Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 11293246 | The effective of methotrexate on immune response cells in rheumatoid arthritis. | 2000 Nov | Methotrexate (MTX) is one of the most used medicines in rheumatoid arthritis [r. a.] treatment. There are many scientific reports which present influence of MTX on inflammatory process. In many centers influence of MTX on cytokines level have been investigated. Thanks to clinical studies it has been performed that MTX holds up activity and productions of Il-8, releasing of TNF-alpha and reduction of concentration Il-6. MTX holds up proliferation of monocytes, macrophages and synoviocytes. It has been indicated that MTX decreases synthesis of B-4 leucotrien in neutrophils, decreases level of neutral proteases, holds up cellular immunity and has antiproliferative influence on endothelial cells. There are reports, that MTX reduces expression of endothelial cells adhesive proteins and synthesis of chemotactic factors, stopping migration of leucocytes to tissues. | |
| 10589354 | Pharmacotherapeutic strategies for disease-modifying antirheumatic drug (DMARD) combinatio | 1999 Nov | OBJECTIVE: To provide a rational model for the use of disease-modifying antirheumatic drug (DMARD) combinations in the treatment of rheumatoid arthritis. METHODS: The DMARDs used today were examined for their mechanisms of action, kinetics, and toxicity, and collected into tabular formats for easier comparison. From these tables, matrices of potential positive or negative interfaces among combinations were constructed. Finally, these matrices were used to examine the usefulness of DMARD combinations by comparing them with published data. RESULTS: When clearly overlapping cells were found with respect to mechanisms of action, kinetics, or toxicity (e.g., methotrexate [MTX] plus azathioprine or MTX plus auranofin) predictions were good. When knowledge in these areas of kinetics and/or mechanisms of action were inadequate, predictions and results were not always consonant (e.g. MTX plus sulfasalazine; D-penicillamine plus hydroxychloroquine). CONCLUSIONS: The approach demonstrated in this paper toward rational combination therapy is logical and can be successful, although its success is circumscribed by our knowledge about the drugs we use. The rational approach to combination therapy demonstrated in this article can: 1) help prevent the use of combinations unlikely to be effective; 2) can point toward directions for useful research; and 3) can even be used when physicians are faced with patients whose needs have exceeded our present scientific knowledge. | |
| 11196542 | Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and p | 2001 Jan | OBJECTIVE: Rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS) are associated with an increased risk of lymphoma. Epstein-Barr virus (EBV), a ubiquitous herpes virus, has been linked etiologically to lymphoma in patients with RA and primary SS. Recently, methotrexate (MTX) has also been linked to the development of these lymphomas. We investigated the frequency of EBV in lymphoma tissue of patients with RA and primary SS and the association of MTX with lymphomagenesis. METHODS: Twenty-three patients with RA and 9 with primary SS with a history of lymphoma were identified by writing to all Arthritis Foundation member rheumatologists in Washington State. Formalin fixed, paraffin embedded tissue blocks were then requested from pathology laboratories. Lymph nodes from 5 RA patients without lymphoma were also studied. In situ hybridization using a biotinylated EBER-1 oligonucleotide probe was used to detect EBV in tissue sections. Positive and negative laboratory controls were used to ensure procedural integrity. RESULTS: Specimens from 21 RA patients were obtained, with 2 subsequently excluded due to specimen quality. Specimens from 6 patients with primary SS were obtained. In situ hybridization for EBV was positive in 5/19 (26%) RA patients and 1/6 patients with primary SS. In the nonmalignant lymph nodes no patient showed EBV. One primary SS and 12 RA patients were known to be taking MTX at the time of lymphoma diagnosis. Of the EBV positive RA lymphoma patients, 4/5 were receiving MTX at the time of diagnosis. These results show that EBV is present in lymphoma tissue of some patients with RA and very few with primary SS. CONCLUSION: EBV is over-represented in the lymphomas of patients with RA, but whether MTX plays a role in predisposing patients with RA and primary SS to the development of lymphoma, perhaps by influencing behavior of EBV, remains unclear. | |
