Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
11950005 Open label study to assess infliximab safety and timing of onset of clinical benefit among 2002 Apr OBJECTIVE: To assess the timing of onset of clinical benefit following the initial infusion of infliximab and to obtain additional safety experience of infliximab when given in an office setting to patients with rheumatoid arthritis (RA). In addition, the safety of reducing the infusion time from 2 hours to 1 hour was evaluated. METHODS: Patients (n = 553) with active RA despite receiving methotrexate (MTX) were treated with infliximab 3 mg/kg given over 2 h at baseline (Week 0), and Weeks 2, 6, and 14 in this multicenter open-label trial. Patients continued to receive a stable dose of MTX (> or = 7.5 mg/wk). At selected sites, patients tolerating the first 4 infusions were eligible to receive 2 additional infusions at twice the usual infusion rate (given over 1 h). Patients returned for efficacy assessments at 48 h following the initial infusion and several times throughout study participation. RESULTS: By 48 h following the first infusion, significant (p < 0.001) improvements were observed in duration of morning stiffness (34% mean improvement), physician's global disease assessment scores (30%), patient's global disease assessment scores (25%), and patient's pain assessment scores (30%). By Week 16, 52 to 63% mean improvements in these efficacy variables were observed (p < 0.001), the significant improvement was maintained through the end of study participation in the subset of patients who received the additional 1 h infliximab infusions. Through 16 weeks, 10% (54/553) of patients reported an adverse event associated with at least 1 of the 4 infusion procedures; the majority were mild and transient in nature. In the subset of 197 patients who received 2 additional infusions over 1 h, no increase in the frequency or severity of infusion-related adverse events was observed compared to the 2 h infusion. CONCLUSION: Infliximab administered to patients with RA in an outpatient setting resulted in significant clinical improvement within 48 h that was sustained with additional infusions. Approximately 10% of patients experienced an infusion reaction, highlighting the need for direct supervision over patient treatment. Patients who tolerated infliximab infusions given over 2 h also tolerated a 1 h infusion.
12003373 Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. 2002 Apr Leflunomide, a new oral immunomodulatory agent, is effective for the treatment of rheumatoid arthritis. Its mechanism of action in suppressing inflammation is based in its inhibition of dihydroorotate dehydrogenase, an enzyme responsible for de novo synthesis of pyrimidine containing ribonucleotides. It is the first disease-modifying antirheumatic drug approved for treatment of rheumatoid arthritis with an indication for retardation of joint damage by radiography. Side effects are generally mild and include diarrhea, rashes, reversible alopecia, and elevation of hepatic transaminases. Despite the concern about hepatotoxicity, combination use with methotrexate in treating patients with rheumatoid arthritis has been shown to be safe. Other autoimmune diseases in which leflunomide has been used successfully include Felty syndrome, vasculitis, Sjogren syndrome, Wegener granulomatosis, and bullous pemphigoid.
15053456 Ten-year radiographic outcome in patients with rheumatoid factor positive rheumatoid arthr 2004 Mar We observed 10-year radiographic outcomes in patients with rheumatoid factor positive rheumatoid arthritis prospectively. Group I, II, and III comprised 87, 125, and 89 consecutive subjects with disease duration at presentation of less than 4, 4-24, and 25-255 months, respectively. Initial therapy was with combinations of pulse intravenous (i.v.) methylprednisolone (0-125 mg), cyclophosphamide (100-200 mg), methotrexate (MTX, 5-15 i.v. mg/week) and simultaneous oral cyclosporin A (CSA, 25 mg bid/tid). After disease was controlled i.v. therapy was tapered and switched to oral MTX + CSA. Outcomes from the Larsen Index and Erosive Joint Count were compared in cases and in dropouts with baseline and each other. Significant improvement in the Larsen Index and Erosive Joint Count was observed in Group I (p < 0.0001). In Group II and III the improvement or deterioration was not significant. The Larsen Index and Erosive Joint Count deteriorated significantly in the dropouts compared with baseline and cases (p < 0.0001). In conclusion, in early RA, in a Malayo-Polynesian patient sample, radiological progression could be halted with aggressive combination treatment.
