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ID PMID Title PublicationDate abstract
17642241 [Efficacy and adverse events of etanercept in patients with rheumatoid arthritis: reports 2007 Jul Etanercept is a soluble tumor necrosis factor (TNF) receptor fusion protein that binds and inactivates TNF. Since etanercept was just approved in January 2005 in Japan, a strict postmarketing surveillance has been undertaken. In this trial, initial 3,319 patients with rheumatoid arthritis were collected, and the adverse events and efficacy of etanercept were evaluated. The frequency of adverse events were found in 30.9 %, among total patients particularly severe adverse effects in 4.2 %. Among severe adverse events, 83 patients experienced infection. They included 25 patients with bacterial pneumonia. Interstitial pneumonia, pneumocystis jiroveci and tuberculosis were observed in 11 cases (0.3 %), 5 cases (0.2 %) and 2 cases (0.1%), respectively. Patients who received etanercept had a more rapid rate of improvement in disease activity determined by DAS 28 ESR and DAS28 CRP. These improvements continued through 24 months of etanercept exposure. Using the analysis of EULAR response criteria, the good or moderate response in the DAS 28 ESR response and DAS 28 CRP was found in more than 80% of patients with RA.
16766363 Disability and health-related quality of life among patients with rheumatoid arthritis: as 2006 May OBJECTIVE: To study the associations between disability and health-related quality of life (HRQoL), respectively, and radiographic joint damage, disease activity, pain, and depressive symptoms among patients with rheumatoid arthritis (RA). METHODS: Data were collected through questionnaires and clinical examinations at baseline (1997) and at 2 years' follow-up among patients with RA (n = 307). Disability was measured with a validated Dutch questionnaire, derived from the Health Assessment Questionnaire (HAQ), and HRQoL with a validated Dutch version of the RAND-36, using physical (PCS) and mental (MCS) component summary scales. Multivariate linear regression analyses were performed to assess the relationship between disability or HRQoL and radiographic damage, disease activity, pain, and depressive symptoms. RESULTS: Pain, with respect to disability and PCS, and depressive symptoms, with respect to MCS, were more important predictors than radiographic damage and disease activity. CONCLUSIONS: Daily RA practice needs to be broadened by regular assessment of disease burden from the patients' perspectives. Patient-reported measures, such as disability or HRQoL, should be incorporated for monitoring health outcomes of individual patients and for initiating and evaluating therapy.
17586865 The pharmacogenetics of methotrexate. 2007 Oct Methotrexate (MTX) is a cornerstone of therapy for rheumatoid arthritis. However, it is not universally effective and up to one-third of patients fail to respond to treatment, either because of inefficacy or adverse events, although at present it is not possible to predict therapy response accurately. Pharmacogenetics is the study of variability in drug response due to heredity. MTX has a complex intracellular metabolism and acts via a number of key enzymes. This review critically appraises the studies of MTX pharmacogenetics and highlights the need for further work in this area.
17894001 A new target for autoantibodies in patients with rheumatoid arthritis. 2007 Jun Early treatment of rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs can achieve a better disease outcome and reduce the severity of joint damage. The presence of autoantibodies in patient sera can precede onset of the disease and thus be predictive of the development of RA. To date, known autoantibodies in RA are positive in only 50-60% of RA patients at onset of disease and even less before the onset of any RA symptom. The aim of this study was to identify new antibodies that could be useful for the diagnosis of RA using synovial membrane proteins, which represent the best source of candidate RA autoantigens. The humoral reactivity of sera from RA patients was explored using immunoblotting on extracted proteins obtained from synovial membranes from RA after synovectomy or arthroplasty. A new target protein with a molecular weight of 26 kDa was found to be recognized by autoantibodies in RA sera. This protein was identified using MALDI-TOF mass spectrometry and two-dimensional electrophoresis as carbonic anhydrase III with a high level of confidence. In conclusion, this study demonstrates new autoantibodies in RA patients that are directed against carbonic anhydrase III. The sensitivity and specificity of these new autoantibodies for RA have to be further evaluated.