| 11469521 | Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis | 2001 | The efficacy of weekly low-dose methotrexate treatment of rheumatoid arthritis is well documented. Efficacy and adverse effects are both dose dependent. and adverse effects rather than lack of efficacy are the main reason for discontinuing therapy. Several adverse effects are related to folate deficiencies, largely due to the antifolate properties of methotrexate. In order to reduce adverse effects without compromising drug efficacy, numerous clinical investigations have been performed using supplementation with folic or folinic acid during methotrexate therapy of patients with rheumatoid arthritis, addressing both the timing of folate supplementation and the weekly folate-to-methotrexate ratio. Based on these studies, an individually adjusted supply of folic acid rather than folinic acid is proposed. For many patients, however, a properly balanced diet is sufficient to avoid folate deficiency. | |
| 9651076 | Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion mo | 1998 May | Methotrexate (MTX) is one of the most widely prescribed drugs in the treatment of rheumatoid arthritis (RA). The mechanism by which MTX exerts its anti-rheumatic effect has not yet been defined. The aim of the present study was to investigate the effect of MTX treatment (7.5-15 mg/week) on synovial tissue in RA. For this purpose, synovial biopsies were taken from 11 RA patients before and 16 weeks after initiation of MTX therapy. Immunohistochemistry was performed using monoclonal antibodies (MAb) specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68, MAb67, Ki67, interferon gamma (IFN-gamma), interleukin (IL)-1alpha, IL-1beta, tumour necrosis factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All parameters for disease activity improved during the period of treatment. Immunohistochemical analysis revealed a statistically significant decrease in scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the adhesion molecules E-selectin and VCAM-1. The observed decrease in synovial scores for inflammatory cells, monokines and adhesion molecules suggests that the anti-inflammatory effect of MTX is, in part, dependent on a reduction in monokine-inducible vascular adhesion molecules and subsequent reduction of cell traffic into joints. | |
| 11060665 | IL-1 inhibitors: novel agents in the treatment of rheumatoid arthritis. | 2000 Jan | IL-1 is a pleiotropic cytokine shown to play a major role in synovitis and in the mechanisms that lead to the progressive joint destruction of rheumatoid arthritis (RA). IL-1 receptor antagonist (IL-1Ra), a member of the IL-1 family, binds IL-1 receptors but does not induce a cellular response. IL-1Ra competitively inhibits the binding of IL-1 to its cell surface receptors and thus acts as an endogenous anti-inflammatory mediator. In different experimental animal models of arthritis systemic administration of IL-1Ra, or local delivery into the joints by gene therapy attenuated the severity of the inflammatory response and reduced articular destruction. In addition, treatment of RA patients with IL-1Ra led to an improvement in different clinical and biological parameters and to a reduction in the radiological signs of joint erosions. Recently, interesting results were obtained using IL-1Ra in combination with methotrexate, a well-known antirheumatic drug, or in combination with other strategies designed to block the effects of tumour necrosis factor (TNF)-alpha. Encouraging results also have been reported in both in vitro and in vivo experimental models of arthritis by using other strategies designed to block the effects of IL-1. | |
| 10643695 | Response to methotrexate treatment is associated with reduced mortality in patients with s | 2000 Jan | OBJECTIVE: This study investigated whether efficacious methotrexate (MTX) treatment has an impact on mortality of patients with severe rheumatoid arthritis (RA). METHODS: In this prospective, observational, one-center study, patients with severe RA refractory to other disease-modifying antirheumatic drugs started MTX treatment between 1980 and 1987. Patients were divided into 4 different groups according to their response to MTX treatment after 1 year (>50% improvement [n = 99], 20-50% improvement [n = 70], no improvement [n = 52], and discontinued treatment [n = 35]). After a followup of 7.5-15.3 years (mean 10 years), the numbers of deaths were assessed in the different groups. Standardized mortality ratios (SMR) were calculated by comparing the number of observed deaths in the study with the number of expected deaths in an age- and sex-matched sample of the general population. RESULTS: Two hundred seventy-one patients entered the study between 1980 and 1987. In 1995/1996, outcomes for 256 patients (94.5%) could be documented; 88 patients (34.4%) had died. In patients with >50% improvement after 1 year, the SMR was 1.47, while in patients with 20-50% improvement, the SMR was 1.85. In both groups combined, the SMR was 1.64 (95% confidence interval [95% CI] 1.11-2.17), compared with 4.11 (95% CI 2.56-5.66) in patients without improvement. Patients who had discontinued MTX treatment during the first year had an SMR of 5.56 (95% CI 3.29-7.83). CONCLUSION: Patients with severe RA who do not respond to MTX treatment have a poor prognosis, with >4-fold increased mortality compared with the general population, while RA patients who respond to MTX treatment have only a moderately increased mortality rate. | |
