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ID PMID Title PublicationDate abstract
17309888 Concurrent gene therapy strategies effectively destroy synoviocytes of patients with rheum 2007 May Objectives. Rheumatoid arthritis (RA) is characterized by the chronic inflammation of the synovial joints resulting from the hyperplasia of synovial cells and the infiltration of lymphocytes, macrophages and plasma cells. Currently, the aetiology of RA is not known, and new treatment modalities are needed to prevent the disease progression. Apoptosis induction of synovial cells through the use of death ligands has been explored as a treatment modality for RA. Thus, the primary objective of this study was the testing of the efficacy of adenovirus delivery of human TRAIL (Ad5hTRAIL) for the treatment of patients with RA. Methods. Primary synovial cell cultures were established from eight patients with RA. Adenovirus permissiveness of synovial cells was determined by the infection of synoviocytes with adenovirus vector encoding green fluorescent protein (AdEGFP). TRAIL sensitivity of synoviocytes was assessed through the infection with Ad5hTRAIL vector using Live/Death Cellular Viability/Toxicity kit from Molecular Probe. TRAIL receptor profiles of synoviocytes were revealed by real-time RT-PCR assays followed by flow cytometric analyses. Results. While the presence of TRAIL death receptors were necessary for the induction of cell death, high levels of TRAIL-R4 decoy receptor expression on surface were correlated with TRAIL resistance. A DcR2 siRNA approach in combination with Ad5hTRAIL infection eliminated apoptosis-resistant RA synovial fibroblasts. Conclusion. Because a DcR2 siRNA approach in combination with Ad5hTRAIL infection exterminated RA synoviocytes to a greater extent than Ad5hTRAIL alone, the modulation of TRAIL receptor expression might be a new gene therapy strategy to sensitize RA synoviocytes to TRAIL.
17158824 Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis. 2007 May OBJECTIVE: To assess mortality in patients with rheumatoid arthritis (RA) treated with tumour necrosis factor (TNF) inhibitors, compared with a standard RA population. METHODS: Patients were recruited from a regional register, which includes over 90% of patients with RA treated with TNF blockers in the area in 1999 or later, and a local community-based cohort of patients with RA, established in 1997. Of a total of 1430 patients in the combined cohort <80 years old, 921 received treatment with TNF inhibitors during the study period. The total cohort was linked with the national register for cause of death. Overall mortality in those treated versus those not treated with TNF blockers was estimated using standardised mortality ratios and time-dependent Cox proportional hazards. RESULTS: There were 188 deaths per 7077 person-years at risk in the total cohort. Controlling for age, sex, disability and baseline comorbidity, the adjusted HR for death was 0.65 (95% CI 0.46 to 0.93) in those treated with anti-TNF versus those not treated. The effect was significant in women (HR = 0.52, 95% CI 0.33 to 0.82) but not in men (HR = 0.95, 95% CI 0.52 to 1.71). CONCLUSION: After adjusting for disease severity, treatment with TNF inhibitors was found to be associated with a reduced mortality in women but not men with RA. These findings are compatible with a critical role for inflammation in RA-associated premature mortality.
16793844 Patterns of cardiovascular risk in rheumatoid arthritis. 2006 Dec BACKGROUND: Although it is known that rheumatoid arthritis is associated with an increased risk of cardiovascular disease (CVD), the pattern of this risk is not clear. This study investigated the relative risk of myocardial infarction, stroke and CVD mortality in adults with rheumatoid arthritis compared with adults without rheumatoid arthritis across age groups, sex and prior CVD event status. METHODS: We conducted a cohort study among all residents aged >or=18 years residing in British Columbia between 1999 and 2003. Residents who had visited the doctor at least thrice for rheumatoid arthritis (International Classification of Disease = 714) were considered to have rheumatoid arthritis. A non-rheumatoid arthritis cohort was matched to the rheumatoid arthritis cohort by age, sex and start of follow-up. The primary composite end point was a hospital admission for myocardial infarction, stroke or CVD mortality. RESULTS: 25 385 adults who had at least three diagnoses for rheumatoid arthritis during the study period were identified. During the 5-year study period, 375 patients with rheumatoid arthritis had a hospital admission for myocardial infarction, 363 had a hospitalisation for stroke, 437 died from cardiovascular causes and 1042 had one of these outcomes. The rate ratio for a CVD event in patients with rheumatoid arthritis was 1.6 (95% confidence interval (CI) 1.5 to 1.7), and the rate difference was 5.7 (95% CI 4.9 to 6.4) per 1000 person-years. The rate ratio decreased with age, from 3.3 in patients aged 18-39 years to 1.6 in those aged >or=75 years. However, the rate difference was 1.2 per 1000 person-years in the youngest age group and increased to 19.7 per 1000 person-years in those aged >or=75 years. Among patients with a prior CVD event, the rate ratios and rate differences were not increased in rheumatoid arthritis. CONCLUSIONS: This study confirms that rheumatoid arthritis is a risk factor for CVD events and shows that the rate ratio for CVD events among subjects with rheumatoid arthritis is highest in young adults and those without known prior CVD events. However, in absolute terms, the difference in event rates is highest in older adults.