17477800 Recent advances of TNF-alpha antagonists in rheumatoid arthritis and chronic heart failure 2007 May Tumor necrosis factor (TNF)-alpha has been thoroughly investigated and established as a pivotal component of the inflammatory cascade. This review encompasses the safety and efficacy of TNF antagonists in rheumatoid arthritis, the interplay between rheumatoid arthritis and heart failure, as well as presentation of the available preclinical and clinical data discussing the use of anti-TNF therapy in patients with chronic heart failure. There is well-documented evidence for the role of anti-TNF-alpha in rheumatoid arthritis, in contrast to the controversial role of anti-TNF-alpha in heart failure. In animal models and small-scale clinical trials, anti-TNF therapy showed some promise in treating chronic heart failure, whereas larger, multicenter, randomized, placebo-controlled clinical trials (i.e., RECOVER [Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction] and RENAISSANCE [Randomized Etanercept North American Strategy to Study Antagonism of Cytokines]) failed to show a statistically significant difference in composite clinical function score for anti-TNF therapy versus placebo. Future investigation is needed to determine if individualized dosing of anti-TNF therapy is necessary and whether or not treating patients with earlier-stage disease will show a benefit.
17709949 Stress as a risk factor in the pathogenesis of rheumatoid arthritis. 2006 Stress is now recognized as an important risk factor in the pathogenesis of autoimmune rheumatic diseases (i.e. rheumatoid arthritis) by considering that the activation of the stress response system influences the close relationships existing between the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system and the immune system. The stress response results in the release of neurotransmitters (norepinephrine), hormones (cortisol) and immune cells which serve to send an efferent message from the brain to the periphery. Major life events lead to an intense release of stress mediators (large time integral of released neurotransmitters and hormones), whereas in minor life events, only short-lived surges of neurotransmitters and hormones are expected. Therefore, it is suggested that neurotransmitters such as norepinephrine or stress hormones such as cortisol might have different effects on immune/inflammatory responses at high and low concentrations present during short or extended periods of time, respectively. Long-lasting (chronic) stress may lead to proinflammatory effects because no adequate long-term responses of stress axes (anti-inflammatory) are to be expected.
18765428 Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthriti 2009 Feb OBJECTIVES: Magnetic resonance imaging (MRI) bone oedema is an important predictor of bone erosion in rheumatoid arthritis (RA). This study aimed to determine the cellular components of MRI bone oedema, and clarify the relationship between bone erosion and MRI bone oedema. METHODS: Twenty-eight bones from 11 patients with RA undergoing orthopaedic surgery were analysed by quantitative and semi-quantitative immunohistochemistry. Pre-operative contrast-enhanced MRI scans were analysed for bone oedema. RESULTS: The density of osteoclasts was higher in those samples with MRI bone oedema than those without MRI bone oedema (p = 0.01). Other cells identified within bone marrow included macrophages and plasma cells, and these were more numerous in samples with MRI bone oedema (p = 0.02 and 0.05 respectively). B cells were present in lower numbers, but B cell aggregates were identified in some samples with MRI bone oedema. There was a trend to increased RANKL expression in samples with MRI bone oedema (p = 0.09). Expression of RANKL correlated with the number of osteoclasts (r = 0.592, p = 0.004). CONCLUSIONS: The increased number of osteoclasts and RANKL expression in samples with MRI bone oedema supports the hypothesis that bone erosion in RA occurs through activation of local bone resorption mechanisms within subchondral bone as well as through synovial invasion into bone.
18370240 Pharmacogenomics in rheumatoid arthritis. 2008 Rheumatoid arthritis (RA) is a systemic inflammatory arthritis that leads to severe joint damage and is associated with high morbidity and mortality. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs not only relieve the clinical signs and symptoms of RA but also inhibit the radiographic progression of disease. Recently, a new class of disease-modifying medications, the biologic agents, has been added to the existing spectrum of DMARDs in RA. However, patients' response to these agents is not uniform, with considerable variability in both efficacy and toxicity. There are no reliable means of predicting an individual patient's response to a given DMARD prior to initiation of therapy. In this chapter, the current published literature on the pharmacogenomics of traditional DMARDs and the newer biologic DMARDs in RA is highlighted. Pharmacogenomics may help individualize drug therapy in patients with RA in the near future.