| 9564773 | [The efficacy of combination therapy with prednisolone (PSL) and methotrexate (MTX) on rad | 1998 Feb | A case-controlled study was performed, based on early active RA patients treated with MTX; Prednisolone (PSL) was also given in sixteen patients (PSL + MTX group) and each of them was matched for age and sex with a control who have never received PSL (MTX group). No significant differences in radiographic progression were found between the 2 groups. Analysis of radiographic parameters showed that CRP, erythrocyte sedimentation rate, and titers of serum rheumatoid factors after 6 months treatment and their integral amounts during cource were significantly high in the patients with marked radiographic progression. There was no relationship between radiographic progression and treatment with PSL. These results suggested that the indication of PSL therapy for RA is limited for patients with the poor decrease in the level of CRP, erythrocyte sedimentation rate, and rheumatoid factor by MTX treatment. | |
| 9667614 | Combination therapy in rheumatoid arthritis: updated systematic review. | 1998 Jun | In a second update of a systematic review, many new developments in the combined drug treatment of rheumatoid arthritis (RA) are highlighted. In early RA patients, step-down bridge therapy that includes corticosteroids leads to much enhanced efficacy at acceptable or low toxicity. The effects on joint damage may be persistent, but the symptomatic effects are probably dependent on continued corticosteroid dosing. In late patients, cyclosporin improves a suboptimal clinical response to methotrexate, and the triple combination of methotrexate, sulphasalazine and hydroxychloroquine appears to be clinically better than the components. Other combinations are either untested, tested at low sample size, or show negative interaction. In view of the low volume of evidence, most studies need confirmation by replication. | |
| 9801709 | Cervical myelopathy due to rheumatoid arthritis. Case report and review of the literature. | 1998 Sep | We present the case report of a 62 year-old female suffering from destructive rheumatoid arthritis (RA) for more than 20 years. She had complaints of progressive gait impairment and numbness in hands and feet. Neurological examination showed an unstable gait and pyramidal tract signs. Anterior atlantoaxial subluxation with pannus formation and cervical myelopathy were demonstrated using conventional X-ray studies and MRI. She was conservatively treated with a soft collar. Treatment with methotrexate and an intensive gait revalidation program were started. RA commonly involves the cervical spine, usually in advanced systemic disease after a mean delay of 16 years. Subluxations of the cervical spine are found in 43 to 86%, 50% of these patients are asymptomatic. The reported rate of neurological impairment due to cervical instability ranges from 7 to 58%. The three most common lesions resulting from cervical RA are atlantoaxial subluxation (50 to 70%), subaxial subluxation (15 to 25%) and cranial settling (20%). It is important to differentiate between cranial settling and atlantoaxial instability, as the latter may have a more benign history with less than 20% showing progressive instability. Cranial settling progresses in 35 to 50% of patients. The commonest presenting features of rheumatoid cervical myelopathy are isolated sensory symptoms. Most patients were found to have multiple neurological deficits once the myelopathy was diagnosed. A mean delay of 31 weeks between the first symptom and the diagnosis of the myelopathy is reported. The sensory symptoms are often misinterpreted as being due to entrapment neuropathy or rheumatoid peripheral neuropathy. Radiographic analysis indicates that the posterior atlantoodontoid interval (< or = 14 mm) is an important parameter that shows excellent correlation with the severity of paralysis. | |
