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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16633927 | Efficacy and safety of bucillamine, a D-penicillamine analogue, in patients with active rh | 2006 | Japanese rheumatologists consider bucillamine (Buc) to be a useful disease-modifying antirheumatic drug (DMARD) and often give Buc to patients with rheumatoid arthritis (RA) prior to administering methotrexate (MTX). However, no large studies on the efficacy and safety of Buc in RA patients have been published in English to date. We therefore investigated the clinical course of RA patients treated with Buc and compared the results with those for patients treated with MTX to evaluate and confirm the place of Buc in therapeutic strategies for RA in Japan. Our results suggested that Buc should be given to patients with moderately active RA either before or after the administration of MTX because its efficacy can be judged within 3 months and because serious adverse events are rare. Issues like the ability of Buc to prevent joint destruction and its efficacy and safety when combined with agents like etanercept require future study. | |
16905578 | Methotrexate pharmacogenomics. | 2006 Sep | Observations of clinical effects of methotrexate will help in patientâ€management decisions | |
18613827 | Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutic | 2008 Jun | Advances in cDNA and monoclonal antibody technology in the 1980s fuelled the discovery and characterization of the properties of cytokines. It became apparent that because cytokines were expressed in tissues derived from autoimmune diseases, they were likely to be of fundamental importance in disease pathogenesis and developing a new class of biological therapeutics. In this review, we describe the history of bench to bedside translation of work that led to the identification of tumor necrosis factor (TNF) as a key regulator of the loss of homeostatic immune-inflammatory responses in rheumatoid arthritis (RA) and a good therapeutic target. First in human clinical trials in collaboration with a biotechnology company, the safety and efficacy of TNF blockade with a chimeric monoclonal antibody was substantiated in patients refractory to standard anti-rheumatoid drugs. Abnormal immune-inflammatory responses after therapy showed improvement and remain a focus of ongoing research in many laboratories. Longer term multi-center studies that followed with several anti-TNF biologicals have demonstrated the augmented efficacy, including inducing clinical remission, of low dose methotrexate and anti-TNF therapy co-therapy, but serious infections and lymphomas in a low frequency have been observed. In the course of the past decades, three 'blockbuster' anti-TNF biologicals are in the clinic. Over a million patients with RA and other immune-mediated diseases have been successfully treated, and a better perspective on the risk of harm and its management has become part of good clinical practice. This success has encouraged a burgeoning industry of biologicals for chronic diseases. | |
17764060 | Pulmonary manifestations of rheumatoid arthritis. | 2007 Aug | Rheumatoid arthritis (RA) is a systemic disease, characterized by symmetric joint involvement, but it can also affect other organ systems, including the lungs. The better-known pulmonary manifestations of RA are interstitial lung disease, rheumatoid nodules, and pleural effusions. Less common manifestations include bronchiolitis obliterans and crycoarytenoid arthritis. Management of these conditions involves, by and large, supportive pulmonary care and control of the underlying articular process. Other pulmonary manifestations in RA patients can ensue as a result of the treatments used for it, mainly methotrexate. This article discusses the most common pulmonary manifestations of RA and their treatment. A discussion about the increasing impact that cigarette smoking is having on RA is also provided. | |
18274813 | Are Thymidylate synthase and Methylene tetrahydrofolate reductase genes linked with methot | 2008 Jun | Methotrexate (MTX) is among the best-tolerated disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis (RA); major drawbacks of MTX therapy are the large interpatient variability in clinical response and the unpredictable appearance of a large spectrum of side effects. Several studies have demonstrated gene polymorphism that may regulate intracellular methotrexate metabolic pathway enzymes linked to drug efficacy and safety, but the evidence available is not yet conclusive. We decided to run a pilot study to determine the incidence of Methylene tetrahydrofolate (MTHFR; C677T, A1298C) and Thymidylate synthase (TS; 5' UTR repeat, 3' UTR deletion) gene polymorphism in rheumatoid arthritis patients in our community (Indian Asian) and further explore its association with MTX response (efficacy, toxicity). Thirty-four naïve RA patients on supervised MTX therapy and 139 healthy controls were genotyped for A1298C and C677T polymorphism of the MTHFR gene and 5' UTR repeat and 3' UTR deletion polymorphism of the TYMS gene by polymerase chain reaction-restriction fragment length polymorphism. Association, if any, between gene polymorphism and MTX response in RA patients was analyzed. The MTHFR A1298C 'C' allele incidence among RA patients (46%) was significantly higher (chi2 = 4.24, P < 0.05, OR = 1.68). None of the other allele tested showed any association. Although a small sample study, our findings do not suggest a significant association of MTHFR/TS allele/genotype with MTX response in our ethnically distinct Indian (Asian) RA patients. | |
