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ID PMID Title PublicationDate abstract
15838238 Vascular comorbidity in rheumatoid arthritis: potential mechanisms and solutions. 2005 May PURPOSE OF REVIEW: To summarise recent evidence for elevated risk of coronary heart disease (CHD) in rheumatoid arthritis (RA) and explore explanatory mechanisms and modalities that may lessen such risk. RECENT FINDINGS: Evidence for elevated CHD risk in RA is convincing. On current estimates, individuals who have had RA for several years have around a twofold higher risk for CHD compared with non-RA persons after taking account of most traditional risk factors. Such excess risk appears to be driven by systemic inflammation both directly via its deleterious effects on blood vessels (endothelial dysfunction inclusive of myocardial microvascular abnormalities) and indirectly by its accentuation of multiple risk pathways including lipid abnormalities. Established therapies that lessen RA disease activity and systemic inflammation will likely lessen CHD risk, although there remains considerable scope for more robust studies employing better measures of vascular disease (e.g., carotid intima-media thickening). Other emerging evidence indicates statins may have dual effects in RA, with a modest disease-modifying effect (requiring confirmation) and significant lipid-lowering action. The latter finding is particularly important because extrapolation of data from all statin endpoint trials suggests that the extent of low-density lipoprotein cholesterol reduction may account for most statin clinical benefit. SUMMARY: Systemic inflammation is the major driver for excess vascular comorbidity in RA. Controlling systemic inflammation should lessen vascular risk but complete, long-term suppression of articular inflammation is rarely achieved. Thus, the use of conventional CHD risk reduction strategies, in particular statins, should be considered in patients with RA with prevalent CHD or at elevated risk.
16465654 Subclinical atherosclerosis in rheumatoid arthritis in India. 2006 Feb OBJECTIVE: Patients with rheumatoid arthritis (RA) have high cardiovascular morbidity and mortality as compared to the general population. Indians are also at increased risk of developing early and severe atherosclerotic coronary artery disease. Carotid intima-media thickness as measured by ultrasound is a validated surrogate marker of atherosclerosis. We studied the prevalence of subclinical atherosclerosis in Indian patients with RA. METHODS: Common carotid IMT (CCA IMT) was measured at the level of carotid bifurcation along with fasting lipid profile in 57 RA patients and 45 age and sex matched controls. Values of mean CCA IMT above mean + 2 SD of the control group were defined as abnormal IMT. Variables of disease activity and severity were measured in RA patients. Patients and controls with known traditional cardiovascular risk factors were excluded from the study. Student t test and chi-square test for proportion were used for statistical analysis. A logistic regression analysis was done to find out independent predictors of abnormal IMT. RESULTS: Nineteen RA patients (33.3%) and 2 controls (4.44%) had abnormal IMT values. RA patients had significantly increased mean CCA IMT (0.558 +/- 0.137 mm) as compared to controls (0.416 +/- 0.002 mm; p < 0.0001). Age > or = 42 years, duration of disease > or= 6 years, and tender joint count > or = 5 predicted increased risk of having abnormal CCA IMT in a logistic regression analysis. CONCLUSION: One-third of Indian RA patients had subclinical atherosclerosis. Age and tender joint count were independent predictors of abnormal CCA IMT.
16782731 Citrullination in extra-articular manifestations of rheumatoid arthritis. 2007 Jan BACKGROUND: Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules. METHODS: Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed. RESULTS: Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44%) and nine patients with idiopathic IP (46%). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20%). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use. Rheumatoid nodules were citrulline positive in a majority of cases (70%). CONCLUSION: Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.
16568506 Community-based evaluation of etanercept in patients with rheumatoid arthritis. 2006 Apr OBJECTIVES: Etanercept is one of a new subgroup of biological disease modifying antirheumatic drugs (DMARD) to treat patients with rheumatoid arthritis (RA) who are non-responsive or intolerant to conventional DMARD. We evaluated the effects of etanercept (Enbrel) therapy in patients with RA in community-based clinical practice in Canada. METHODS: Using a cohort design, patients requesting etanercept therapy were stratified into treatment and control arms based upon their individual accessibility to obtain the drug. Patients were interviewed serially during a 12-month period of monitoring. The study measured painful or tender joint count, morning stiffness, pain severity, quality of life measures, medication utilization, health services utilization, and presence of adverse events. RESULTS: The baseline demographic and clinical variables for the treatment group (n = 223) and the control group (n = 208) were similar, except for education, income, and drug plan coverage. In followup, there was greater improvement in most clinical variables in the treatment arm compared to the control arm during the first 6 months, but the magnitude of difference between the 2 groups for some clinical variables decreased or became non-significant during the second 6 months. During the 12 month followup period there were 40 (18%) patient dropouts in the treatment group. CONCLUSION: In a community based setting for the treatment of RA, etanercept can effectively improve the disease state, functional class, work disability, and quality of life during the first 6 months of use. To determine the longterm sustainability of these effects studies with more than 12 months' duration will be required.
