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ID PMID Title PublicationDate abstract
17186727 [Comparative analysis via data mining on the clinical features of Western medicine and Chi 2006 Nov OBJECTIVE: To compare the clinical characteristics of traditional Chinese medicine (TCM) and Western medicine (WM) in diagnosing rheumatoid arthritis (RA). METHODS: A total of 85 clinical RA related messages were enacted and classified into 5 sets as pathological locations, quantitative diagnosis, symptomatic descriptions, general status and environment factors. The respective frequency of their presence in the TCM or WM data sets for RA diagnosis collected from MEDLINE and China National Knowledge Infrastructure (CNKI) were analyzed statistically by Chi-square test, and the relationship of some TCM diagnostic factors/conditions with the RA related biological factors was analyzed by co-occurrence-based literature approach of mining. RESULTS: There was significant difference between the diagnostic pattern of WM and TCM (P < 0.01). Compared with that of WM, TCM diagnosis on RA paid more attention to environmental factors and symptomatic descriptions, which showed definite association with the cytokines and neuro-endocrine factors in RA. CONCLUSION: Examination of environmental factors and symptomatic descriptions for RA diagnosis is one of the important characteristics of TCM treatment in accordance to syndrome differentiation, it has its potential biologic basis. A novel approach is proposed for exploring the characteristics of TCM in diagnosis and observation.
17075598 Strategies to control disease in rheumatoid arthritis with tumor necrosis factor antagonis 2006 Nov Recent data have shown that disability and joint destruction in rheumatoid arthritis (RA) occur early on in the course of the disease and progress rapidly. It has been shown that in the early stages of RA, disability is attributed to increased disease activity, whereas later in the course of the disease, disability results from irreversible joint damage. These findings support the need to develop treatment strategies that will rapidly bring the disease under control, with the ultimate goal of alleviating symptoms and halting progressive joint damage. A number of such strategies have been evaluated, including the early administration of a biologic agent alone or in combination with high-dose methotrexate. Other, more recent treatment strategies include the tight control of disease activity by targeting specific outcomes necessary for decision making; the use of biologic agents for the treatment of moderate disease; and the induction of remission with a biologic agent early in the course of disease, followed by maintenance therapy using a conventional disease-modifying antirheumatic drug. The substantial positive effect these strategies have on patient outcomes supports the concept that the optimal management of RA involves aggressive early therapy combined with close monitoring of disease progression and modification of ineffective therapeutic strategies.
16438798 ROS as signalling molecules in T cells--evidence for abnormal redox signalling in the auto 2005 Reactive oxygen species are recognised as important signalling molecules within cells of the immune system. This is, at least in part, due to the reversible activation of kinases, phosphatases and transcription factors by modification of critical thiol residues. However, in the chronic inflammatory disease rheumatoid arthritis, cells of the immune system are exposed to increased levels of oxidative stress and the T cell becomes refractory to growth and death stimuli. This contributes to the perpetuation of the immune response. As many of the effective therapies used in the treatment of rheumatoid arthritis modulate intracellular redox state, this raises the question of whether increased oxidative stress is causative of T-cell hyporesponsiveness. To address this hypothesis, this review considers the putative sources of ROS involved in normal intracellular signalling in T cells and the evidence in support of abnormal ROS fluxes contributing to T-cell hyporesponsiveness.