12892252 Serum levels of cartilage oligomeric matrix protein. A predicting factor and a valuable pa 2003 OBJECTIVE: To examine whether cartilage oligomeric matrix protein (COMP) correlates with inflammation and/or joint destruction of patients with rheumatoid arthritis (RA) and to test COMP as predicting factor for the outcome of patients with established RA. METHODS: Serum levels of COMP were measured in sera of 62 patients, suffering from RA according to the ACR criteria and treated in intervals in our department, over a period of 5 years. A commercially available sandwich--type ELISA-kit developed by AnaMar Medical AB, Sweden, was used. The results of serum COMP were compared with the Disease Activity Score (DAS), the Larsen Score, and clinical and laboratory parameters. RESULTS: We found a positive correlation between serum levels of COMP at baseline and deterioration of Larsen score even after 5 years (p < 0.007; r = 0.34). To confirm serum COMP as an independent predicting factor for patients with RA we looked at a subgroup of patients (n = 17) with elevated serum levels of COMP (mean 11,7 U/l) and low clinical prognostic factors. In this subgroup we also found a significant correlation with delta Larsen score (p < 0.01; r = 0.59) after 5 years. CONCLUSION: Serum levels of COMP is known to reflect increased cartilage turnover. The results indicate that serum COMP may be used as a prognostic marker of cartilage degradation in a patient group with established RA.
15077288 Slowing of bone loss in patients with rheumatoid arthritis by long-term high-intensity exe 2004 Apr OBJECTIVE: Patients with rheumatoid arthritis (RA) are more at risk for the development of osteoporosis and osteoporotic fractures than are their healthy peers. In this randomized, controlled, multicenter trial, the effectiveness of a 2-year high-intensity weight-bearing exercise program (the Rheumatoid-Arthritis-Patients-In-Training [RAPIT] program) on bone mineral density (BMD) was compared with usual care physical therapy, and the exercise modalities associated with changes in BMD were determined. METHODS: Three hundred nine patients with RA were assigned to an intervention group, either the RAPIT program or usual care physical therapy. The primary end points were BMD of the hip and spine. The exercise modalities examined were aerobic fitness, muscle strength, and, as a surrogate for those effects not directly measured by the RAPIT program, attendance rate. RESULTS: The data on the 136 RAPIT participants and 145 usual care participants who completed the study were analyzed. The mean rate of decrease in hip BMD, but not in lumbar spine BMD, was smaller in patients participating in the RAPIT program when compared with that in the usual care group, with a mean decrease of 1.6% (95% confidence interval [95% CI] 0.8-2.5) over the first year and 0.5% (95% CI 1.1-2.0) over the second year. The change in hip BMD was significantly and independently associated with changes in both muscle strength (multivariate odds ratio [OR] 1.75, 95% CI 1.07-2.86) and aerobic fitness (OR 1.79, 95% CI 1.10-2.90), but not with the attendance rate (OR 1.00, 95% CI 0.99-1.00). CONCLUSION: A long-term high-intensity weight-bearing exercise program for RA patients is effective in slowing down the loss of BMD at the hip. The exercise modalities associated with this effect are muscle strength and aerobic fitness.
12390945 Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with 2002 Oct 22 BACKGROUND: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-alpha in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-alpha antibody infliximab on disease activity and endothelial function in patients with active RA. METHODS AND RESULTS: Eleven RA patients (mean age 46+/-5 years; disease duration 9+/-2 years) with high disease activity despite treatment with stable doses of methotrexate (
15455955 [Case of rheumatoid arthritis presenting with pulmonary tuberculosis]. 2004 Aug A 72-year-old man who had been suffering from rheumatoid arthritis for 25 years developed pulmonary tuberculosis after treatment with infliximab. He had been receiving this treatment since December 2003. Forty-six days later, a fever developed and the patient was hospitalized on February 3, 2004. Chest radiography and chest CT showed an infiltrative shadow with cavity formation. Mycobacterium tuberculosis was detected in the sputum. Infliximab is a monoclonal antibody toward tumor necrosis factor alpha (TNFalpha). It has been reported that infliximab increases the risk of tuberculosis in patients with rheumatoid arthritis in Europe and North America. This is the first case of pulmonary tuberculosis in a patient treated with infliximab in Japan.
12658861 Age at diagnosis of smoking-related disease. 2003 Feb OBJECTIVES: This study assesses the relationship between the age of daily smoking initiation and the age at diagnosis of chronic obstructive pulmonary disease (COPD), heart disease and rheumatoid arthritis. DATA SOURCE: The data are from the 2000/01 Canadian Community Health Survey (CCHS). The sample for the analysis consisted of 34,144 respondents aged 35 to 64 living in private households in the provinces and territories. ANALYTICAL TECHNIQUES: The life table approach was used to estimate the cumulative incidence of smoking-related disease. Cox proportional hazards regression models were used to estimate the relative risks of disease by the age when daily smoking began. MAIN RESULTS: For both sexes, the younger the individuals were when they became daily smokers, the sooner they were diagnosed with COPD, heart disease or rheumatoid arthritis. Even when education, household income and number of cigarettes smoked per day were taken into account, adolescent starters were at increased risk of these diseases, compared with never-smokers.