15981028 Relationship between bone mineral density and urine level of NTx in rheumatoid arthritis. 2005 We analyzed the relationship between the level of type-I collagen N-telopeptide (NTx) in urine (U-NTx) and bone mineral density (BMD) in patients with rheumatoid arthritis (RA). The subjects were 62 female patients with RA who had experienced the menopause 5 years or more before the study commenced, and who had not been treated for osteoporosis. The mean age of the subjects was 61.6 years and the mean disease duration was 13.3 years. They were classified for global functional status (classes I to IV), and then grouped based on the presence or absence of corticosteroid administration. Bone mineral density (BMD) and U-NTx levels were measured. In the presence of corticosteroid administration (CS group; n = 40), the mean level of U-NTx/creatinine (Cr) was 88.8 nM and the percent young adult mean (%YAM) for BMD was 71.2%. In the no corticosteroid (nCS group; n = 22), the values were 72.1 nM and 78.2%, respectively. The U-NTx/Cr value and %YAM were not significantly different between the CS group and the nCS group. A negative correlation was observed between the U-NTx/Cr value and %YAM in both groups (P = 0.005 and P = 0.0265). No significant difference was observed for the U-NTx/Cr value or %YAM between the CS and nCS groups, in any class. In the CS group, a positive correlation was observed between the U-NTx/Cr value and the total dose of corticosteroid (P = 0.001), and a negative correlation was observed between the %YAM and the total dose of corticosteroid (P = 0.003). These results suggested that preventive medical treatment for osteoporosis is required for RA patients in class III, irrespective of whether they have had corticosteroid administration.
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.
15744650 [Long-term results of resection arthroplasty of the metacarpophalangeal joint in rheumatoi 2005 Feb The metacarpophalangeal arthroplasty in rheumatoid arthritis reported is a modification of the Vainio-Arthroplasty. The main difference of the technique is the fixation of the proximal extensor tendon to the palmar plate, better to the ligamentum metacarpeum transversum profundum. The more flexion of the metacarpophalangeal joint the more reposition of the joint is achieved. The long-term results of 30 arthroplasties of the metacarpophalangeal joint are presented in a prospective study. The cases were followed for 10.5 to 14.5 years (average 11.6 years). Marked release of pain was found in all patients. 75 per cent of the patients reported functional improvement of their hand at a score of "good" or "very good". The postoperative movement was 70 degrees on an average. In summary, the resection arthroplasty of the metacarpophalangeal joints produces very good function and correction of the ulnar deviation and palmar luxation of the MCP-joints. The arthroplasty is a real alternative to the total endoprosthetic replacement of metacarpophalangeal joints in rheumatoid arthritis.
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.
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.
15972909 Souter-Strathclyde total elbow arthroplasty in rheumatoid arthritis: medium-term results. 2005 Jul We present the outcome of 47 Souter-Strathclyde replacements of the elbow with a mean follow-up of 82 months (12 to 129). The clinical results were assessed using a condition-specific outcome measure. The mean total score (maximum 100) before the operation was 47.21 and improved to 79.92 (p < 0.001). The mean pain score (maximum 50) improved from 21.41 to 46.70 (p < 0.001) and the mean functional component of the score (maximum 30) from 11.19 to 18.65 (p < 0.001). There was negligible change in the score for the range of movement although a significant improvement in mean flexion from 124 degrees to 136 degrees was noted (p < 0.001). Revision surgery was required in four patients, for dislocation, wound dehiscence and early infection in one, late infection in two and aseptic loosening in one. The cumulative survival was 75% at nine years for all causes of failure and 97% at ten years for aseptic loosening alone. Our study demonstrates the value of the Souter-Strathclyde total elbow arthroplasty in providing relief from pain and functional improvement in rheumatoid patients.
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.
16298911 Biomarkers for diagnosing and monitoring autoimmune diseases. 2005 Nov The goal of studies of autoimmune disease biomarkers is to identity markers that fluctuate with disease development and severity, but then normalize following successful therapy. The perfect marker could thus serve as a diagnostic tool, as well as a monitoring device for therapeutic drug efficacy. Current biomarker discovery efforts are focused on three groups of proteins reflective of the autoimmune disease process: (1) degradation products arising from destruction of affected tissues, (2) enzymes that play a role in tissue degradation and (3) cytokines and other proteins associated with immune activation. Potential biomarkers for two autoimmune diseases, rheumatoid arthritis and multiple sclerosis, have been described in recent publications. For rheumatoid arthritis, these markers (by group) include (1) aggrecan fragments, C-propeptide of type II collagen and cartilage oligomeric matrix protein, (2) matrix metalloprotease (MMP)-1, MMP-3 and MMP-1/inhibitor complexes and (3) thioredoxin, IL-16 and tumour necrosis factor (TNF)-alpha. For multiple sclerosis, they include (1) neurofilament light protein and glial fibrillary acidic protein, (2) MMP-2 and MMP-9 and (3) TNF-alpha and soluble vascular adhesion molecule-1. The utility of most of these markers is limited by their restriction to relatively inaccessible anatomic sites (synovial or cerebrospinal fluid). Thus, from a practical standpoint, the most useful autoimmune biomarkers will be those measurable in serum or plasma.