15742154 The inhibitory co-receptor, PECAM-1 provides a protective effect in suppression of collage 2005 Jan Studies of PECAM-1(-/-) mice have identified that PECAM-1 functions as an inhibitory co-receptor to modulate immunological responsiveness. In this study, we describe the in vivo consequences of PECAM-1 deficiency in mouse models of collagen-induced arthritis (CIA) and K/BxN passive transfer model that resembles many of the features of human rheumatoid arthritis. Immunization of PECAM-1(-/-) C57BL/6 (H-2b) mice with chicken collagen type II induced CIA with an incidence of 82% by day 49, while 33%; of wild-type and 100% of DBA/1 mice developed arthritis in a similar time frame. The mean onset of disease for PECAM-1(-/-) C57BL/6 mice was day 32 compared to day 51 for wild-type C57BL/6 mice and day 18 for DBA/1 mice (H-2q susceptible). In terms of disease severity, the mean maximal arthritic index for PECAM-1(-/-) C57BL/6 mice was comparable to DBA/1 mice (8.91 +/- 0.91 vs 11.67 +/- 0.82). This mean maximal index in PECAM-1(-/-) C57BL/6 mice was significantly higher than wild-type C57BL/6 mice (5.00 +/- 0.73). IgG1 and IgG2b antibody responses against CII were elevated in arthritic PECAM-1(-/-) C57BL/6 mice compared to wild-type C57BL/6 mice. Histological examination of arthritic paws of PECAM-1(-/-) C57BL/6 mice revealed inflammatory infiltrates of lymphocytic/monocytic cells and cartilage/bone destruction similar to CIA-induced DBA/1 arthritic paws. In the K/BxN model, the arthritis was not augmented in PECAM-1(-/-) mice compared to wild-type mice. In contrast, in active CIA, PECAM-1(-/-) mice developed severe disease comparable to susceptible DBA/1 mice and profoundly more severe than C57BL/6 mice, where only one third developed a mild/moderate disease. Together these observations suggest that PECAM-1 plays a crucial role in the suppression of development of autoimmune arthritis.
17076589 Gender-specific pharmacology: implications for therapy. 2006 Aug Historically, research into drugs and diseases has assumed that beyond the reproductive system, gender differences did not exist or were not relevant. Interest in recognizing the importance of gender-based differences in pharmacology and disease has been fueled in recent years by an increasing amount of data revealing variations in drug efficacy and side effect profiles between the genders as well as differences in disease prevalence.
15895883 Distinctive effects of G-CSF, GM-CSF and TNFalpha on neutrophil apoptosis in systemic lupu 2005 Mar OBJECTIVE: To investigate the influence of culture with G-CSF GM-CSF and TNFalpha on neutrophil apoptosis, comparing neutrophils from SLE patients with rheumatoid arthritis (RA) patients and healthy control subjects. METHODS: Neutrophils were isolated from SLE (n= 10), RA (n= 10) and healthy control subjects (n= 10), and cultured with two different concentrations of G-CSF, GM-CSF and TNFalpha. Proportion of apoptotic neutrophils at T=0, T=2hrs and T=24hrs was measured using FITC-labelled annexinV and flow cytometry. RESULTS: Significantly more neutrophils were apoptotic at T=0 in the SLE subjects than in the other groups (median, range--Control 3.5% (0.3-7.9) SLE 9.5% (2.9-29.1) RA 3.0% (0.4-23.0) p<0.05). Following culture for 24 hours with 1ng/ml G-CSF the proportion of apoptotic neutrophils from SLE subjects was significantly increased (median, range = 51.6% (27.0-84.0) without G-CSF v 66.8% (31.8-89.2) with G-CSF p<0.05). This was not observed with RA or control subjects, in whom the trend was towards inhibition of apoptosis. Similar trends were seen with GM-CSF There was significant induction of apoptosis in SLE neutrophils after 2 hr culture with 1ng/ml TNFalpha (median, range = 2.3% (0.1-8.0) without TNFalpha v 5.2% (1.0-22.4) with TNFalpha). No significant change was seen in the other groups. There was an inverse correlation between total neutrophil count and the degree of induction of apoptosis by G-CSF and GM-CSF, determined at a range of time-points and cytokine concentrations CONCLUSIONS: Neutrophils from SLE patients display resistance to the apoptosis-inhibiting effects of G-CSF and possibly GM-CSF, and appear more susceptible to the apoptosis-inducing action of TNFalpha, the greatest resistance being observed in the more neutropenic patients.