18766127 | Effects of methotrexate use in a patient with rheumatoid arthritis and multiple sclerosis. | 2008 Aug | Rheumatoid arthritis (RA) and multiple sclerosis (MS) share similar pathophysiologic processes but coexistence of both diseases in the same patient has rarely been described. We describe the case of a 32 year old woman with rheumatoid arthritis treated with 12.5 mg of methotrexate once a week and 1 mg folic acid who developed paresthesias of her upper and lower extremities. Three years later, she acutely developed 6th nerve palsy, gait imbalance and urinary urgency and a diagnosis of multiple sclerosis was made. The use of methotrexate, though effective in controlling her rheumatoid arthritis, did not influence the development or progression of her multiple sclerosis. Although RA and MS may coexist in the same patient, treatment of one disease may have no influence on the clinical course of the other. Thus, the mechanism by which methotrexate suppresses disease activity in RA but not in MS despite both being T-cell mediated autoimmune diseases requires further investigative studies. | |
17021669 | Influence of intraarticular corticosteroid administration on serum cytokines in rheumatoid | 2007 May | Though the efficacy of intraarticular (IA) corticosteroid administration in the therapeutic management of rheumatoid arthritis (RA) has been well documented, its immunomodulatory effects have not been defined. Categorization of these effects is important to develop safe derivative therapeutic strategies with a more targeted mechanism of action as they relate to the pathophysiology of RA. We describe here a broad spectrum immune response to inflammation as evidenced by rapid transient systemic inhibitory effects on key inflammatory regulators induced by the effects of IA administration of triamcinolone acetonide in a case of active RA who failed to respond to methotrexate. | |
18843784 | Circulating dickkopf-1 and radiological progression in patients with early rheumatoid arth | 2008 Dec | OBJECTIVE: Dickkopf-1 (Dkk-1) regulates bone remodeling in animal models of inflammatory arthritis, but its role in patients with rheumatoid arthritis (RA) remains unclear. METHODS: Baseline circulating Dkk-1 was measured in 113 patients with RA (< 3 yrs) who received etanercept (10 or 25 mg twice/week, n = 63) or methotrexate alone (n = 40) for 1 year. Progression was assessed by changes in radiological Sharp score. RESULTS: Increased Dkk-1 was associated with a higher risk of progression of bone erosion, independently of age, sex, baseline radiological damage, C-reactive protein, and disease activity in patients treated with etanercept. CONCLUSION: Dkk-1 may be an important mediator of bone erosion in patients with RA. | |
17544962 | Rheumatoid nodule. | 2007 Jun | Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis. Dermatologist may be concerned with the diagnosis and management of rheumatoid nodules, although most patients will probably be under the care of a rheumatologist. This article focuses in clinical, pathogenic, diagnostic, and therapeutic aspects of rheumatoid nodules. Classic rheumatoid nodules commonly occur in genetically predisposed patients with severe, seropositive arthritis. However, they may appear in other clinical settings. Accelerated rheumatoid nodulosis, especially involving the hands, has been reported in patients receiving methotrexate, antitumor necrosis factor alpha biologic drugs or leflunomide therapy for rheumatoid arthritis. Rheumatoid nodulosis is characterized by multiple rheumatoid nodules, recurrent joint symptoms with minimal clinical or radiologic involvement, and a benign clinical course. Pseudorheumatoid nodules have been reported in healthy children. Although histologically almost indistinguishable from true rheumatoid nodules, some consider these lesions to be a form of deep granuloma annulare. | |
16447237 | The LUNDEX, a new index of drug efficacy in clinical practice: results of a five-year obse | 2006 Feb | OBJECTIVE: To describe the use of the LUNDEX, a new index for comparing the long-term efficacy and tolerability of biologic therapies in rheumatoid arthritis (RA) patients treated in clinical practice. METHODS: Patients (n = 949) with active RA that had not responded to at least 2 disease-modifying antirheumatic drugs (DMARDs) including methotrexate, in whom biologic therapy was being initiated, were included in a structured clinical followup protocol. The protocol included collection of data on diagnosis, disease duration, previous and ongoing DMARD treatment, and dates on which biologic treatment was started and terminated. In addition, data on efficacy