| 9213378 | Lymphoma in patients with rheumatoid arthritis: association with the disease state or meth | 1997 Jun | Although long-term clinical studies have shown no excessive risk of lymphoma in rheumatoid arthritis (RA) patients treated with methotrexate (MTX), an increasing number of reports of this association continue to appear. We describe two cases, review the cases in the world's literature, and summarize their important characteristics. Possible oncogenic mechanisms are discussed. Most lymphoproliferation cases presented here have features of immunosuppression-associated lymphoma. The immunosuppressed state is attributable to a combination of factors, such as RA itself and the actions of MTX. The risk factors for RA patients to develop lymphoma while on MTX include severe disease, intense immunosuppression, genetic predisposition, and an increased frequency of latent infection with prooncogenic viruses such as Epstein-Barr virus (EBV). The spontaneous remission of lymphomas in eight RA patients after MTX was stopped highlights the likely causative role of the drug in the development of these malignancies. If the clinical situation permits, a period of observation for spontaneous remission after MTX is stopped is advisable. The physicians caring for RA patients on MTX should maintain a high surveillance for signs and symptoms suggestive of lymphoma. | |
| 11254248 | Pancytopenia and colitis with Clostridium difficile in a rheumatoid arthritis patient taki | 2001 | Methotrexate (MTX) is widely used despite its side-effects. We describe a rheumatoid arthritis (RA) patient taking low-dose MTX who developed severe pancytopenia and colitis with Clostridium difficile after the administration of antibiotics for acute pyelonephritis. Our case suggests that low-dose MTX may seriously interact with antibiotics and that these side-effects should always be considered when RA patients are treated with MTX and antibiotics. | |
| 10609068 | Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthr | 1999 Nov | OBJECTIVE: The response to single disease modifying antirheumatic drug (DMARD) is often suboptimal in patients with rheumatoid arthritis (RA). Thus, despite the limited data on the therapeutic efficacy of combination therapies, many patients are currently treated with a combination of DMARDs. METHODS: We studied prospectively the efficacy of combination therapy with DMARDs. The study was designed as a randomized trial and a single DMARD or two or three DMARD combinations were administered to 180 consecutive, age- and sex-matched patients with active RA, each of whom was followed up for a period of 2 years under treatment. Patients were divided into 3 groups which did not differ with regard to demographic, clinical and laboratory parameters. Patients in group I were treated with a single DMARD [methotrexate (MTX) 7.5-15 mg/week or sulfasalazine (SSZ) 1-2 g/day or hydroxychloroquine (HCQ) 200 mg/day], group II with MTX + SSZ or MTX + HCQ, and group III with a combination of all three drugs. Patients were re-evaluated at regular intervals by means of clinical and biochemical tests designed to detect specific rheumatic activity. Radiological assessments were also performed and scored according to Larsen by the same radiologist who was blinded to the treatment groups. RESULTS: At the end of the trial there were significant improvements in the clinical and laboratory parameters in all 3 groups. However, improvements were greater and much more significant in the patients who were given combination therapies. The combination of MTX + SSZ + HCQ was more effective than both monotherapy and the two-drug combinations. CONCLUSION: In conclusion, we suggest that patients with RA should be treated with combinations of DMARDs. | |
| 9330927 | Long-term treatment of destructive rheumatoid arthritis with methotrexate. | 1997 Oct | OBJECTIVE: To evaluate the tolerability and efficacy of methotrexate (MTX) treatment in patients with longstanding, progressive, active rheumatoid arthritis (RA) who had failed one or more disease modifying antirheumatic drugs (DMARD). METHODS: Two hundred seventy-one consecutive patients with RA in whom MTX treatment was introduced were followed at regular intervals for up to 108 months. Evaluations included the number of swollen joints, grip strength, patient assessment of pain and mobility, erythrocyte sedimentation rate (ESR), and hemoglobin. Radiographs of hands and feet were taken once a year and 32 joints were evaluated according to a modified Larsen score. RESULTS: Of the 271 patients, 269 had prior treatment with one DMARD, primarily parenteral gold, and 58% with 2 or more DMARD. MTX was started parenterally in all patients in doses between 15 and 25 mg weekly and continued by oral medication in most of the cases. Eighty-three percent of patients complained of adverse events. The most common side effects were nausea, hair loss, transaminase increase, and stomatitis. In 45 patients (16.5%), MTX was withdrawn because of side effects, mostly during the first year. Sixteen patients (5.9%) died during followup, mainly due to myocardial infarction, heart failure, stroke, or cancer. After one year, 78.7% and after 5 years 60.3% of the patients were still taking MTX. Number of swollen joints, ESR, grip strength, patient assessment of pain, and mobility improved significantly at all measurement points. Improvement in the swollen joint count and the ESR of over 50% was seen in more than 50% of patients. Inactivation of the disease, defined as < 2 swollen joints, ESR < 20 mm, and no concomitant steroid use, occurred in 8-14% of patients. Steroid intake was significantly reduced. In spite of clinical improvement the modified Larsen score showed a progression in the vast majority of patients. CONCLUSION: Even in patients with longstanding, active, destructive RA who failed one or more DMARD, MTX treatment is well tolerated and improves clinical and biochemical disease activity significantly, while radiographic progression is still present. | |