16356189 Analysis of Fcgamma receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major su 2006 The Fcgamma receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A-FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13-8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44-17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A-FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis.
16222409 MRI appearance of retrocalcaneal bursitis and rheumatoid nodule in a patient with rheumato 2006 Sep Rheumatoid arthritis is an autoimmune disorder of unknown etiology characterized by symmetric, erosive synovitis and sometimes multisystem involvement. Rheumatoid nodules have been reported in as many as 20-30% of patients with rheumatoid arthritis; however, they are not commonly seen in the feet. We present magnetic resonance (MR) findings of a rarely seen case of rheumatoid bursitis in the retrocalcaneal bursa associated with a subcutaneous rheumatoid nodule inferior to the calcaneus which histologically confirmed the rheumatoid arthritis. To the best of our knowledge, this is the first case that rheumatoid bursitis in the retrocalcaneal bursa associated with the rheumatoid nodule in the foot was revealed by MR imaging.
16447241 Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associat 2006 Feb OBJECTIVE: Pneumonia is a major cause of mortality and morbidity in rheumatoid arthritis (RA). This study was undertaken to determine the rate and predictors of hospitalization for pneumonia and the extent to which specific RA treatments increase pneumonia risk. METHODS: RA patients (n = 16,788) were assessed semiannually for 3.5 years. Pneumonia was confirmed by medical records or detailed patient interview. Covariates included RA severity measures, diabetes, pulmonary disease, and myocardial infarction. Cox proportional hazards regression was used to determine the multivariable risk associated with RA treatments. RESULTS: After adjustment for covariates, prednisone use increased the risk of pneumonia hospitalization (hazard ratio [HR] 1.7 [95% confidence interval 1.5-2.0]), including a dose-related increase in risk (< or = 5 mg/day HR 1.4 [95% confidence interval 1.1-1.6], > 5-10 mg/day HR 2.1 [95% confidence interval 1.7-2.7], > 10 mg/day HR 2.3 [95% confidence interval 1.6-3.2]). Leflunomide also increased the risk (HR 1.2 [95% confidence interval 1.0-1.5]). HRs for etanercept (0.8 [95% confidence interval 0.6-110]) and sulfasalazine (0.7 [95% confidence interval 0.5-1.0]) did not reflect an increased risk of pneumonia. HRs for infliximab, adalimumab, and methotrexate were not significantly different from zero. CONCLUSION: There is a dose-related relationship between prednisone use and pneumonia risk in RA. No increase in risk was found for anti-tumor necrosis factor therapy or methotrexate. These data call into question the belief that low-dose prednisone is safe. Because corticosteroid use is common in RA, the results of this study suggest that prednisone exposure may have important public health consequences.
17184535 The impact of rheumatoid arthritis on foot function in the early stages of disease: a clin 2006 Dec 21 BACKGROUND: Foot involvement occurs early in rheumatoid arthritis but the extent to which this impacts on the structure and function leading to impairment and foot related disability is unknown. The purpose of this study was to compare clinical disease activity, impairment, disability, and foot function in normal and early rheumatoid arthritis (RA) feet using standardised clinical measures and 3D gait analysis. METHODS: Twelve RA patients with disease duration < or =2 years and 12 able-bodied adults matched for age and sex underwent 3D gait analysis to measure foot function. Disease impact was measured using the Leeds Foot impact Scale (LFIS) along with standard clinical measures of disease activity, pain and foot deformity. For this small sample, the mean differences between the groups and associated confidence intervals were calculated using the t distribution RESULTS: Moderate-to-high foot impairment and related disability were detected amongst the RA patients. In comparison with age- and sex-matched controls, the patients with early RA walked slower (1.05 m/s Vs 1.30 m/s) and had a longer double-support phase (19.3% Vs 15.8%). In terminal stance, the heel rise angle was reduced in the patients in comparison with normal (-78.9 degrees Vs -85.7 degrees). Medial arch height was lower and peak eversion in stance greater in the RA patients. The peak ankle plantarflexion power profile was lower in the patients in comparison with the controls (3.4 W/kg Vs 4.6 W/kg). Pressure analysis indicated that the RA patients had a reduced lesser toe contact area (7.6 cm2 Vs 8.1 cm2), elevated peak forefoot pressure (672 kPa Vs 553 kPa) and a larger mid-foot contact area (24.6 cm2 Vs 19.4 cm2). CONCLUSION: Analysis detected small but clinically important changes in foot function in a small cohort of RA patients with disease duration <2 years. These were accompanied by active joint disease and impairment and disability.
