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ID PMID Title PublicationDate abstract
18157679 Patient access to rheumatoid arthritis treatments. 2008 Jan This paper is an introduction to the study "The Burden of Rheumatoid Arthritis and Patient Access to Treatment". The objective of the study is to compare patient access to new drugs in Europe, North America and a selection of other countries, and to analyse the determinants of differences between countries, as basis for a discussion on how patients' access to new and effective treatments can be improved. There were few treatments available that could affect the progression of the disease prior to the introduction of the first TNF inhibitors in the late 1990s. Since the cost per patient treated with these biological drugs is high compared to previously available treatments, reimbursement through private and public insurance is an important determinant for access to treatment.
17912575 The interrelation of glutathione reductase, catalase, glutathione peroxidase, superoxide d 2008 Feb Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis, a systemic autoimmune disease characterized by chronic inflammation of the synovial joints, ultimately leading to joint destruction and permanent disability, affecting 1% of the world population. Oxidative stress in rheumatoid inflammation, due to the fact that antioxidant systems are impaired in RA and caused by fee radicals, might have an essential role in etiology of RA. This review includes the interrelation of antioxidants against free radicals in RA patients. There is much evidence that antioxidant team that covers glutathione reductase, catalase, glutathione peroxidase, superoxide dismutase, and glucose-6-phopshate destroy reactive oxygen species and other free radicals through enzymatic as well as nonenzymatic means. The change in relative levels of antioxidants vis-à-vis free radical formation and level could be used as indicators for effective and earlier diagnosis of RA.
16010277 Transoral anterior approach for extensive anterior decompression at the C3 vertebra level 2006 Jan STUDY DESIGN: We report a successful extensive transoral anterior decompression for an elderly patient with myelopathy and occipitalgia due to severe atlantoaxial vertical subluxation and posterior subluxation of the axis associated with rheumatoid arthritis (RA). OBJECTIVE: To describe the treatment of an exceptional pathological condition involving severe vertical subluxation. SETTING: University-affiliated hospital in Gifu, Japan. METHODS: A 73-year-old woman was referred to our clinic because of myelopathy and occipitalgia due to severe atlantoaxial vertical subluxation and posterior subluxation of the axis associated with RA. Plain radiographs revealed severe atlantoaxial vertical subluxation and sagittal magnetic resonance (MR) imaging revealed severe compression of the spinal cord at the level of the C2/3 disc space due to both posterior subluxation of C2 and rheumatoid pannus at the C2/3 disc space. As MR images demonstrated that the C2/3 disc space was located just behind the retropharyngeal wall, we performed successful anterior decompression from C2 to C3 via the standard transoral approach without mandibular osteotomy. RESULTS: The patient has been followed for 4 years and her symptoms are currently much improved without further surgical treatment. CONCLUSIONS: The present case illustrates that severe atlantoaxial vertical subluxation and posterior subluxation of the axis associated with RA can be treated successfully by anterior decompression of C2 and C3 via the standard transoral approach.
17985406 Significant association of insertion/deletion polymorphism of the angiotensin-converting e 2007 Dec OBJECTIVE: Only 30% of the genetic contribution to rheumatoid arthritis (RA) can be attributed to HLA genes, and other non-HLA genes may play a role in RA susceptibility. Angiotensin-converting enzyme (ACE) has been reported to be involved in pathogenesis of RA, and high levels of ACE have been documented in RA synovial fluid and pleural effusions. Since plasma and tissue levels of ACE are determined at the transcriptional level, we test the hypothesis that the genotype of ACE in RA patients may be a determining factor in pathogenesis. METHODS: Sixty patients with RA were recruited and clinically characterized according to disease duration, disease severity, disease activity, and American College of Rheumatology functional classes. ACE gene I/D polymorphism genotypes were determined in patients and healthy controls, using polymerase chain reaction. RESULTS: We found a significant overrepresentation of the DD genotype and the D allele in patients with RA; and we found that men with RA exhibited a higher frequency of the DD genotype and D allele compared to male controls. By logistic regression analysis the DD genotype confers a relative risk for development of RA of 3. CONCLUSION: Our study found an association between ACE deletion polymorphism and RA.