| 9621475 | Efficacy of methotrexate in rheumatoid arthritis. | 1997 Dec | Rheumatoid arthritis is a common inflammatory articular disorder in Bangladesh. Methotrexate has proved to be an effective and relatively safe disease modifying drug for this disease. A quasiexperimental trial of the efficacy of methotrexate in rheumatoid arthritis was carried out in the Rheumatology Clinic, Institute of Postgraduate Medicine & Research, Dhaka during the period between July 1992 and September 1993. Thirty eight patients fulfilling the revised ARA criteria were given methotrexate in a total weekly dose of 7.5 to 15 mg. They were followed up at weekly intervals for one month and then monthly for a total duration of six months. Twenty three subjects eventually completed the trial. The trial showed significant differences in the disease activity indices at the end of six months. The decline of activity was noted at the end of one month. As a whole the response was complete in 4(17%), marked in 14(61%), moderate in 4(17%) and nil in 1(4%). Adverse effects occurred in 27 subjects. They were mild and transient in 22. Methotrexate appeared to be an acceptable DMARD for our rheumatoid arthritis population. | |
| 10353096 | Quantitative changes in peripheral blood lymphocytes in erosive rheumatoid arthritis patie | 1999 Mar | In order to better understand the immunological mechanisms involved in the pathogenesis of rheumatoid arthritis (RA), the level of various lymphocyte subsets in the peripheral blood of 29 patients with erosive RA was determined. All the patients were treated with methotrexate for 2 years. The total number and the proportion of CD3 cells, CD3+CD4+ and CD3+CD8+ cells did not change during the study. The initially increased level of CD19+ B-cells and CD19+CD5+ cells decreased during the treatment. The percentage of CD3-CD16+ natural killer cells was not affected by the treatment. At the inception of the study, we observed a deficiency of CD4+ CD45RA+ cells and the level of CD3+CD29+ cells was slightly increased. During the treatment we noticed significant elevation of CD45RA cells. Consequently, the CD29/CD45RA ratio significantly decreased. We showed significant correlation between changes in disease activity and changes in the level of CD19+ cells and CD4+CD29+ cells. Our results suggest that low-dose methotrexate may affect immunocompetent cells. The lowering in the CD29+ subset population associated with depletion of CD19 B-cells after methotrexate therapy may limit abnormal CD4+ cell activation and reduce the migration of lymphocytes into inflamed synovium. | |
| 10728742 | Clinical improvement as reflected in measures of function and health-related quality of li | 2000 Mar | OBJECTIVE: To examine correlations between clinical improvement as defined by the American College of Rheumatology (ACR) responder analysis and clinical improvement as determined by 4 function and/or health-related quality of life measures, and to estimate the sensitivity and relative efficiency of these measures compared with changes in the tender joint count in patients with rheumatoid arthritis (RA). METHODS: A 52-week, multicenter, double-blind controlled trial was conducted to compare treatment with leflunomide (n = 182), methotrexate (n = 180), or placebo (n = 118) in patients with active RA. ACR response rates and improvement in scores on the Health Assessment Questionnaire (HAQ), Problem Elicitation Technique (PET), and Medical Outcomes Survey Short Form 36 (SF-36) were compared in 438 of the patients. RESULTS: In comparing leflunomide with placebo, the patient global assessment, HAQ disability index, and SF-36 bodily pain scale were most responsive to treatment group differences. The modified HAQ (M-HAQ), PET Top 5, SF-36 physical component score, physician global assessment, pain intensity scale, and SF-36 physical functioning scale were more responsive to treatment group differences than was the tender joint count. In comparing methotrexate with placebo, the patient and physician global assessments were most responsive. These 2 measures, as well as the pain intensity scale and the C-reactive protein level, were more responsive to treatment group differences than was the tender joint count, while the SF-36 mental health component score was least responsive. A close correlation between changes in the M-HAQ and HAQ scores indicated that the M-HAQ was similarly responsive to change over time. Improvements in the PET, SF-36 physical component score, bodily pain, and physical functioning scales correlated with the ACR responder status. CONCLUSION: Both disease-specific and generic measures of function and health-related quality of life detect improvements in RA patients. Using both types of measures for evaluating therapies will identify discernible changes that are important to patients, and will facilitate comparisons across different disease states. | |