17195414 Impact of treatment with infliximab on anticyclic citrullinated peptide antibody and rheum 2006 Nov OBJECTIVE: To investigate the impact of infliximab treatment on anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) levels in patients with rheumatoid arthritis (RA). METHODS: Sera from 33 RA patients receiving infliximab and disease modifying antirheumatic drugs were tested for anti-CCP antibody, IgA-, IgG- and IgM-RF using a commercially available semiquantitative ELISA at baseline, 30 and 54 weeks after treatment. RESULTS: The serum levels of anti-CCP antibody and IgA-RF decreased significantly after 30 weeks (P = 0.002 and 0.024); however, the decrease was not significant at week 54 (P = 0.147 and 0.207). The decrease in IgG-RF level was not significant at 30 and 54 weeks (P = 0.059 and 0.097). IgM-RF levels, however decreased significantly at 30 and 54 weeks (P = 0.002 and 0.004). A strong correlation between anti-CCP and IgA-, IgG- and IgM-RF was observed at baseline (r(s) = 0.48, 0.43, 0.65, P = < 0.05) and after infliximab treatment at 30 (r(s) = 0.45, 0.46, 0.62, P = < 0.05) and 54 (r(s) = 0.49, 0.45, 0.60, P = < 0.05) weeks. CONCLUSION: Treatment with infliximab results in decreased anti-CCP antibody and IgA-RF early in the course of therapy that is not sustained. IgM-RF declines and remains decreased for at least 54 weeks. Investigations in larger cohorts of RA patients (especially early RA) with longer follow-up are needed to assess the impact of specific therapeutic interventions on anti-CCP antibody and RF levels and the relationship of their levels to disease activity.
17694810 Health care in patients with primary Sjogren's syndrome. 2007 The aim of the present study was to define more accurately the necessary health care in patients with the primary Sjogren's syndrome and to compare it to those necessary for patients with another autoimmune disease--rheumatoid arthritis without a concomitant Sjogren's syndrome (Tab. 1, Ref. 5). Full Text (Free, PDF) www.bmj.sk.
17080517 CD64 on neutrophils is a sensitive and specific marker for detection of infection in patie 2006 Dec OBJECTIVE: In inflammatory diseases, differentiation between infection and disease flares is often clinically difficult because of similar signs and symptoms, such as fever and elevation of inflammatory markers. In rheumatoid arthritis (RA), infection is not only one of the major complications but also one of the frequent causes of death. Use of biologic agents such as tumor necrosis factor-a blockers has been reported to increase the incidence of tuberculosis or opportunistic infections. We examined the utility of CD64 (FcgRI) expressed on neutrophils as a marker for detection of infection complicated with RA. METHODS: We measured the expression level of CD64 per neutrophil quantitatively by flow cytometry in 279 samples from 237 patients with RA with various levels of disease activity or types of infection, and in 52 samples from 36 controls including subjects with infection. RESULTS: CD64 expression was significantly higher among RA patients with infection (median 4156 molecules per neutrophil, interquartile range 2583-8587) than in those without infection (884, IQR 670-1262) (p < or = 0.001). The sensitivity of CD64 on neutrophils for the diagnosis of infection (using a cutoff value of 2000 molecules per cell) was 92.7% and specificity was 96.5%. CD64 expression was not affected by the disease activity of RA or the use of corticosteroids, disease modifying antirheumatic drugs, and biologic agents. CD64 was upregulated in infection by bacteria, viruses, fungi, and mycobacteria. CONCLUSION: Our results suggest that quantitative measurement of CD64 expression on neutrophils can be used as a sensitive and specific marker to detect infection complicating RA.
