assess the responsiveness of the Rheumatoid Arthritis Disease Activity Index (RADAI) to increases in disease activity, using the occurrence of a flare of disease activity as an external standard. METHODS: A post hoc analysis was performed on data from a randomized, double-blind, controlled trial of methotrexate versus type II collagen in 92 patients with rheumatoid arthritis (RA). Responsiveness was analyzed by 1) correlating change in the RADAI score with change in the Disease Activity Score (DAS28), 2) determining the RADAI's ability to detect a disease flare by plotting a receiver operating characteristic (ROC) curve, and 3) using a responsiveness statistic, the standardized effect size (SES). The contribution of the single RADAI items to the change in total RADAI score was analyzed by the item score change in absolute value, the item responsiveness by the standardized response mean, and the correlation of item score change with total RADAI score change by Cronbach's alpha. RESULTS: Changes in the RADAI score correlated strongly with changes in the DAS28 (R2 = 0.70, P < 0.0001). The area under the ROC curve for the RADAI was 0.88 (95% confidence interval 0.78-0.95), which was similar to that for the DAS28. The SES for the RADAI was 1.56, which was also similar to that for the DAS28. The RADAI items of past global disease activity and morning stiffness contributed least to the total score change. CONCLUSION: This study provides evidence that the RADAI is sensitive to relevant increases in disease activity in RA patients. The RADAI may complement clinical measures in clinical studies, or may be used as a proxy for disease activity in epidemiologic studies. | |
| 9851273 | Progression in early erosive rheumatoid arthritis: 12 month results from a randomized cont | 1998 Nov | OBJECTIVE: To compare radiographic outcomes in patients with active early erosive rheumatoid arthritis (RA) who were treated with methotrexate (MTX) and gold sodium thiomalate (GSTM). METHODS: A total of 174 patients from two centres were randomly assigned to receive weekly i.m. injections for 12 months of either 15 mg MTX or 50 mg GSTM in a double-blind fashion. Radiographic evaluations including standardized scoring of 38 joints of the hands, wrists and forefeet, and count of eroded joints, were carried out at baseline and after 6 and 12 months in all patients, including withdrawals. RESULTS: An intention-to-treat analysis revealed no statistically significant difference in the progression of radiographic scores between treatment groups after 6 months (3.4 with MTX vs 2.6 with GSTM, P = 0.66) and after 12 months (6.0 vs 4.8, P = 0.44). A similar pattern was observed for the number of joints with erosions. The slope of radiographic progression was significantly reduced in the second half-year compared to the first 6 months in both groups. Erythrocyte sedimentation rate and C-reactive protein at baseline, and the presence of rheumatoid factor (RF), were the main predictors of progression in bivariate analysis. RF remained as the only predictor for radiographic outcome in multivariable analysis. CONCLUSION: In parallel to clinical improvement, both GSTM and MTX reduce the slope of radiographic progression in patients with active erosive RA. |