16868535 New radiopharmaceuticals for imaging rheumatoid arthritis. 2006 Sep Rheumatoid arthritis (RA) is an incapacitating chronic inflammatory disease of the joints that, because of frequent relapses, requires life-long treatment. In patients affected with RA an important treatment objective is to achieve specific immune suppression in order to extinguish the immune process and arrest the disease, thus preventing or delaying complications and avoiding disease recurrence. The side effects of anti-inflammatory drugs given to improve the quality of life of these patients can be reduced with the use of specific immune therapies that block, as selectively as possible, the pathologic mechanism responsible for the disease. New therapeutic options for specific, targeted therapies for treating RA are being developed, and trials to assess the efficacy and safety of these approaches are underway. However, these therapies rely primarily on clinical assessment to evaluate treatment efficacy. It would be useful, therefore, to have an objective and reliable method that directly highlights the immune processes underlying the disease. Currently available radiopharmaceuticals for imaging RA, with a special emphasis on recently developed agents and their use in therapy decision-making and follow-up are the focus of this article.
16802346 Overexpression of synoviolin in peripheral blood and synoviocytes from rheumatoid arthriti 2006 Jul OBJECTIVE: Synoviolin is a novel E3 ubiquitin ligase that has been implicated in the pathogenesis of rheumatoid arthritis (RA). The purpose of this study was to examine the expression and regulation of synoviolin by tumor necrosis factor alpha (TNFalpha), both in vivo and in vitro. METHODS: A total of 54 RA patients and 23 healthy control subjects were analyzed before, 4 hours after the first infusion, and at week 22 of infliximab treatment. Clinical response was assessed by the American College of Rheumatology criteria for 20% improvement and the Disease Activity Score in 28 joints (DAS28) at 6 months. Synoviolin messenger RNA expression was measured by real-time reverse transcription-polymerase chain reaction in peripheral blood (PB) and fibroblast-like synoviocytes (FLS) and with and without TNFalpha or interleukin-1beta (IL-1beta) stimulation. RESULTS: Synoviolin expression was increased in whole PB obtained from RA patients as compared with that from healthy controls and was significantly reduced early and late after infliximab treatment in responders, but in not nonresponders. Reduction in synoviolin expression was associated with reduced levels of markers of disease activity, including C-reactive protein levels. Nonresponders to infliximab therapy had significantly higher synoviolin expression at baseline as compared with responders, and this elevation persisted despite infliximab therapy. PB CD14+ monocytes expressed increased synoviolin levels compared with CD3+ lymphocytes, and TNFalpha or IL-1beta induced a further increase in expression in CD3+ cells. TNFalpha or IL-1beta induced sustained synoviolin expression in RA FLS. CONCLUSION: Elevated PB levels of synoviolin were identified in circulating PB mononuclear cells and were associated with nonresponse to infliximab treatment. Sustained up-regulation of synoviolin by IL-lbeta and TNFalpha may contribute to prolonged survival of immune cells and dysregulated FLS proliferation, leading to RA chronicity.