17678834 A practical guide to scoring a Multi-Dimensional Health Assessment Questionnaire (MDHAQ) a 2007 Aug The American College of Rheumatology Core Data Set for rheumatoid arthritis (RA) includes 3 measures which are found on a patient self-report questionnaire, physical function, pain, and patient estimate of global status. These measures are included in all clinical trials, but not assessed at most encounters in standard rheumatology care. Rheumatologists may have experience with lengthy research questionnaires in clinical trials and other clinical research, which (appropriately) are regarded as relatively cumbersome research tools and do not contribute to clinical care. A format of a questionnaire known as the multidimensional health assessment questionnaire (MDHAQ) has been developed for standard rheumatology care to contribute to rheumatology clinical care in daily practice. The 3 scores for physical function, pain, and global status can be "eyeballed" in a second or two and formally scored into a composite index known as rheumatology assessment patient index data (RAPID) in about 10 seconds. This chapter provides a brief tutorial designed to instruct rheumatologists and their staffs regarding how to use and score the MDHAQ and RAPID in standard clinical care.
16786162 Resistance to endoplasmic reticulum stress is an acquired cellular characteristic of rheum 2006 Jul Synoviolin is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase which plays a critical role in ER-associated degradation (ERAD). We found that Synoviolin is a novel causative factor for rheumatoid arthritis (RA), which is especially up-regulated in proliferating synovial cells in the disease. We attempted to examine the role of Synoviolin in ER stress-induced apoptosis and proliferation of synovial cells. RA synovial cells (RSCs) were refractory to ER stress-induced apoptosis compared with HEK293 or HeLa cells. RSCs were also more resistant to the apoptosis than synovial cells from osteoarthritis patients, significantly. Down-regulation of Synoviolin by siRNA increased the susceptibility to ER stress-induced apoptosis in RSCs. Knock-down of Synoviolin by siRNA did not only induce apoptosis of RSCs but also inhibited their proliferation in vitro. These data suggest that RSCs are extraordinarily refractory to ER stress-induced apoptosis, and we termed this special property 'hyper-ERAD'. Since Synoviolin is overexpressed in RSCs, and is known to play a critical role in the ERAD system as E3 ubiquitin ligase, hyper-ERAD is likely to present in these cells. Subsequently, the hyper-ERAD may cause synovial hyperplasia through its anti-apoptotic effect in RA. Further analyses are necessary to address this point, however, resistance to ER stress-induced apoptosis, or hyper-ERAD is a noteworthy new cellular characteristic of RSCs.
19041080 Imaging as a follow-up tool in clinical trials and clinical practice. 2008 Dec Imaging is key to the objective analysis of status in joint diseases. X-ray is the mainstay of imaging in both osteoarthritis (OA) and rheumatoid arthritis (RA) due to its accessibility, low cost and very good reproducibility. Also, considerable experience has been gathered in the evaluation of X-rays with the Sharp score in RA and the Kellgren-Lawrence score in OA. X-rays only show structural changes and, in comparison with magnetic resonance imaging (MRI), the detection of erosions on X-ray is delayed for more than 1 year. More advanced imaging by both MRI and ultrasound (US) may add to clinical examinations by showing signs of RA activity. US is by far the easiest modality to apply in a rheumatology outpatient setting, and is becoming an everyday diagnostic tool in many clinics. The definitions and standards for US are still being tested and need further work before application in longitudinal settings is possible. Reproducibility is better with MRI, but this examination is time-consuming, both in the acquisition phase with the patient and also for interpretation and scoring by the examiner. The latter issue seems to be overcome by computer-assisted diagnostics using algorithms for automatic evaluation. With technical developments and increasing knowledge regarding both MRI and US, both of these modalities may be of value in the evaluation of rheumatology patients.