measures used for calculating validated response criteria, i.e., the European League Against Rheumatism and American College of Rheumatology response criteria, were collected at fixed time points. Data were prospectively registered from March 1999 through January 2004. The LUNDEX, a new index combining the proportion of patients fulfilling a selected response criteria set with the proportion of patients adhering to a particular therapy, was designed to compare the efficacy of the different therapies. RESULTS: Etanercept had higher overall LUNDEX values compared with infliximab, mostly because of a lower rate of adherence to therapy with infliximab. The relationship between the drugs was consistent irrespective of the response criteria used. CONCLUSION: The LUNDEX is a valuable tool for evaluating drug efficacy in observational studies. It has the advantage of integrating clinical response as well as adherence to therapy in a composite value. Moreover, the LUNDEX has a practical and potentially universal application independent of diagnosis and response criteria. | |
17977487 | Quality of life in patients with rheumatoid arthritis: does abatacept make a difference? | 2007 Sep | Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease that, in addition to causing joint damage, is associated with pain, fatigue, disability and functional loss, which can substantially decrease a patient's quality of life (QoL). Along with improvements in signs and symptoms, QoL benefits have become increasingly important in optimizing treatment outcomes in RA. Measurements of QoL have previously been under-used in all areas of medicine and only recently have clinical trials included them as a measure of treatment effectiveness. The existence of a positive relationship between improvements in signs and symptoms and concomitant improvements in QoL provides additional evidence that QoL measures are useful benchmarks for evaluating the effectiveness of treatment for RA. Furthermore, since these outcome measures evaluate the real-life, patient-centered benefits of RA therapies, they are likely to become increasingly central to the assessment of disease impact in clinical trials and practice, and to both drug approval and reimbursement decisions. This article reviews the impact of abatacept, a selective co-stimulation modulator, on the QoL of patients with active RA across a number of pivotal clinical trials. Firstly, an overview of the key QoL measurements used in abatacept clinical trials is provided, including those such as the Short Form-36, Health Assessment Questionnaire and Visual Analog Scale for pain, sleep and fatigue. We then present QoL data obtained in a wide range of patients with RA, including those with an inadequate response to either methotrexate or anti-tumor necrosis factor therapy, who have been treated with abatacept. Analysis of these data demonstrates that abatacept therapy has the potential to improve QoL across a range of patients with RA. | |
17714062 | The use of TNF-alpha blocking agents in rheumatoid arthritis: an update. | 2007 Sep | TNF-alpha has been found to play a pivotal role in the pathogenic mechanisms of rheumatoid arthritis (RA). Drugs targeting TNF-alpha have been developed to neutralise the deleterious effects of this inflammatory cytokine. There are, at present, three drugs available for the treatment of RA patients with active disease who are refractory to conventional treatments including methotrexate: 2 monoclonal antibodies, infliximab and adalimumab, and a fusion protein with p75 receptors, etanercept. These three agents have proved to be effective and safe in large placebo-controlled trials enrolling patients with established or early disease and showed effectiveness in controlling signs and symptoms of the disease, improving quality of life and in slowing and even arresting the progression of radiographic damage. With the long-term surveillance of these drugs were described serious adverse events, particularly infections such as tuberculosis, especially with infliximab. The risk for malignancies under TNF-alpha antagonists, especially lymphoma, remains controversial. Specific recommendations are given by international experts for selecting and monitoring RA patients with TNF-alpha antagonists. Other drugs targeting TNF-alpha such as PEGylated molecules (CDP870 or certolizumab) are in development. These new biological therapies blocking TNF-alpha undoubtedly constitute a considerable advancement in the management of RA, but careful evaluation at the initiation of the treatment and long-term surveillance of the patients receiving such drugs remains necessary. | |
17586865 | The pharmacogenetics of methotrexate. | 2007 Oct | Methotrexate (MTX) is a cornerstone of therapy for rheumatoid arthritis. However, it is not universally effective and up to one-third of patients fail to respond to treatment, either because of inefficacy or adverse events, although at present it is not possible to predict therapy response accurately. Pharmacogenetics is the study of variability in drug response due to heredity. MTX has a complex intracellular metabolism and acts via a number of key enzymes. This review critically appraises the studies of MTX pharmacogenetics and highlights the need for further work in this area. | |