16449363 Fatigue in rheumatoid arthritis reflects pain, not disease activity. 2006 Jul OBJECTIVE: We determined the amount of fatigue experienced by patients with RA, and its relationship to synovitis, pain and other common clinical features. We also examined to what extent RA fatigue is improved by disease-modifying antirheumatic drugs (DMARDs) and anti-tumour necrosis factor (TNF) therapy. METHODS: We studied two cohorts of 238 and 274 RA patients cross-sectionally and examined treatment responses in 30 RA patients starting anti-TNF and 54 starting DMARDs followed for 3 and 6 months. We measured fatigue using visual analogue scores (VAS) and Medical Outcomes Study Short Form 36 (SF-36) vitality scores. We recorded the disease activity score for 28 joints and its components (tender/swollen joint counts, patient global assessment, ESR), morning stiffness, health assessment questionnaire, physician global assessment, erosive disease, nodules, rheumatoid factor, concomitant medications and illnesses, and the SF-36 questionnaire. RESULTS: Fatigue was common in RA patients; over 80% had clinically relevant fatigue (VAS > or =20 mm), over 50% had high levels (VAS > or =50 mm). It was associated with pain and changes in mental health, particularly depression. In each of the two cross-sectional cohorts, this relationship was similar whichever measures of fatigue and mental health were used. Fatigue fell with DMARDs and anti-TNF: before treatment, 87% of patients had high fatigue, after treatment this fell to 50%. These treatment effects were mainly linked to improvements in pain. CONCLUSIONS: High fatigue levels characterize RA and are mainly linked to pain and depression. The association with disease activity is secondary. Fatigue falls with DMARD and anti-TNF therapy. The balance of evidence suggests that fatigue is centrally mediated in established RA.
16055108 Assessment of paraoxonase 1 activity and malondialdehyde levels in patients with rheumatoi 2005 Oct OBJECTIVES: We aimed to evaluate antioxidant paraoxonase 1 activity together with malondialdehyde (MDA) (an oxidative stress parameter) levels in patients with rheumatoid arthritis. DESIGN AND METHODS: Fifty-seven rheumatoid arthritis patients were included in the study and subgrouped according to disease activity (active, n = 31; inactive, n = 26) and compared with healthy controls (n = 25). Serum paraoxonase 1 activity and MDA levels were measured according to an enzymatic spectrophotometric method. RESULTS: Serum MDA level was higher (P = 0.001) whereas paraoxonase 1 activity was lower (P = 0.001) in the patient group than the controls. When active and inactive subgroups were compared with the control group, there was a statistically significant difference between each parameter. Serum MDA levels were significantly higher, while paraoxonase 1 activity was lower in the active and inactive rheumatoid arthritis groups than the control group. But there was not any difference between active and inactive patients with RA. There was a negative correlation between MDA levels and paraoxonase 1 activity. CONCLUSIONS: Increased reactive oxygen species levels in rheumatoid arthritis may result in a pro-oxidation environment, which in turn could result in decreased antioxidant paraoxonase 1 activity and increased MDA levels.
16205925 Classic disease modifying anti-rheumatic drugs (DMARDs) in combination with infliximab. Th 2006 Jun To assess the performance of infliximab in a clinical setting, 364 rheumatoid arthritis (RA) patients from the National Register of Biological Treatment in Finland (ROB-FIN) were analysed. Corticosteroid usage and dose diminished (p<0.05 and 0.001, respectively) in patients on infliximab, of whom 51% also used one, 28% two and 16% three other concomitant DMARDs. A 34% of the RA patients used methotrexate+/-corticosteroids without any other DMARD. Methotrexate was most frequently used with sulphasalazine and/or hydroxychloroquine. Non-methotrexate patients most frequently used leflunomide or azathioprine combined with corticosteroids. The clinical effect of these combinations was similar to that of infliximab with methotrexate alone. The results indicate that infliximab can be used together with other DMARDs than methotrexate alone, quite according to the philosophy of the combination drug therapy, as the effectiveness is as good as or even slightly better than that of methotrexate and infliximab.