18472732 [Diagnosis and treatment of rheumatoid vasculitis and other systemic complications of rheu 2008 Mar 19 Rheumatoid arthritis is a systemic disease that can potentially affect any organ. If the articular manifestations are central to the disease; skin, ophthalmic, neurological, cardiac, pulmonary as well as renal manifestations are well recognized, the latter particularly in the context of a secondary amyloidosis. Although incidence of extraarticular manifestations appears to decrease, likely a result from our more aggressive and early management of rheumatoid arthritis, their consequences remain severe in terms of morbidity and mortality, and their treatments complicated. The new biological therapies seem to be a promising alternative to current therapies, such as cyclophosphamide and high dose prednisone, even if evidences are still limited.
17696284 Causes of death in patients with rheumatoid arthritis: comparison with siblings and matche 2007 Aug OBJECTIVE: Survival of patients with rheumatoid arthritis (RA) is reduced when compared to the general population. We assessed differences in causes and age of death between patients with RA and their siblings. Comparisons were also made with a control group of subjects with lower limb osteoarthritis (OA). METHODS: A population of 257 patients with RA studied in 1991 was compared to 371 of their same-sex siblings and 485 patients with hip and knee OA who were also attending the department at this time. Death certificates were obtained and compared. RESULTS: Among patients with RA, 54% (139/257) were deceased, compared to 28% (105/371) of the siblings and 32% (154/485) of OA patients (RA vs siblings or OA, p < 0.05). There were more deaths due to ischemic heart disease (IHD) in both the RA and OA groups compared to those expected; ratio observed/expected, 1.66 (95% CI 1.01, 2.79) and 1.96 (95% CI 1.21, 3.25), respectively, but not for siblings: observed/expected = 1.05 (95% CI 0.53, 2.08). There was a significant deficit in cancer related deaths in RA patients, observed/expected = 0.62 (95% CI 0.36, 1.03). CONCLUSION: Significantly more patients with RA had died than in either of the comparator populations. RA and OA patients died more frequently of IHD than the siblings. The RA population had a 40% reduced rate of cancer related deaths than expected and compared to their siblings.
17426976 Serum pro-matrix metalloproteinase-3 as an indicator of disease activity and severity in r 2007 Jun Matrix metalloproteinase-3 (MMP-3) production increases in rheumatoid arthritis (RA) and has been proposed as a marker of disease activity and joint damage. The aim of this cross-sectional study is to examine the usefulness of serum proMMP-3 as an indicator of disease activity and severity in comparison with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum proMMP-3 was measured by a quantitative ELISA in 85 RA patients and 70 healthy subjects. Clinical and laboratory measures of disease activity and severity were obtained. Radiological joint damage was assessed by the method of Larsen. Serum proMMP-3 was significantly higher in RA patients than that in the healthy subjects. The active RA patients had significantly higher serum proMMP-3 than the inactive patients. Serum proMMP-3 was significantly correlated with some parameters of disease activity including swollen joints count, proximal interphalangeal joint score, morning stiffness, and Health Assessment Questionnaire; however, ESR and serum CRP were better correlated with all indicators of the disease activity than proMMP-3. The analysis of receiver operating characteristic supported that ESR and CRP had higher performance for reflection of activity compared to proMMP-3. There were no significant associations among Larsen score and proMMP-3, ESR, and CRP. Our results suggest that the cross-sectional measurement of serum proMMP-3 could not give additional information about RA disease activity compared to ESR and CRP, and could not give any information about joint damage.
17170055 Ultrasonographic measurement of the median nerve in patients with rheumatoid arthritis wit 2007 Jun OBJECTIVES: Ultrasonography (US) has shown increased cross-sectional area of the median nerve in carpal tunnel syndrome (CTS). Knowledge of the normal distribution of the areas is a prerequisite to evaluate pathology. Presently, the distribution of cross-sectional areas of the median nerve was explored in patients with rheumatoid arthritis (RA). METHODS: The median nerves of patients with RA having no symptoms or signs of CTS were examined with bilateral US at the entrance of the carpal tunnel. RESULTS: A total of 154 patients with RA were included. The median nerve was divided in 11.7% of the hands. The mean (SD) cross-sectional areas of the undivided median nerves were not significantly different on either sides (8.3 (1.5) mm(2) on the right side and 8.3 (1.4) mm(2) on the left side). The areas of the examined 308 median nerves ranged from 5.0 to 12.8 mm(2), with the 97.5 centile being 11.1 mm(2). Areas >10.0 mm(2) were found in 10% of the patients. CONCLUSIONS: The mean cross-sectional areas of the median nerve in patients with RA were similar to those reported in healthy controls. However, 10% of the patients had values that overlap with areas commonly reported in patients with mild idiopathic CTS.