18050379 The Italian registry of aggressive rheumatoid arthritis -- the GIARA project. 2007 Dec OBJECTIVE: In 1999, the Italian Society of Rheumatology started a project to determine the prevalence and clinical characteristics of aggressive rheumatoid arthritis (ARA). METHODS: For 1 year, all patients with RA for > 5 years and referred to participating centers were entered in a registry and classified as having ARA if they fulfilled the following criteria: 10 swollen joints for at least 6 weeks, positive rheumatoid factor (RF), and at least one bone erosion (if disease duration of 2 years); (a) RF-positive and having 10 swollen joints or at least one newly eroded joint, or (b) if RF-negative, having 10 swollen joints and at least one newly eroded joint (if disease duration > 2 to < 5 years). RESULTS: The 94 participating centers enrolled 1218 patients with RA, 1130 of whom had enough data to be classified as ARA (29.0%) or non-ARA (71.0%). The frequency of ARA was 15% in the 2-year group and 63% in the > 2 to < 5-year group, but 35% of the patients in the 2-year group had erosions. Bone erosions were associated with disease duration, a Health Assessment Questionnaire value > 1.5, female sex, and RF positivity. Conditions other than RA were recorded in about 50% of the patients, and only 30% 40% were taking disease modifying antirheumatic drugs. CONCLUSION: In an Italian RA population, the GIARA (Gruppo Italiano Artrite Reumatoide Aggressiva) criteria for ARA were met by 15% of the patients with disease duration of 2 years, but erosions were seen in 35%. Upon referral, most of the RA patients were inadequately treated and had other conditions.
19061594 Development of new-onset psoriasis in a patient receiving infliximab for treatment of rheu 2008 Sep 15 Infliximab is a chimeric monoclonal antibody that selectively blocks tumor necrosis factor-alpha (TNF-alpha). It is indicated for the treatment of numerous inflammatory diseases, including rheumatoid arthritis, Crohn disease, ulcerative colitis, ankylosing spondyilitis, and psoriatic arthritis. Infliximab has also been shown to be a well tolerated and highly effective treatment for psoriatic skin lesions. We report an interesting case of unexpected, new-onset psoriasis in a patient on infliximab for rheumatoid arthritis.
17911422 Nitric oxide signaling triggered by the rheumatoid arthritis shared epitope: a new paradig 2007 Sep Many immune-mediated diseases are associated with particular MHC class I or class II alleles. In rheumatoid arthritis (RA-shared), the vast majority of patients possess HLA-DRB1 alleles encoding a shared epitope, which is a five-amino acid sequence motif in positions 70-74 of the HLA-DRbeta chain. The mechanistic basis for this association is unknown. Here we discuss recent evidence suggesting that the shared epitope may act as an allele-specific ligand that triggers increased nitric oxide (NO) production in opposite cells with resultant immune dysregulation. We propose that by doing that, the RA-shared shared epitope may form an unintended bridge between the innate and adaptive immune systems, thereby allowing aberrant signaling events that could trigger disease.
16882590 Infectious causes of death in patients with rheumatoid arthritis: an autopsy study. 2006 Jul OBJECTIVE: To study mortality from infections and accuracy of pre-mortem diagnoses in patients with rheumatoid arthritis (RA) autopsied during a 40-year period. METHODS: We investigated infectious causes of death, findings at autopsy, and clinicians' estimation of cause of death in 369 consecutively autopsied RA and 371 autopsied non-RA patients with same sex, age at death, and year of autopsy. We also compiled clinical features of RA patients from medical records available and examined the association between these and infectious causes of death. RESULTS: Deaths from any infection were more frequent in RA (36%) than in non-RA (26%) patients. In both groups, respiratory and urinary tract infections were the most common infectious causes of death. More RA patients died from urinary tract infections than non-RA patients. In approximately half of the patients in both groups, infection as a cause of death was unrecognized before death, with no major change occurring over the 40-year study period. CONCLUSIONS: Infections, especially respiratory and urinary tract infections, are frequent causes of death in RA patients. The high proportion of undiscovered infections as a cause of death highlights the diagnostic difficulty. With a decreasing number of autopsies being performed at present, greater numbers of infections may be under-reported.