15103251 Functional genomics of fibroblasts. 2004 May PURPOSE OF REVIEW: Successful analysis of the pathophysiology of rheumatoid arthritis requires the functional understanding of interactions between different cell types and the cell matrix, intracellular signaling pathways, as well as between cartilage, bone, and synovium in rheumatoid arthritis. During the review period, molecular biology has provided and used a growing number of tools to screen the genome such as gene and protein chips, haplotype analysis, and single nucleotide polymorphism analysis, resulting in various novel findings with considerable impact on the overall understanding of rheumatoid arthritis. RECENT FINDINGS: Key issues that have been addressed and elucidated by numerous research groups are the regulation and modulation of synovial fibroblast metabolism and activation by proinflammatory cytokines and chemokines. In addition, examination of adhesion processes and neoangiogenesis has revealed new insights into the interaction network between rheumatoid synovial fibroblasts and the surrounding matrix and cells. Finally, a more detailed view of activation of these fibroblasts has been obtained by analysis of the molecular balance between cellular activation and regulation of apoptosis. SUMMARY: Although high throughput molecular analysis methods provided an ample amount of novel data, it needs to be stressed that a one-method approach of gene expression (eg, by array analysis) is not sufficient to validate the gene/gene product as a new therapeutic target. Therefore, the next steps are the so-called functional genomics or functionomics, which intend to reveal relations between the obtained data and to unveil their interactions for a better understanding of the pathogenesis and the mechanisms that are operative in rheumatoid arthritis.
15249317 Sustained maintenance of exercise induced muscle strength gains and normal bone mineral de 2004 Aug OBJECTIVE: To investigate at 5 years whether an initial 2 year home based strength training period imposes sustained effects on muscle strength, bone mineral density (BMD), structural joint damage, and on disease activity in patients with early rheumatoid arthritis (RA). METHODS: Seventy patients were randomised either to perform home based strength training with loads of 50-70% of repetition maximum (EG) or range of motion exercises (CG). Both groups were encouraged to take part in aerobic activities 2-3 times a week. Maximal muscle strength of different muscle groups was measured by dynamometers, and BMD at the femoral neck and lumbar spine by dual x ray densitometry. Disease activity was assessed by the 28 joint disease activity score, and joint damage by x ray findings. RESULTS: 62 patients completed 2 years' training and 59 patients attended check up at 5 years. Mean (SD) maximum muscle strength indices increased from baseline to 2 years-in EG from 212 (78) kg by a mean (95% CI) of 68 (55 to 80) and in CG from 195 (72) kg by 35 (13 to 60) kg-and remained at that level for the next 3 years. Development of BMD in EG tended to be more favourable than that in CG. Muscle strength training was not detrimental to joint structures or disease activity. CONCLUSION: The patients' exercise induced muscle strength gains during a 2 year training period were maintained throughout a subsequent self monitored training period of 3 years. Despite substantial training effects in muscle strength, BMD values remained relatively constant. Radiographic damage remained low even at 5 years.
15624449 The broadening use of leflunomide in clinical practice. 2004 Dec Autoimmune diseases make up a large proportion of chronic disease care. Inducing remission by immunosuppression remains the cornerstone of long-term management. This article reviews the place of leflunomide in clinical practice and outlines its potential applications beyond its licenced indication, rheumatoid arthritis.
11929337 Newer immunosuppressive drugs: their potential role in rheumatoid arthritis therapy. 2002 Rheumatoid arthritis (RA) is a chronic immune-mediated disease characterised by chronic synovitis, which leads to cartilage damage and joint destruction. It is generally a progressive disease with radiographic evidence of joint damage, functional status decline and premature mortality. Proinflammatory cytokines, such as interleukin 1 and tumour necrosis factor alpha, play an important role in maintaining the chronicity of RA and mediating tissue damage. New approaches in the therapy of RA with anticytokine biological agents, which neutralise or block cytokines or their receptors, are now the first generation antirheumatic drugs in clinical practice. A better understanding of the signal transduction systems and gene regulation by transcription factors involved in cytokine production has opened the way for the discovery of novel therapeutic compounds useful in treating patients with RA. Overactivation of selective kinases or aberrant function of downstream transcription factors could help convert a normal immune response to a chronic disease state. This provides a unique opportunity for novel therapeutic interventions, since specific signal transduction or transcription factor targets might interrupt the perpetuation mechanisms in RA. The availability of potent and selective p38 mitogen activated protein kinase inhibitors provide a means in further dissecting the pathways implicated in cytokine production, which in turn maintain the chronicity of RA. Many studies conclude that these compounds are very useful in the treatment of chronic synovitis and therefore are very promising for RA treatment.