16941197 Anxiety and depression in patients with rheumatoid arthritis. 2007 Jun Rheumatoid arthritis (RA) mostly follows a painful, progressively disabling course, and individuals with RA experience more psychological distress than healthy individuals. The objective of the present study is to examine the prevalences of accompanying anxiety and depression in RA cases. The study included 82 RA cases and 41 age- and sex-matched healthy volunteers as the control group. Psychiatric examinations of all cases of the patient and control groups were performed according to DSM-IV criteria. Hamilton Anxiety Scale or Hamilton Depression Scale was applied to those who were found to have anxiety or depression. Total prevalence of anxiety, depression, and mixed anxiety-depressive disorder was found to be 70.8% (n=58) in the patient group and 7.3% (n=3) in the control group, and the difference was significant (p<0.001). Of the RA patients, 41.5% (n=34) was found to have depression, 13.4% (n=11) anxiety, and 15.9% (n=13) mixed anxiety-depressive disorder. The disease duration in patients with anxiety was shorter than the RA patient with depression (p<0.05). The disease duration was positively correlated with the degree of depression and negatively correlated with the degree of anxiety (r=0.341, p<0.05; r=-0.642, p<0.05, respectively). The results of our study suggest that prevalences of anxiety and mainly depression, increase in RA cases. When the clinical picture in RA cases becomes complicated with anxiety or depression, some problems at patients' adaptation and response to treatment may be possible. RA cases should be monitored for accompanying anxiety or depression during follow-up.
16511918 Short-term outcome after anti-tumor necrosis factor-alpha therapy in rheumatoid arthritis: 2006 Mar OBJECTIVE: To evaluate the Disease Activity Score (DAS) using various aggregated dimensions to quantify treatment outcome in patients with rheumatoid arthritis (RA), in order to determine the best instrument to be used as an endpoint that indicates good response in terms of EULAR response criteria and DAS28 remission criteria, and which satisfies the demands of clinical rheumatology. METHODS: Using raw data for each patient subjected to anti-tumor necrosis factor-a therapy (81 patients), before and 6 months after treatment, DAS28 was calculated 4 times using the standard equation, as follows: (1) DAS 1 (the standard DAS28): tender joint count (TJC), swollen joint count (SJC), patient global assessment (PGA), erythrocyte sedimentation rate (ESR); (2) DAS 2: TJC, SJC, PGA, C-reactive protein (CRP); (3) DAS 3: TJC, SJC, physician global assessment (PhGA), ESR; and (4) DAS 4: TJC, SJC, PhGA, CRP. Disease activity was identified if DAS score exceeded 5.1. A clinically significant response was recorded if there had been improvement of > 1.2 of the DAS score. RESULTS: DAS 2, DAS3, and DAS4 were superior to the current DAS score used for assessment of RA activity (effect size differences were -0.35, -0.13, and -0.48, respectively). Assessment of disease activity using TJC, SJC, PhGA, and CRP was the best tool to assess response to therapy. ESR was marginally superior to CRP in its sensitivity to monitor disease activity changes (effect sizes 1.08 and 1.03, respectively). CONCLUSION: These results suggest that self-report indices on their own, such as PGA and pain score, are inadequate indicators of disease activity. The DAS might profitably be amended by one or 2 continuous measures for better quantification of the degree of improvement of patients on a given therapeutic modality. Using PhGA and CRP instead of PGA and ESR, respectively, in the DAS equation discriminated better between different patients' responses than the traditional DAS score.