16206362 Minimal disease activity for rheumatoid arthritis: a preliminary definition. 2005 Oct Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: * The DAS28 definition places patients in MDA when DAS28 < or = 2.85; * The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0-10) < or = 2; (2) Swollen joint count (0-28) < or = 1; (3) Tender joint count (0-28) < or = 1; (4) Health Assessment Questionnaire (HAQ, 0-3) < or = 0.5; (5) Physician global assessment of disease activity (0-10) < or = 1.5; (6) Patient global assessment of disease activity (0-10) < or = 2; (7) ESR < or = 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.
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.
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.
16498008 Comparison of two types of ulnar component in type-5 Kudo total elbow arthroplasty in pati 2006 Mar The purpose of this study was to assess the long-term results (more than ten years) of two types of cemented ulnar component with type-5 Kudo total elbow arthroplasty in a consecutive series of 56 patients (60 elbows) with rheumatoid arthritis, and to compare the results in elbows above and below a Larsen grade IV. There was no radiolucency around the humeral component. Patients in whom a metal-backed ulnar component and a porous-coated stem were used had better clinical results and significantly less progression of radiolucent line formation around the ulnar component. They also had a significantly better long-term survival than patients with an all-polyethylene ulnar component. The clinical results of arthroplasty using all-polyethylene ulnar components were inferior, regardless of the degree of joint destruction. We conclude that the type-5 Kudo total elbow arthroplasty with cementless fixation of the porous-coated humeral component and cemented fixation of a metal-backed ulnar component is acceptable and well-tolerated by rheumatoid patients.
16877531 The inflammatory reflex and risk for rheumatoid arthritis: a case-control study of human v 2007 Mar Recent data suggest remarkable effects of vagus stimulation (reduction) and vagotomy (exacerbation) on acute inflammation in rats, the so-called "inflammatory reflex". Its role in humans remains unknown. Therefore, the aim was to explore whether surgical vagotomy in humans would affect the risk of a prototype inflammatory disease, rheumatoid arthritis. This was a case-control study. Assessment of the relative risk (RR) of developing rheumatoid arthritis after surgical vagotomy during 1964-2001 in 63,092 prevalent rheumatoid arthritis cases versus 125,404 matched controls from the general population and in 2548 incident rheumatoid arthritis cases versus 24,357 matched controls from the general population, respectively, was done. For comparison, we assessed RRs for hospitalisation for gastric disorders not including vagotomy. Data on exposures and rheumatoid arthritis were retrieved from population-based and prospectively recorded Swedish registers. A pre-rheumatoid arthritis vagotomy was not significantly associated with an increased risk for rheumatoid arthritis (RR = 1.17, 95% CI 0.97 to 1.40). RRs in the same range were observed for several other pre-rheumatoid arthritis gastric conditions that do not include vagotomy (eg, gastric ulcer RR = 1.21, 95% 1.11 to 1.33). Vagotomy has no specific effect on the risk of developing rheumatoid arthritis in humans. Gastroduodenal ulcers occur more often than expected even before the occurrence of rheumatoid arthritis.
16129908 Pro-inflammatory cytokines in rheumatoid arthritis: pathogenetic and therapeutic aspects. 2005 Jun Therapy of rheumatoid arthritis (RA) aims at interfering with the disease process, namely inflammation and destruction of the joints, and thus at preventing long-term disability. Proinflammatory cytokines play a decisive role in the generation of the inflammatory and destructive response. Aside from traditional disease-modifying anti-rheumatic drugs and tumor necrosis factor-blocking agents, a number of targeted therapies are currently in evaluation, such as abatacept (interfering with co-stimulation), rituximab (an anti-B-cell agent) and tocilizumab (an anti-interleukin-6 receptor antibody). In phase II trials, all these agents have resulted in significant clinical improvement, and phase III trials have been partly completed with similar results and are partly on the way. Because none of these agents lead to good clinical responses in all patients and many patients have only relatively low degrees of response, it will still be a challenge to find the best therapeutic paths to combat the "inflammatory house of cards" of RA.