18983663 The association between C-reactive protein and the likelihood of progression to joint repl 2008 Nov 4 BACKGROUND: This study sought to evaluate the association between systemic inflammation as measured by C-reactive protein and total joint replacement and the association between change in CRP status (low, < or = 10 mg/L and high, >10 mg/L) measured over one year and total joint replacement in patients diagnosed with rheumatoid arthritis. METHODS: A cohort of patients was selected from The Health Improvement Network (THIN) dataset of anonymised patient-level data from UK general practice with a confirmed chronic rheumatic diagnosis. Surgery-free survival was evaluated using Cox proportional hazards regression models (CPHM). RESULTS: 2,421 cases had at least one CRP measurement of which 125 cases (5.2%) had at least one major joint replacement. In CPHM, each additional unit increase in log mean CRP (range 1 to 6) was associated with a hazard ratio (HR) for major orthopaedic surgery of 1.36 (95% CI 1.10 to 1.67; p = 0.004), after controlling for age at first rheumatoid presentation and average body mass index over the same observation period. Repeated CRP observations around one year apart were recorded in 1,314 subjects. After controlling for confounding factors, in cases whose CRP remained high (>10 mg/L), the HR for joint replacement increased more than two-fold (p = 0.040) relative to cases whose CRP remained low. In patients whose CRP increased from low to high, the HR was 1.86 compared to those who remained in a low state (p = 0.217). By comparison, among those subjects whose CRP was reduced from a high to low state, the hazard ratio was more than halved (1.46) from to those who remained high (p = 0.441). Although underpowered, the trend evident from CRP change corroborates the association of TJR progression with mean CRP. CONCLUSION: CRP level predicts progression to major joint replacement after standardisation for relevant risk factors as did change in CRP status between low and high states observed over one year.
17216678 Patient self-administered joint tenderness counts in rheumatoid arthritis are reliable and 2007 Jan OBJECTIVE: To examine whether self-assessment of tender and swollen joints by patients with rheumatoid arthritis (RA) can be used to evaluate changes in disease activity instead of joint counts by physicians. METHODS: Eighty-two patients with RA taking part in controlled studies were recruited for investigation. The patient's self-assessment of joint tenderness and swelling was completed both before and 30 minutes after examination by a physician. Examinations of tender and swollen joints by a rheumatologist were performed at baseline and 3 months later. The correlations and verification of agreement of these clinical assessments were analyzed. RESULTS: Within-patient and patient-physician correlations for joint tenderness counts were high (r = 0.96 and 0.78, respectively). Patient-physician correlation for joint swelling counts was still significant, although much lower (r = 0.34). Patients' and physicians' estimations of the change in disease activity over 3 months did not differ (p > 0.76 for all comparisons). CONCLUSION: Joint tenderness counts were consistent when comparing intra-patient and patient-physician assessments, while joint swelling counts were poorly correlated. Patient and physician assessments of change over 3 months were parallel and similar for joint tenderness count. Self-administered tender joint counts might be a useful tool to evaluate the response to therapy in RA.