18077493 Long-term exposure to medium-dose glucocorticoid therapy associates with hypertension in p 2008 Jan OBJECTIVE: Rheumatoid arthritis (RA) associates with increased cardiovascular morbidity and mortality that is due to both traditional and novel cardiovascular risk factors. Hypertension (HT), one of the most common risk factors for cardiovascular disease, is highly prevalent in RA. The effects of long-term glucocorticoid (GC) therapy on blood pressure have not been established yet. This study examined whether GC exposure associates with HT in patients with RA. METHODS: Four hundred consecutive RA patients with detailed clinical and laboratory assessments were categorized into three groups according to GC exposure: no or limited exposure (N/L-E); a low-dose (< 7.5 mg) long-term exposure (LD/LT-E); and medium-dose (> or = 7.5 mg) long-term exposure (MD/LT-E). The association of GC exposure with HT was evaluated using logistic regression analysis. RESULTS: HT was more prevalent in the MD/LT-E group (84.7%) than the LD/LT-E or N/L-E groups (70.7 and 67.3%, respectively, P = 0.028). Logistic regression revealed increased odds for HT when comparing MD/LT-E with N/L-E, after adjustment for HT risk factors [odds ratio (OR) = 2.57, 95% CI 1.01-6.56, P = 0.049] and RA disease characteristics (OR = 3.64, 95% CI: 1.36-9.77, P = 0.01). CONCLUSIONS: MD/LT GC exposure associates with a very high prevalence of HT. This appears to be independent of other risk factors for HT or of channelling bias due to disease severity, even though the latter cannot be excluded given the cross-sectional nature of our study. RA patients in this GC exposure group should be particularly targeted for early identification and aggressive management of HT.
18438830 Denosumab treatment effects on structural damage, bone mineral density, and bone turnover 2008 May OBJECTIVE: RANKL is essential for osteoclast development, activation, and survival. Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL, inhibiting its activity. The aim of this multicenter, randomized, double-blind, placebo-controlled, phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis (RA) receiving methotrexate treatment. METHODS: RA patients received subcutaneous placebo (n = 75), denosumab 60 mg (n = 71), or denosumab 180 mg (n = 72) injections every 6 months for 12 months. The primary end point was the change from baseline in the magnetic resonance imaging (MRI) erosion score at 6 months. RESULTS: At 6 months, the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group (mean change 0.13; P = 0.118) and significantly lower in the 180-mg denosumab group (mean change 0.06; P = 0.007) than in the placebo group (mean change 1.75). A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group (P = 0.019) as compared with placebo, and at 12 months, both the 60-mg (P = 0.012) and the 180-mg (P = 0.007) denosumab groups were significantly different from the placebo group. Denosumab caused sustained suppression of markers of bone turnover. There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity. Rates of adverse events were comparable between the denosumab and placebo groups. CONCLUSION: Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited structural damage in patients with RA for up to 12 months, with no increase in the rates of adverse events as compared with placebo.
17279112 [Specialized rehabilitation of patients with rheumatic disease]. 2007 Feb 1 Patients with serious rheumatic disease do not only need treatment for the medical consequences of their disease, but also for the psychological, social and economic consequences. This article gives an overview of specialized rehabilitation within rheumatology in Norway and presents the National Resource Centre for Rehabilitation in Rheumatology (NRRK). NRRK offers treatment to patients with complicated inflammatory rheumatic disease. Rehabilitation at NRRK is multidisciplinary, client-centred, goal-directed and coping-oriented, and offers rehabilitation when no satisfactory service is available on a local or regional level. Documentation of treatment effects after rehabilitation at NRRK is briefly presented. Several self-reported health status variables (fatigue, coping, physical function, and several quality of life dimensions in SF-36) improved during the rehabilitation stay and up to 6 months follow-up. Cost aspects are of great importance for rehabilitation services in rheumatology, but have only been evaluated to a minor degree. Documenting effects of rehabilitation interventions remains an important challenge; evaluation should include the whole rehabilitation concept.
16765714 Rheumatoid pleural effusion. 2006 Jun OBJECTIVES: To describe the clinical and laboratory features of rheumatoid pleural effusion (RPE) and the diagnostic and therapeutic approaches to this condition. METHODS: The review is based on a MEDLINE (PubMed) search of the English literature from 1964 to 2005, using the keywords "rheumatoid arthritis" (RA), "pulmonary complication", "pleural effusion", and "empyema". RESULTS: Pleural effusion is common in middle-aged men with RA and positive rheumatoid factor (RF). It has features of an exudate and a high RF titer. Underlying lung pathology is common. Generally RPE is small and resolves spontaneously but symptomatic RPE may require thoracocentesis. Rarely, RPE has features of a sterile empyematous exudate with high lipids and lactate dehydrogenase, and very low glucose and pH levels. This type of effusion eventually leads to fibrothorax and lung restriction. Superimposed infective empyema often complicates RPE. Oral, parenteral, and intrapleural corticosteroids, pleurodesis and decortication, have been used for the treatment of sterile RPE. Infected empyema is treated with drainage and antibiotics. CONCLUSIONS: RPE may evolve into a sterile empyematous exudate with the development of fibrothorax. Symptomatic effusions or suspicion of other causes of exudate (infection, malignancy) require thoracocentesis. The "rheumatoid" nature of the pleural exudate in patients without arthritis mandates a pleural biopsy to exclude tuberculosis or malignancy. The optimal therapy of RPE has yet to be established. The role of cytokines in the course of RPE and the possible usefulness of cytokine blockade in the treatment of this RA complication require further evaluation.