19011878 [Project REMISSION(PLUS): clinical and radiological remission : new treatment goals in the 2008 Dec In a large number of patients with rheumatoid arthritis (RA), chronic inflammatory processes cause joint changes and loss of function even in the early stages of disease. Early, targeted use of disease-modifying antirheumatic drugs [DMARDs and TNF-alpha blockers ("biologicals")] can significantly reduce the risk of aggressive progression and irreversible joint damage. Hence, early identification of disease-specific processes of joint inflammation and erosion - at the onset of disease or later - is of key importance for the patient's prognosis and therapeutic strategy. This can be achieved today with great precision and reliability through the use of modern imaging methods like arthrosonography and magnetic resonance imaging (MRI). The REMISSION(PLUS) initiative aspire to integrate modern imaging technologies as standard methods in the care and management of RA patients. The main areas on which this initiative will be focusing are the conceptualization and implementation of educational programs and training seminars on sonography and MRI, the development and establishment of case report forms for standardized documentation of findings, and the systematic monitoring of patients on treatment, with the aim of producing very precise documentation of structural change processes in RA and also, if possible, to document radiological remission or even progression. The REMISSION(PLUS) project also includes the setting up of specialized centers of excellence, which will network to support the implementation and access to the various imaging procedures at hospitals, rheumatology clinics and rheumatology practices nationwide.
17279204 Care pathways in early rheumatoid arthritis. 2006 Nov OBJECTIVE: To determine the proportion of family physicians who diagnose rheumatoid arthritis (RA) correctly and to note how they report they would manage RA patients. DESIGN: Mailed survey (self-administered questionnaire) requesting comments on vignettes. SETTING: Province of Quebec. PARTICIPANTS: Computer-generated random sample of family physicians registered with the Quebec College of Family Physicians. MAIN OUTCOME MEASURES: The proportion of family physicians who recognized RA and their reported management strategies. RESULTS: Most respondents recognized the vignette presentation as a case of RA; 133/138 (96.4%) indicated RA as their provisional diagnosis, and all but 1 of the remaining respondents listed RA as a differential diagnosis. Of those who considered RA as a provisional or possible diagnosis, 107 (77.5% of all respondents) suggested referring the patient to a rheumatologist. Among the physicians who suggested referral, none indicated they would initiate disease-modifying antirheumatic drugs (DMARDs). CONCLUSION: Almost all respondents considered RA as a provisional or differential diagnosis. Although many suggested referring the patient to a rheumatologist, almost a quarter did not. Initiating DMARDs before referring patients to rheumatologists appears to be rare. Since DMARDs given during the early stages of RA are known to decrease damage and dysfunction, ways to increase their use and optimize care pathways for new-onset inflammatory arthritis are urgently needed.
16920570 Treatment of rheumatoid arthritis with rituximab: an update and possible indications. 2006 Aug Based on new biologic and clinical insights, the number of drugs blocking different biologic targets in rheumatoid arthritis (RA) [e.g., tumor necrosis factor alpha (TNFalpha), CTLA4, interleukin (IL)-1, IL-6, IL-15, IL-18, B lymphocyte stimulator (BLyS), CD20] has increased considerably over the last decade. Rituximab, a chimeric monoclonal antibody that was developed for the treatment of B-cell lymphomas, has been used in different autoimmune diseases where B-cells are thought to play a pivotal role. However, blinded randomised controlled trials have been completed only for RA so far, indicating the clear efficacy of B-cell blockade in RA and highlighting the pathogenetic B-cell in rheumatoid synovitis. The use of rituximab in RA is herein updated, from early preliminary studies to more recent presentations in International Conferences. Key clinical and biologic issues are discussed, i.e., efficacy and safety of rituximab, role of concomitant therapies, use in the long term and retreatment strategies, differences with anti-TNFalpha therapy. The possible indications in RA are finally discussed, also on the ground of personal experience with rituximab in RA and other rheumatic diseases associated with B-cell lymphoproliferation. Further clinical research should go hand in hand with laboratory research, and tissue studies are now needed.