16539813 Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumat 2006 Jan OBJECTIVE: The findings of the involvement of tissue transglutaminase (tTg) in the pathogenesis of coeliac disease (CD) have stimulated progress in the field of auto-immune diseases. Another calcium-dependent cysteine enzyme, peptidylarginine deiminase type 4 (PAD4), seems to be involved in the pathogenesis of rheumatoid arthritis (RA). There are obvious similarities between Tgs and PADs. METHODS: Using enzyme-linked immuno-sorbent assays, we have measured the occurrence of antibodies against guinea pig (gp) and human recombinant (hr) tTg, PAD and citrulline in 59 controls and 184 RA-patients, of whom 71 were treated with methotrexate (mtx). RESULTS: In addition to the expected antibodies against citrulline (62%), sera from the 113 RA-patients without mtx treatment contained significantly increased frequencies of IgG anti-PAD (35%), IgA anti-gp-tTg (34%), IgA anti-hr tTg (20%), IgG anti-gp-tTg (13%) and IgA anti-hr-FXIII (15%) compared to controls. In sera from the mtx-treated RA-patients the expression of antibodies was reduced. In patients not treated with methotrexate there was a statistically significant correlation between, on one hand, IgG anti-PAD and on the other hand, IgG anti-citrulline, IgA anti-gp-tTg, IgA anti-hr-tTg, IgG anti-gp-tTg, IgG anti-hr-tTg, or IgA anti-hr-FXIII. In the mtx-treated group these correlations were less pronounced. CONCLUSION: In addition to the expected antibodies against citrulline, sera from RA-patients contained antibodies against PAD and against Tgs of at least two kinds, indicating that the specificity for anti-tTg in CD is far from complete. Most of the patients displayed more than one antibody, a possible indication of epitope spreading. MTX-treatment reduced the expression of antibodies.
17039307 Autoimmunity to citrullinated type II collagen in rheumatoid arthritis. 2006 The production of autoantibodies to citrullinated type II collagen and the citrullination of type II collagen were analyzed in rheumatoid arthritis. Autoantibodies to citrullinated type II collagen were detected in 78.5% of serum samples from 130 rheumatoid arthritis patients. Autoantibodies to native noncitrullinated type II collagen were detected in 14.6% of serum samples, all of which were positive for anti-citrullinated type II collagen antibodies. Serum samples were also positive for anti-citrullinated type II collagen antibodies in 1 of 31 systemic lupus erythematosus patients and 2 of 55 patients with osteoarthritis of the knee. In contrast, sera samples from 24 systemic sclerosis patients, 21 dermatomyositis/polymyositis patients, 21 ankylosing spondylitis patients, and 18 psoriatic arthritis patients were all negative for anti-citrullinated type II collagen antibodies. Anti-citrullinated type II collagen antibodies and fragments of citrullinated type II collagen were found in the synovial fluid obtained from affected knee joints of 15 rheumatoid arthritis patients. Moreover, anti-citrullinated type II collagen antibodies were isolated from the synovium of affected knee joints in 8 rheumatoid arthritis patients using antigen/antibody immunocomplex dissociation buffer but not by using standard buffers. These findings indicate that autoantibodies that react with citrullinated type II collagen are specifically produced and that immunocomplexes composed of fragments of citrullinated type II collagen and autoantibodies are deposited in the inflamed articular synovium in rheumatoid arthritis patients. Assaying for the presence of anti-citrullinated type II collagen antibodies may therefore be useful for diagnosing rheumatoid arthritis, and the deposition of these immunocomplexes in the articular synovium may be involved in pathogenesis.