17708740 Interleukin-6 inhibition and clinical efficacy in rheumatoid arthritis treatment--data fro 2007 Interleukin 6 (IL-6), a pleiotropic cytokine with numerous and varied effects on the inflammatory cascade and immune response, appears to be an attractive target for novel immunomodulatory therapy for systemic inflammatory autoimmune diseases. Proof of principal for this approach has come from studies of the anti-IL-6 receptor monoclonal antibody, tocilizumab. Tocilizumab has been assessed in a number of studies in recent years, mainly in patients with rheumatoid arthritis (RA). Data from randomized controlled clinical trials demonstrate the efficacy of tocilizumab in improving the signs and symptoms of RA. In addition, it appears that such inhibition of IL-6 can have positive effects on functional status, an important outcome for RA patients. Finally, data suggest that treatment with this agent may also inhibit the progression of disease as assessed radiographically. Data from studies currently underway will help refine the ultimate use of this novel approach to treatment, and help clinicians optimize therapy using this approach.
17336603 Serum protein profile of rheumatoid arthritis treated with anti-TNF therapy (infliximab). 2007 Aug We analyzed the changes in the serum protein profile by infliximab using two-dimensional gel electrophoresis and mass spectrometry. More than 50 gel spots were seen to increase or decrease in correlation with clinical improvements of RA. The spots corresponding to CRP, C3, and Apo J showed reduced staining intensity, while the spots corresponding to Apo A-I, RBP, and transthyretin were enhanced. The protein profile of RA patients treated with infliximab was mostly similar to that of normal healthy controls except for several protein spots. This suggested that infliximab normalized the serum protein profile of RA patients, leading to modification in the serum lipid profile and antioxidant status in RA.
18759706 Risk of skin cancer in the drug treatment of rheumatoid arthritis. 2008 Sep BACKGROUND: It is well established that rheumatoid arthritis (RA) is associated with an increased risk of lymphoproliferative disorders when compared to the general population. It remains unclear whether this risk is owing to underlying inflammation and immune dysregulation, effects of disease modifying medications or a combination of the two. With increasing use of targeted biologic therapies, including those that may theoretically interfere with innate tumor surveillance, there is increasing concern about the development of other malignancies. METHODS: The English language literature was searched to identify observational studies and clinical trials reporting incidence and relative risk of melanoma and non-melanoma skin cancer (NMSC) among RA patients. RESULTS/CONCLUSIONS: The numbers of melanomas reported were too small to draw conclusions regarding increased or decreased risk with underlying RA or commonly used medications. Relative incidence of NMSCs is difficult to assess given the lack of standardized reporting in the general population. No safety signal concerning skin cancer with RA or its therapies is at present identified.
17678723 Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort. 2007 Aug Recently, a genome-wide association study identified the interleukin-23 receptor gene (IL23R) as an inflammatory bowel disease (IBD) associated gene. Given the involvement of IL23R in T-cell regulation, we decided to test whether this gene is associated with rheumatoid arthritis (RA). Eight IL23R gene polymorphisms (rs1,004,819, rs7,517,847, rs10,489,629, rs11,209,026, rs1,343,151, rs10,889,677, rs11,209,032, and rs1,495,965) were selected among the 10 most associated SNPs from the IBD study. A total of 322 RA patients and 342 healthy controls were genotyped for the selected SNPs using a Taqman 5' allelic discrimination assay. We did not find statistically significant differences when we compared allele and genotype frequencies between RA patients and controls for none of the IL23R gene polymorphisms under study. We did not observe significant differences when RA patients were stratified according to their clinical and demographic features. We conclude that the IL23R gene does not seem to be associated with RA predisposition in a Spanish population.