11973000 The relationship of pain and depression to cognitive function in rheumatoid arthritis pati 2002 Apr The purpose of this study was to assess the hypothesis that pain and depression negatively impact the cognitive functioning of individuals with rheumatoid arthritis (RA). One hundred twenty-one community-dwelling RA patients (ages 34-84) completed a battery of cognitive tasks and multiple measures of pain and depression. Structural equation modeling techniques were used to assess the relative contributions of pain, depression, and age to cognitive performance. Individuals who performed poorly on cognitive tasks reported more pain and depression and were older than those individuals who performed well on cognitive tasks. Moreover, high levels of pain were associated with depression. Further analyses revealed that depression mediated the relationship between pain and cognition. That is, when depression was entered into the analyses, the previously significant effects of pain on cognition were no longer found. Interestingly, depression still mediated the pain-cognition relationship even after controlling for age. These findings suggest the importance of both pain and depression for understanding cognitive function in RA and may have important implications for treating this disease.
14740449 Active MMPs captured by alpha 2 macroglobulin as a marker of disease activity in rheumatoi 2003 Nov OBJECTIVE: The aim of the present study was to analyze alpha 2 Macroglobulin/MMP (alpha 2M/MMP) complex formation and to investigate whether MMP activity in alpha 2M/MMP complexes in serum can be used as a disease marker in rheumatoid arthritis (RA). METHODS: High and low molecular weight (H/LMW) substrates and inhibitors and size exclusion were used to analyze alpha 2M/MMP complex formation. LMW fluorogenic substrates were used to quantify the level of MMPs in alpha 2M/MMP complexes in the serum of RA patients and healthy controls. RESULTS: Active MMPs were fully inhibited by LMW inhibitor BB94 in the presence of alpha 2M, whereas no inhibition was achieved by HMW inhibitor TIMP-1. Size exclusion analysis showed alpha 2M/MMP complex formation in buffer and in normal plasma spiked with activated MMPs, which indicated alpha 2M/MMP complex formation in the systemic circulation. MMP activity in alpha 2M/MMP complexes in the serum of RA patients was significantly higher than in the serum of healthy controls (P < 0.001). MMP activity levels in the serum of RA patients were correlated with ESR (r = 0.72, P < 0.001). CONCLUSION: In the systemic circulation of RA patients, active MMPs form complexes with alpha 2M and can be detected using LMW fluorogenic substrates. MMP activity measurements in serum allow discrimination between RA patients and healthy controls and provide a new tool for the assessment of the disease process in RA.
15098366 [Endoprosthetic procedures in rheumatoid patients]. 2003 Rheumatoid diseases are generalized chronic inflammatory diseases of the musculoskeletal system. Although the different structures and different joints are affected, all cause a very uniform type of pathology and joint destruction. The main indication for implantation of the endoprosthesis are severe pain and walking disability with poor quality of life. On the X-ray involvement includes periarticular osteopenia, cystic changes, and destruction's affected joints. Endoprosthetic replacement has been successful in the treatment of severe rheumatoid disease of almost all joints of all ages, but predominantly replacement of the hip, knee, shoulder, elbow and MCP joints. Arthroplasty has proved to be an excellent addition to the therapeutic armamentarium for the rehabilitation of handicapped patients with rheumatoid disease. Advancements in endoprosthetic technology and surgical techniques, allow us to perform alloarthroplasty in most of the patients with severe rheumatoid disease of all different joints.
15008310 Autoimmune diseases in a Nigerian woman--a case report. 2003 Dec Autoimmune diseases (AD) are conditions in which there is the development of antibodies against self cells/ organs. AD could either be organ-specific or non-organ specific (systemic) in clinical presentation. Commonly reported ADs includes: Myasthenia gravis, Hashimoto thyroiditis, Guillian-Barre syndrome, vitiligo, type 1 diabetes mellitus, Graves diseases, Goodpastures syndrome, pemphigus, rheumatoid arthritis, systemic lupus erythematosis, Addisons disease, multiple sclerosis, pernicious anaemia, autoimmune haemolytic anaemia, chronic active hepatitis, idiopathic thrombocytopenic purpura. There is paucity of locally documented information on the occurrence of AD in same patient in our environment. We therefore report the case of a 66 year old woman who presented at the University College Hospital (UCH), Ibadan, with a spectrum of the AD, Vitiligo, rheumatoid arthritis, myasthenia gravis, impaired glucose tolerance.