16620141 B cell-targeted therapy for rheumatoid arthritis: an update on the evidence. 2006 Rheumatoid arthritis (RA) is a human systemic autoimmune disease with a prevalence of about 1%. Although an important role for B cells has been demonstrated in animal models of autoimmune, inflammatory arthritis, the importance of B cells in RA has been controversial for decades. The development of therapies targeting B cells may help to resolve this debate. Rituximab, a mouse-human chimeric monoclonal antibody against the B cell-specific antigen CD20, was the first B cell-targeted therapy tested in double-blind, placebo-controlled trials for RA. On the basis of the data from three separate trials, addition of rituximab to methotrexate appears to reduce significantly the signs and symptoms of rheumatoid factor-seropositive RA, as assessed by American College of Rheumatology (ACR) 20, 50 and 70 response criteria, and to be relatively safe. Significant questions about rituximab therapy still need to be addressed, including whether or not treatment with rituximab reduces radiographic progression of joint damage, the safety and efficacy of repeated courses of rituximab, and the long-term effects of rituximab on the immune system. Preliminary data on treatment of RA with belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (a growth and survival factor for B cells) is now available. In a double-blind, placebo-controlled, phase II trial, belimumab was well tolerated and had a significant beneficial effect on the ACR 20 response. Thus, therapies specifically targeting B cells do appear to be effective in the treatment of RA, providing direct evidence that B cells are important in the pathogenesis of RA.
16507172 Methotrexate in rheumatoid arthritis is frequently effective, even if re-employed after a 2006 Effectiveness of therapy with individual disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is limited, and the number of available DMARDs is finite. Therefore, at some stage during the lengthy course of RA, institution of traditional DMARDs that have previously been applied may have to be reconsidered. In the present study we investigated the effectiveness of re-employed methotrexate in patients with a history of previous methotrexate failure (original course). A total of 1,490 RA patients (80% female, 59% rheumatoid factor positive) were followed from their first presentation, yielding a total of 6,470 patient-years of observation. We identified patients in whom methotrexate was re-employed after at least one intermittent course of a different DMARD. We compared reasons for discontinuation, improvement in acute phase reactants, and cumulative retention rates of methotrexate therapy between the original course of methotrexate and its re-employment. Similar analyses were peformed for other DMARDs. Methotrexate was re-employed in 86 patients. Compared with the original courses, re-employment was associated with a reduced risk for treatment termination because of ineffectiveness (P = 0.02, by McNemar test), especially if the maximum methotrexate dose of the original course had been low (<12.5 mg/week; P = 0.02, by logistic regression). In a Cox regression model, re-employed MTX was associated with a significantly reduced hazard of treatment termination compared with the original course of methotrexate, adjusting for dose and year of employment (hazard ratio 0.64, 95% confidence interval 0.42-0.97; P = 0.04). These findings were not recapitulated in analyses of re-employment of other DMARDs. Re-employment of MTX despite prior inefficacy, but not re-employment of other DMARDs, is an effective therapeutic option, especially in those patients in whom the methotrexate dose of the original course was low.
17175654 The personal impact of rheumatoid arthritis on patients' identity: a qualitative study. 2006 Jun OBJECTIVE: To provide a detailed understanding of the direct personal experiences of living with rheumatoid arthritis (RA) and the impact of the illness upon patients' lives, to inform the improvement of clinical care and training. METHOD: A qualitative study was performed using data from semi-structured interviews with 26 patients who live with RA, recruited at two outpatient clinics in south-east England. RESULTS: In addition to the physical impact of RA on patients' lives, their accounts gave detailed descriptions of how their identity was affected in relation to: (1) their private lives (e.g., difficulties in their relationships, or caring for others); (2) their public roles and responsibilities (e.g., in their paid work and in experiences of stigmatization or discrimination); and (3) their private and public domains (e.g., perceived change of physical appearance, alteration of self-image, and change or loss of social roles). Young patients (25-45 years) did report some differences in their chronic illness experiences, but patients from black and ethnic minorities did not. DISCUSSION: The study highlights new findings which can facilitate more open communication between staff and patients on the personal impact of RA, on patients' coping strategies, and on the effects on their identity both in private and in public. This will allow multidisciplinary outpatient services to provide care more closely matched to the difficulties that are directly experienced by patients.