18421172 Clinical and histopathological evaluation of MDP/collagen induced arthritis rat model (MCI 2008 Apr This study was done to assess the effects of Urtica dioica, Plantago major and Hypericum perforatum L herbal mixture in the MCIA rat model. In addition, a new pathological and clinical arthritis lesion assessment was developed. Sprague-Dawley (SD) rats were immunized with bovine type II collagen and muramyl dipeptide (MDP). Commercial herbal extracts were administered daily to the rats after the immunization for the course of experiment (90 days). Rats were boosted with a second collagen-MDP emulsion 60 days after the first immunization. Paws were daily evaluated macroscopically for redness, swelling, distortion, or ankylosis of the joints. On the day of sacrifice, rat paws were assessed for histopathologic changes. Herbal mixture administration decreased the clinical lesion manifestation in the MCIA rat model and led to development of similar or slightly more severe histopathological lesions compared to rats that did not receive the treatment. The clinical arthritis signs appeared as early as 13 days after the first MDP/collagen injection and with peak incidence at 20 days post-immunization. Histopathologically, animals showed changes ranging from mild to very severe. Administration of the herbal mixture used in this study had a clinical therapeutic effect on the course of the clinical manifestations in the MCIA model, but the herbal treatment had no such effect on the histopathological lesion development and even led to slightly more severe lesions. Rats in the MCIA model developed prominent clinical and histopathological changes that were comparable to rheumatoid arthritis (RA) lesions in humans.
17641872 [Differences in elbow replacement in rheumatoid arthritis]. 2007 Aug Between 1987 and 2005, 165 patients with rheumatoid arthritis of the elbow, four with psoriatic arthritis, and eight with osteoarthrosis of the elbow were treated with total elbow arthroplasty using 126 semiconstrained GSB III elbow replacement prostheses; 46 semiconstrained Coonrad-Morrey prostheses; 24 Souter-Strathclyde unconstrained, unlinked prosthesis; four constrained link hinge prostheses; two custom-made prostheses; and one Pritchard elbow replacement. All implant procedures relieved pain and improved functionality. The complication rate was 34.4%. Revision surgery was needed in 27.2% of elbows because of infection, dislocation, or aseptic loosening. Survival of the semiconstrained implants with ventral or epicondylar flanges for load transfer was better than that of the other implants. Component linkage with the Coonrad-Morrey implant prevents dislocation without increasing the risk of loosening; therefore, semiconstrained implants are our choice for advanced arthritis of the elbow. Total elbow replacement is associated with a high complication rate and therefore may be warranted only for seriously disabled patients.
16159946 Fas (CD95)-related apoptosis and rheumatoid arthritis. 2006 Jan Abnormal proliferation and/or persistence of synoviocytes and inflammatory cells has long been described in inflammatory arthritis conditions, but only relatively recently has substantial attention been drawn to the relevance of abnormal apoptotic processes in disease pathogenesis and treatment. This review summarizes a current understanding of the Fas (CD95)-Fas ligand (CD178) apoptotic system, which has most predominantly been examined in rheumatoid arthritis. There, synovial inflammation is often characterized by a unique resistance to Fas-related apoptosis, and agonistic therapeutic interventions upon Fas have consistently been found beneficial in both animal and human disease models. Therefore, modulation of the Fas pathway will hopefully be of both pathogenic and therapeutic interest in the study of inflammatory arthritis conditions in general.
17611974 What is the place of recently approved T cell-targeted and B cell-targeted therapies in th 2007 Jul The recently approved therapies abatacept and rituximab have significantly improved treatment options for patients with rheumatoid arthritis, especially for patients who have an inadequate response to tumor necrosis factor inhibitors. This article reviews the latest efficacy and safety data for both abatacept and rituximab. One-year data from abatacept and rituximab clinical trials show significantly better efficacy and reduction in radiographic damage for these therapies compared with placebo. In addition, repeated courses of rituximab confer continued efficacy for patients. The safety profile of these therapies shows that infusion reactions and infections are the most commonly reported important adverse events. Premedication with corticosteroids reduces the infusion reactions to rituximab.