17896806 | Bone mineral density in older adult patients with rheumatoid arthritis: an analysis of NHA | 2007 Oct | OBJECTIVE: Several studies suggest that bone mineral density (BMD) is reduced in rheumatoid arthritis (RA). However, it is unclear whether this relationship holds in a representative community-based typical RA population. We examined the relationship between BMD and RA in a representative US population-based sample from the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994). METHODS: We selected subjects over age 60 with RA from NHANES III using previously described methods. Femoral neck BMD (FN-BMD) measured by dual-energy x-ray absorptiometry was compared for the RA (n = 106) and non-RA cohorts (n = 4,277). Multivariable linear regression models included known risk factors for osteoporosis. Further adjusted analyses compared the BMD among subgroups of patients with RA, such as those taking methotrexate (MTX), those with positive rheumatoid factor (RF), and those with elevated C-reactive protein (CRP). RESULTS: Patients with RA more frequently reported poor health, a history of falling, cognitive impairment, early menopause, a history of chronic obstructive lung disease, higher total calcium intake, and thiazide use than the non-RA subjects (all p < 0.05). Adjusted FN-BMD was similar between the patients with RA (0.71 g/cm2) and non-RA subjects (0.72 g/cm2; p = 0.5). Among patients with RA, reduced BMD tended to be seen with MTX use (0.60 g/cm2, p = 0.07), CRP above 1 mg/dl (0.66 g/cm2, p = 0.09), and positive RF in female patients (0.68 g/cm2, p = 0.056). However, none of these findings reached statistical significance. CONCLUSIONS: Among a US population-based representative sample, FN-BMD was similar in RA and non-RA patients. Several characteristics of patients with RA may be associated with reduced BMD. | |
17927490 | Abatacept: a novel treatment for rheumatoid arthritis. | 2007 Oct | Rheumatoid arthritis (RA) is a chronic, autoimmune disease that has traditionally been treated with non-biologic and biologic disease-modifying antirheumatic drugs (DMARDs). Although these agents have become firmly established as effective RA treatments, some patients do not have an adequate response. The recent approval of abatacept, a first-in-class agent that selectively modulates the activation of T cells, offers an alternative therapeutic option. As reflected in pharmacokinetic analyses, abatacept 10 mg/kg has been shown to be effective in treating patients with established RA. Demonstrating safety, efficacy and quality of life improvements in a wide range of RA patients, including those with inadequate response to methotrexate or tumor necrosis factor antagonists, abatacept is seen as a valuable addition to the RA treatment armamentarium. | |
18301411 | Safe adalimumab therapy for rheumatoid arthritis in a patient with pre-existing multiple m | 2008 Apr | BACKGROUND: We report on a patient with rheumatoid arthritis (RA) who was treated with adalimumab and retrospectively diagnosed as having a multiple myeloma. INVESTIGATIONS: In addition to the determination of clinical symptoms, investigations included radiography of the thorax, spine, hands and feet, arthrosonography, determination of laboratory parameters (including C-reactive protein levels and presence of antibodies against cyclic citrullinated peptide), cytogenetics and electrocardiography. DIAGNOSIS: RA was initially diagnosed in 1988. Stage II and stage III RA were diagnosed for the left and right foot, respectively, in 1996. Joints of both hands were diagnosed with stage I RA; both wrists and some finger joints showed signs of synovitis. Plasmocytoma was diagnosed in 2004; however, investigation of medical records revealed evidence of multiple myeloma 8 years earlier, in 1996. MANAGEMENT: RA was originally treated with gold, sulfasalazine, azathioprin and glucocorticoid. Methotrexate was later used in addition to cortisone and then in combination with a selective cyclo-oxygenase-2 inhibitor. A combination therapy consisting of adalimumab (40 mg every 2 weeks), methotrexate (15 mg weekly) and a cyclo-oxygenase-2 inhibitor (rofecoxib 25 mg daily until July 2004, etoricoxib 90 mg daily from October 2004) was started in November 2003. Adalimumab therapy was interrupted for 6 months owing to safety concerns, but was resumed after a careful risk-benefit assessment. | |
18084706 | Gynecomastia associated with low-dose methotrexate therapy for rheumatoid arthritis. | 2007 | A 68-year-old man with a 3-year history of rheumatoid arthritis (RA) developed gynecomastia 3 months after beginning oral low-dose methotrexate (MTX) therapy. Four months after MTX therapy was discontinued, the gynecomastia symptoms improved. Only eight cases of gynecomastia resulting from low-dose MTX administration have been reported worldwide, and no cases have previously been reported in Japan. Although it occurs infrequently, gynecomastia resulting from low-dose MTX therapy should be considered in male patients with RA. | |