16456819 Low-field compact magnetic resonance imaging system for the hand and wrist in rheumatoid a 2006 Mar PURPOSE: To investigate the feasibility of an originally developed compact MRI system for evaluating rheumatoid arthritis (RA), and determine its advantages and disadvantages as an imaging modality for evaluating RA. MATERIALS AND METHODS: We prospectively studied 13 healthy controls with no clinical symptoms of arthritis, and 13 patients with hand and wrist pains (including pain from RA) with a 0.2 T permanent-magnet compact MR imager. All MR images were obtained while the subjects were in a sitting position. Coronal three-dimensional spin-echo T1-weighted images and coronal two-dimensional short tau inversion recovery (STIR) images were obtained with image matrix = 256 x 128 and field of view (FOV) = 20.48 cm. Plain radiograph findings and MRI findings of patients were compared. RESULTS: In three of the patients with suspected early RA (N = 7), early RA was evaluated based on STIR images. All RA patients showed morphologic or signal intensity changes that allowed an evaluation of RA from MR findings. Four of five RA patients showed high signal intensity on STIR images in the wrist, proximal interphalangeal (PIP) joint, or metacarpophalangeal (MCP) joint that suggested synovitis. Multiple erosions in the hand and wrist were seen in four RA patients, with low signal intensity on T1-weighted images. CONCLUSION: RA was correctly evaluated, and early RA could be identified with the compact MRI system. However, the current system has limitations, such as the nonselective STIR sequence used and magnetic field inhomogeneity.
17984578 [NF-kappaB as a therapeutic target of rheumatoid arthritis]. 2007 Oct Nuclear factor kappa B (NF-kappaB) is an inducible transcription factor that is activated through intracellular signal transduction pathways. Its target genes include those that are responsible for immuno-inflammatory responses, apoptosis inhibitors, growth promoting factors, virus-encoded proteins involved in viral replication, and self-regulatory proteins for NF-kappaB actions. Thus, it has been reported that NF-kappaB plays major roles in the pathogenesis of cancer, leukemia, autoimmune diseases such as rheumatoid arthritis, and AIDS. On the other hand, it has been revealed that some drugs that are effective in the treatment of rheumatoid arthritis have actually inhibitory activities of NF-kappaB actions. In this review, we have attempted to analyze various pathological steps of rheumatoid arthritis especially by depicting the steps that involve NF-kappaB. We also discuss possible therapeutic strategies with NF-kappaB as a major target.
17225486 Rheumatoid arthritis in a military aviator. 2007 Jan Rheumatoid arthritis is a chronic inflammatory condition whose pathogenesis is determined partially by genetic and environmental factors. Without treatment, 20 to 30% of individuals with this condition will become permanently disabled in a few years. Rheumatoid arthritis and its potential complications can cause significant disability and could seriously affect the performance of an aviator. Traditionally, disease-modifying anti-rheumatic drugs (DMARD) and biologics have not been used until disease progression occurs, but they recently have been added earlier in the course of disease for a more aggressive approach to treatment. It has been shown to significantly reduce the number of affected joints, pain, and disability. This newer treatment regimen has helped a military pilot continue his aviation career. We present the case of an experienced designated military pilot who was diagnosed with rheumatoid arthritis. He was initially treated early with a DMARD and biologic medication. He has remained in remission and currently only uses etanercept (biologic medication) and a non-steriodal anti-inflammatory drug to control his disease. He has responded favorably to therapy and has few limitations. Due to his positive response to treatment, the aviator was granted military aeromedical waivers for rheumatoid arthritis and chronic medication use.
18678568 Functional thumb orthosis for type I and II boutonniere deformity on the dominant hand in 2008 Aug OBJECTIVE: To evaluate the effectiveness of a functional thumb orthosis on the dominant hand of patients with rheumatoid arthritis and boutonniere thumb. METHODS: Forty patients with rheumatoid arthritis and boutonniere deformity of the thumb were randomly distributed into two groups. The intervention group used the orthosis daily and the control group used the orthosis only during the evaluation. Participants were evaluated at baseline as well as after 45 and 90 days. Assessments were preformed using the O'Connor Dexterity Test, Jamar dynamometer, pinch gauge, goniometry and the Health Assessment Questionnaire. A visual analogue scale was used to assess thumb pain in the metacarpophalangeal joint. RESULTS: Patients in the intervention group experienced a statistically significant reduction in pain. The thumb orthosis did not disrupt grip and pinch strength, function, Health Assessment Questionnaire score or dexterity in either group. CONCLUSION: The use of thumb orthosis for type I and type II boutonniere deformities was effective in relieving pain.