15537054 Gene therapy for autoimmune diseases. 2004 Oct Autoimmune diseases are threatening an increasing number of patients in developed countries, representing one of the major causes of disability and an enormous social cost. Current therapies mainly treat the symptoms of autoimmune diseases and are only partially able to interfere with disease evolution, and therefore decrease the degree of physical impairment. Thus, the development of new therapeutic strategies is imperative. This review focuses on gene therapy, as one possible alternative approach to the treatment of autoimmune disorders. The potential of gene therapy to specifically target tissues affected by autoimmune aggression, and its ability to interfere with the destructive pathogenic process while providing functional replacement and fostering reparative mechanisms will be emphasized. Gene therapy studies in experimental models of diabetes, rheumatoid arthritis and multiple sclerosis are reviewed.
20217663 The immune system and new therapies for inflammatory joint disease. 2003 Mar This article provides an overview of the immune system with a specific focus on the role of biologic therapies in treating the consequences of an altered immune response as seen in rheumatoid arthritis (RA). Cytokines are powerful chemical messengers that have a significant role to play in activating an inflammatory response. Two dominant cytokines have been identified as crucial in the inflammatory process that can be seen in RA-tumour necrosis factor alpha (TNFalpha) and interleukin-1. The term 'biologic' is used to describe biologically engineered therapies that are specifically designed to prevent pro-inflammatory cytokines inducing an inflammatory response. Research trials and now clinical practice have clearly demonstrated a significant benefit to patients receiving biologic therapies. The responsibility of the practitioner is to ensure a sound knowledge of biologic therapies, to understand the essential aspects of care and to recognize the importance of guidance documents available to support management and, ultimately, the long-term provision of safe and effective administration of these therapies.
12858440 Diagnostic value of anti-cyclic citrullinated Peptide antibody in patients with rheumatoid 2003 Jul OBJECTIVE: To explore the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) detected by ELISA in patients with rheumatoid arthritis (RA). METHODS: The synthesized cyclic citrullinated peptide was used as substrate for ELISA. Anti-CCP antibody was detected by ELISA in 191 patients with RA, 132 with rheumatic diseases other than RA, and 98 with nonrheumatic diseases. The antiperinuclear factor (APF), anti-keratin antibody (AKA), rheumatoid factor (RF), and HLA-DR4 gene complex were also tested in each RA patient. The results of these tests were compared with anti-CCP antibody to examine the correlation between them. RESULTS: Ninety (47.1%) patients with RA, 4 (3.0%) with other rheumatic diseases, and 2 (2.0%) with nonrheumatic diseases were found to be anti-CCP antibody positive by ELISA. The sensitivity of anti-CCP antibody was 47.1%, with a high specificity (97.4%) in RA. Anti-CCP antibody correlated with APF, AKA, RF, and HLA-DR4 gene complex. CONCLUSION: A new modified anti-CCP antibody test had a moderate sensitivity (47.1%) but a high specificity (97.4%) in patients with RA and was found as a valuable supplement to diagnosis of RA. Anti-CCP correlated with APF, AKA, RF, and HLA-DR4 gene complex, but did not completely overlap with them. Anti-CCP antibody could be regarded as a new diagnostic marker for RA.
15552523 Overview of benefit/risk of biological agents. 2004 Sep Targeted tumor necrosis factor-alpha antagonists, first approved by the FDA in 1998, have had a significant impact on the treatment of patients with rheumatoid arthritis. In general, the benefit/ risk ratio for these agents and the IL-1 receptor antagonist, anakinra, has been quite favorable. However, infrequent adverse events can be serious and require continued pharmacovigilance. Infections, particularly tuberculosis and less commonly fungal infections, are among the most serious adverse events, especially given delays in diagnosis due to subtle or atypical presentations. Questions have also arisen regarding whether anti-TNF-alpha agents increase the risk of lymphoma, a complicated issue confounded by the multiple risk factors for lymphoma in patients with rheumatoid arthritis and low observed incidence rates of lymphoma, requiring prolonged monitoring. Additional rare reported complications include systemic lupus erythematosus-like syndromes, congestive heart failure and demyelinating syndromes (including cases resembling progressive multifocal leukoencephalopathy). Ongoing post-marketing surveillance of these and other serious adverse events is necessary to determine the true incidence rates, and whether a reassessment of the overall risk-benefit of tumor necrosis factor-alpha antagonists will be required.