18357499 | Characteristics and medical management of patients with rheumatoid arthritis and ankylosin | 2008 Sep | Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, progressive, systemic inflammatory rheumatic diseases that lead to serious disability. The objective of this study was to investigate the demographic and clinical characteristics of the patients with RA and AS who were treated in tertiary hospitals in Turkey and to analyze their current medical management. A total of 562 RA and 216 AS patients were evaluated. The mean age of RA patients was 52.1 +/- 12.6 years. The female to male ratio was 3.7:1. Of the RA patients, 72.2% had positive rheumatoid factor (RF), 62.9% had high C-reactive protein, and 75.2% had radiological erosion. The ratio of patients with Disease Activity Score (DAS) 28 >3.2 was 73.9% and of those with Health Assessment Questionnaire (HAQ) > or =1.5 was 20.9%. There was a statistically significant increase in RF positivity and HAQ scores in the group with higher DAS 28 score. Frequency of extraarticular manifestations was 22.4%. The ratio of the patients receiving disease modifying antirheumatic drugs (DMARD) was 93.1%, and 6.9% of the patients were using anti-tumor necrosis factor (TNF) blocking agents. In AS, the mean age of the patients was 38.1 +/- 10.6, and the female to male ratio was 1:2.5. The time elapsed between the first symptom and diagnosis was 4.3 years. The ratio of peripheral joint involvement was 29.4%. Major histocompatibility complex, class I, B 27 was investigated in 31.1% of patients and the rate of positivity was 91%. In 52.4% of the patients, Bath AS Disease Activity Index (BASDAI) was > or =4. The erythrocyte sedimentation rate, Bath AS Functional Index, and peripheral involvement were significantly higher in the group with BASDAI > or =4. Frequency of extraarticular involvement was 21.2% in AS patients. In the treatment schedule, 77.5% of AS patients were receiving sulphasalazine, 15% methotrexate, and 9.9% anti-TNF agents. Despite widespread use of DMARD, we observed high disease activity in more than half of the RA and AS patients. These results may be due to relatively insufficient usage of anti-TNF agents in our patients and therefore these results mostly reflect the traditional treatments. In conclusion, analysis of disease characteristics will inform us about the disease severity and activity in RA and AS patients and could help in selecting candidate patients for biological treatments. | |
17165004 | Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis. | 2006 | We report a 62-year-old man with rheumatoid arthritis (RA) who developed nodulosis after methotrexate (MTX) treatment. The epithelioid cells of nodules were positive for matrix metalloproteinases (MMP)-2, MMP-3, MMP-9, and Ki67. The synovial tissues obtained from the same patient were negative for MMP-3, MMP-9, and Ki67. This study demonstrated that MTX-induced nodules are different from synovial tissues in terms of MMP expression, suggesting the presence of different pathologic mechanisms and differential MTX susceptibility. | |
18388514 | Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and | 2008 May | PURPOSE OF REVIEW: To outline recent research findings with nonmethotrexate disease-modifying antirheumatic drugs in rheumatoid arthritis and seronegative arthritis spanning systematic reviews, randomized controlled trials, observational clinical practice trials and assessments of adverse effects. RECENT FINDINGS: Systematic reviews show no important differences between methotrexate, leflunomide and sulfasalazine monotherapies; early disease-modifying antirheumatic drug therapy reduces erosive progression. Observational studies show that nonmethotrexate disease-modifying antirheumatic drugs are widely prescribed; their usage has increased in the biologic era. A systemic review also showed patients who failed monotherapy benefited from disease-modifying antirheumatic drug combinations without excess toxicity. Randomized controlled trials of intensive initial disease-modifying antirheumatic drug combinations showed they reduce synovitis and erosive damage, especially when used with steroids. The subsequent sequence of disease-modifying antirheumatic drugs and the value of changing disease-modifying antirheumatic drug monotherapies or stepping-up to combination disease-modifying antirheumatic drugs are, however, unresolved. The adverse risks of nonmethotrexate disease-modifying antirheumatic drugs have been evaluated, including infections and lung disease; patient-related risks seem more important than drug-related risks, though several disease-modifying antirheumatic drugs increase both types of adverse reactions. Two limitations of nonmethotrexate disease-modifying antirheumatic drugs are reduced impact on comorbidities like cardiovascular disease and reduced patient and clinician preferences for these treatments. SUMMARY: Nonmethotrexate disease-modifying antirheumatic drugs are effective, relatively well tolerated and widely used. Their role in intensive treatment strategies in early rheumatoid arthritis appears of crucial importance. |