16493242 Coronary artery disease is more severe in older persons with rheumatoid arthritis than in 2006 Mar We investigated the severity of coronary artery disease (CAD) diagnosed by coronary angiography performed because of suspected CAD in 102 persons, mean age 68 years, with rheumatoid arthritis (RA) and in 102 age-matched and sex-matched persons. CAD was diagnosed by coronary angiography in 80 of 102 persons (78%) with RA and in 79 of 102 persons (77%) without RA (P not significant). Three-vessel CAD was present in 31 of 102 persons (30%) with RA and in 8 of 102 persons (8%) without RA (P < 0.001). Coronary revascularization was performed in 71 of 102 persons (70%) with RA and in 23 of 102 persons (23%) without RA (P < 0.001). Older persons with RA with suspected CAD have a higher prevalence of 3-vessel CAD and a higher prevalence of coronary revascularization than age-matched and sex-matched persons with suspected CAD without RA.
15975967 Duration of rheumatoid arthritis influences the degree of functional improvement in clinic 2006 Feb BACKGROUND: Functional capacity is an important outcome in rheumatoid arthritis and is generally measured using the Health Assessment Questionnaire disability index (HAQ). Functional limitation incorporates both activity and damage. Because irreversible damage increases over time, the HAQ may be less likely to show improvement in late than in early rheumatoid arthritis. OBJECTIVE: To determine the relation between sensitivity to change of the HAQ and duration of rheumatoid arthritis in reports of clinical trials. METHODS: Data were pooled from clinical trials that measured responses of HAQ scores at three or six months. The effect size of the HAQ was calculated and linear regression used to predict the effect size by duration of rheumatoid arthritis at group level. Treatment effect was adjusted for by including the effect sizes of pain scores and of tender joint counts as additional independent variables in separate models. Subgroup analysis employed contemporary regimens (methotrexate, leflunomide, combination therapies, and TNF inhibitors) only. RESULTS: 36 studies with 64 active treatment arms and 7628 patients (disease duration 2.5 months to 12.2 years) were included. The effect sizes of the HAQ decreased by 0.02 for each additional year of mean disease duration using all trials, and by 0.04/year in the subgroup analysis (p
16556527 [Evaluation of a new fluorometric immunoassay for the detection of anti-cyclic citrullinat 2006 Mar Anti-cyclic citrullinated antibodies occurrence is a recent serological marker for rheumatoid arthritis. The aim of our study was to evaluate the measurement of these antibodies by a new fluorescent-enzyme immunoassay, called EliA CCP, fully automated onto UniCAP 100. This evaluation reveals correct and shows a within run imprecision of 4.6 to 10.5 % and a between-assay imprecision of 9,5 %. The comparison with an Elisa method (Euroimmun) shows a good correlation of anti-CCP concentrations without any major discrepancy.
19083077 Improvement of the HAQ score by infliximab treatment in patients with RA: its association 2009 We conducted a two-year prospective study to clarify the efficacy of infliximab at improving the health assessment questionnaire (HAQ) score and associated factors in 67 patients with advanced rheumatoid arthritis (RA). All patients were scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2, 6 and every eight weeks thereafter through to week 102, and were fully examined at the time of each infusion. Parameters of disease activity such as the serum level of C-reactive protein (CRP), the serum level of matrix metalloproteinase-3 (MMP-3) and the 28-joint disease activity score (DAS28) were obtained, and the functional capabilities of the patients were assessed using the HAQ score. The serum CRP, the MMP-3, the DAS28(CRP) level, and the mean HAQ score decreased rapidly at two weeks after the start of infliximab treatment (CRP from 3.7 to 0.9 mg/dl, MMP-3 from 362.3 to 192.8 ng/ml, DAS28(CRP) from 5.6 to 3.7, and HAQ score from 1.5 to 0.9). Compared with the baseline values, the mean progression of the modified van der Heijde (vdH)-Sharp score after one year was 4.4 +/- 5.8 (median: 3.0), and that after two years was 3.1 +/- 6.9 (median: 1.0). A 93% reduction in the rate of joint destruction, as measured using the vdH-Sharp score, was estimated after infliximab therapy. Patients with less joint damage (shorter disease duration or lower vdH-Sharp score) regained more of their daily activities. The present study demonstrated the importance of activity control before the progression of irreversible factors, such as joint destruction, for maintaining the functional capacities of RA patients.