17606412 Radiological features of lumbar spinal lesions in patients with rheumatoid arthritis with 2008 Jul BACKGROUND CONTEXT: Compared with the cervical spine, little attention has been paid to rheumatoid arthritis (RA)-related lumbar disorders. Only a few articles have described the status of the lumbar spine affected by RA based on plain X-ray films and magnetic resonance imaging (MRI). PURPOSE: To describe the features and prevalence of radiological changes of the lumbar spine of patients with RA and to clarify the correlations of such features with disease activity. STUDY DESIGN: Transverse radiological study. PATIENT SAMPLE: We radiographically examined 104 patients with RA whose age ranged from 21 to 78 years (mean, 51.0). In each, the duration of RA exceeded 10 years (mean, 17.7 years). OUTCOME MEASURES: Clinical outcomes included Ochi's classification, Lansbury index, C-reactive protein (CRP) (mg/dL), rheumatoid factor (RF) (U/mL), and platelet (count/mm). Radiological outcomes included radiography and MRI. METHODS: One hundred four RA patients were included in this study regardless of the presence/absence of low back pain. We examined discs from L1-2 to L5-S, including endplates, in each patient on plain X-ray films and magnetic resonance images and used a comprehensive grading system to evaluate each feature of the lumbar spine affected by RA based on the present findings and published reports. The correlations of these radiological features with RA activity and Ochi's classification were examined. To quantify disease activity, we determined the Lansbury index, serum CRP (mg/dL), RF (U/mL), and platelet count (count/mm) at the time of radiological examinations. RESULTS: Of the 104 patients, 47 (45.2%) exhibited a lumbar lesion. There were two types of lumbar disc lesions related to RA: disc narrowing and disc ballooning. The Lansbury index of patients with the most severe lesions was significantly higher than that of patients with less severe lesions (p<.01). The frequency of lumbar involvement also increased as the number of affected peripheral joints increased, and Ochi's classification appeared to be useful in predicting the occurrence of lumbar lesions. CONCLUSION: Of 104 patients, 47 (45.2%) exhibited abnormalities on X-ray films and MRI. There were two types of disorders, disc narrowing and disc ballooning. Both the Lansbury index and Ochi's classification reflected the severity of lumbar lesions in RA patients.
17894004 Heat-shock protein 65 autoantibodies are differently associated with early atherosclerosis 2007 Jun The aim of this study was to examine whether heat-shock protein (HSP)-65 autoantibodies are associated with early atherosclerosis in rheumatoid arthritis (RA). Intima-media thickness (IMT) was measured in the carotid arteries of 100 RA patients and 69 control subjects. The IMT was evaluated on both carotid arteries in the common carotid, bifurcation, and internal arteries. Every patient underwent anti-HSP-65 antibody evaluation. Anti-HSP-65 antibodies were not more prevalent among patients compared with controls. Among controls, patients having "positive" anti-HSP-65 tended to have increased carotid artery IMT compared with "negative" patients, whereas among RA patients the opposite association was noted, and positive patients had significantly decreased carotid bifurcation IMT than negative patients without elevated levels of anti-HSP-65. As opposed to the association with cardiovascular diseases and atherosclerosis of anti-HSPs in the general population, among RA patients anti-HSP-65 cannot be regarded as associated with early atherosclerosis.
16899498 Very recent onset rheumatoid arthritis: clinical and serological patient characteristics a 2007 Feb OBJECTIVES: Despite early recognition and disease modifying anti-rheumatic drug (DMARD) treatment, a sizable proportion of early rheumatoid arthritis (RA) patients show radiological progression. This study was performed to determine the frequency of erosive arthritis and the pace of radiological progression in an inception cohort of patients with very early RA (
17083757 ACR remission criteria and response criteria. 2006 Nov As additional DMARDs have been added to the armamentarium of rheumatologists over the last 60 years, the approach to the treatment of rheumatoid arthritis has changed. Many clinical studies now are geared toward evaluating the concept of eradicating inflammation as a method to seek the elusive goal of sustained remission in RA. One of the first descriptions of remission in 'RA' was by Short et al in 1948, when he documented the natural progression of the disease. Since that time, various criteria have been developed to define RA remission utilizing clinical, radiographic, and laboratory measures. The most stringent of criteria is the American College of Rheumatology Remission Criteria, developed in 1980, which consists of clinical symptoms and signs of inflammation including fatigue, joint pain, morning stiffness, joint tenderness, joint swelling, and erythrocyte sedimentation rate (ESR). Several reports have compared ACR remission criteria to Disease Activity Score (DAS) values to identify equivalent DAS remission values, and these have been extrapolated to modified versions of the DAS, the Simple Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). The ACR remission criteria and the response measures were not designed for use as the target or goal for the clinical management of individual RA patients in routine clinical practice. Nevertheless, rheumatologists yearn for the eradication of inflammation in all RA patients, and attaining remission may be achievable in the future.