| 10852985 | Methotrexate as a preferential cyclooxygenase 2 inhibitor in whole blood of patients with | 2000 May | OBJECTIVE: To investigate the regulation of whole-blood cyclooxygenase-1 and -2 (COX-2 and COX-1) activities by methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: Whole blood was withdrawn from nine healthy volunteers, 12 RA patients treated with MTX (RA/MTX) and six RA patients treated with chloroquine (RA/CQ). COX-1 activity was quantified as platelet thromboxane B(2) production in unstimulated blood and COX-2 activity was measured as prostaglandin E(2) (PGE(2)) production in whole blood stimulated with LPS. Thromboxane B(2) and PGE(2) were measured by radioimmunoassay. We studied the drug effect in vitro by direct incubation of MTX with blood obtained from normal donors. Ex vivo assays were performed with blood collected from RA/MTX and RA/CQ patients. The influence of serum factors on enzyme activities was analysed in blood collected from normal donors and incubated with RA/MTX, autologous or heterologous serum. RESULTS: In vitro assays showed no direct action of MTX on the activity of either enzyme. Assays performed with blood from RA/MTX patients showed preferential inhibition of COX-2 activity (PGE(2) = 10.11 +/- 2.42 ng/ml) when compared with blood of normal donors (PGE(2) = 37.7 +/- 4.36 ng/ml; P = 0.001). Inhibition of COX-2 activity was also observed when blood of normal donors was co-incubated with RA/MTX serum. CONCLUSION: Our results clearly show that the anti-inflammatory action of low-dose MTX is partly mediated by a serum factor induced by MTX or a MTX metabolite that preferentially inhibits the activity of COX-2. | |
| 9858446 | Diagnostic confusion caused by hepatitis C: hemochromatosis presenting as rheumatoid arthr | 1998 Dec | We describe a patient with hemochromatosis and coexistent infection with the hepatitis C virus who was initially thought to have rheumatoid arthritis. His symptoms began at the age of 44 with pain of the hand joints, shoulders, hips, and knees and a positive rheumatoid factor. Four years later, he required replacement of both hips due to severe hip arthritis. Abnormalities in liver function were noted early on, but they were attributed to infection with the hepatitis C virus, detected serologically and by polymerase chain reaction amplification in the blood. The correct diagnosis was delayed until a decision to use methotrexate as treatment for his arthritis led to a liver biopsy, which revealed increased iron deposition consistent with hemochromatosis, confirmed by genetic testing, which revealed that the patient was homozygous for the C282Y mutation of the HLA-H gene. | |
| 9920948 | A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in | 1999 Jan 28 | BACKGROUND: Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease. This study was undertaken to determine whether the addition of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein (TNFR:Fc), to methotrexate therapy would provide additional benefit to patients who had persistent rheumatoid arthritis despite receiving methotrexate. METHODS: In a 24-week, double-blind trial, we randomly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week (or as low as 10 mg per week for patients unable to tolerate higher doses) to receive either etanercept (25 mg) or placebo subcutaneously twice weekly while continuing to receive methotrexate. The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity (ACR 20) at 24 weeks. RESULTS: The addition of etanercept to methotrexate therapy resulted in rapid and sustained improvement. At 24 weeks, 71 percent of the patients receiving etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria (P<0.001); 39 percent of the patients receiving etanercept plus methotrexate and 3 percent of those receiving placebo plus methotrexate met the ACR 50 criteria (for a 50 percent improvement) (P<0.001). Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity. The only adverse events associated with etanercept were mild injection-site reactions, and no patient withdrew from the study because of adverse events associated with etanercept. CONCLUSIONS: In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone. |