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ID PMID Title PublicationDate abstract
18848912 Tyrosine kinases as targets in rheumatoid arthritis. 2009 Jan Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation and proliferation of inflammatory cells in the synovial (joint) lining, resulting in the formation of pannus tissue, which invades and destroys adjacent cartilage and bone. In RA macrophages, B cells, mast cells, fibroblast-like synoviocytes (FLSs) and CD4+ T lymphocytes become activated and contribute to synovial inflammation and joint destruction. It has been showed that different tyrosine kinases participate in the activation of those cells having important participation in the physiopathology of RA. Therefore, the tyrosine kinases inhibitors could be the next step in the treatment of patients with RA. This review focuses on recent advances on the role of tyrosine kinases and their inhibitors in the physiopathology of RA.
18957487 Progression of radiographic joint damage in rheumatoid arthritis: independence of erosions 2009 Oct OBJECTIVE: To compare the progression of erosions and joint space narrowing (JSN) in patients with early active rheumatoid arthritis (RA) using data obtained in the "Active-controlled Study of Patients receiving Infliximab for the treatment of Rheumatoid arthritis of Early onset" (ASPIRE) study. METHODS: This was a post hoc analysis of patients in ASPIRE who received placebo plus methotrexate (MTX) or infliximab (3 or 6 mg/kg) plus MTX. Radiographs of the hands (870 patients) and feet (871 patients) were obtained at baseline and week 54 and scored using the van der Heijde/Sharp method. In total, 7160 joints in the placebo plus MTX group and 18,908 joints in the combined infliximab plus MTX group were included in this analysis. RESULTS: At baseline, 83.4% of joints in the placebo plus MTX group had no radiographic damage, 8.5% had only erosions, 4.4% had only JSN and 3.7% had both. The distribution was similar in the infliximab plus MTX group. In the placebo plus MTX group, the majority of joints did not have development or progression of radiographic damage from baseline to week 54; among joints that did have development or progression of damage at week 54, erosions occurred more often than JSN. The same pattern was observed in the infliximab plus MTX group, although the proportions of joints with damage at week 54 were generally larger in the placebo plus MTX group. There was a tendency for joints with existing erosions or JSN to have progression of damage, rather than development of new damage. CONCLUSIONS: Erosions were the predominant type of damage observed in both treatment groups. Erosions and JSN are related but partly independent processes.
19707765 A systematic review and meta-analysis of the efficacy and safety of adalimumab for treatin 2010 Jun Adalimumab (ADA) is a monoclonal antibody. Published studies indicate that its use in patients with rheumatoid arthritis can be efficient in providing long-term benefits. The aim of this study is to evaluate the efficacy and safety of ADA for treating rheumatoid arthritis. A systematic review was performed to search for randomized clinical trials that compare subcutaneous doses of ADA 20 mg weekly or 40 mg every other week with placebo, with or without concomitant methotrexate. Only studies of moderate or high quality were included. A meta-analysis was conducted to assess the efficacy (based in changes of American College of Rheumatology ACR criteria) and the safety (based in serious adverse events, serious infections, malignancy and deaths) of ADA use. Withdrawals due to adverse events or lack of efficacy were also evaluated. Eight studies met the inclusion criteria, comprising 2,692 patients. In the efficacy meta-analysis, a greater number of ADA-treated patients relative to those in placebo group achieved ACR20, ACR50 and ACR70 values from 6 months to 2 years of treatment. For safety results, there were no statistically significant differences between the groups. Withdrawals due to adverse events were higher in ADA group relative to the placebo group, and withdrawals due to the lack of efficacy were higher in placebo group relative to the ADA-treated group. This meta-analysis shows a higher efficacy of ADA relative to placebo, but clinicians should be careful regarding adverse events in ADA-treated patients.
19644846 Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-fr 2009 Aug OBJECTIVE: Remission has become an attainable goal of rheumatoid arthritis (RA) treatment, especially since the advent of biologic antirheumatic therapy. Because little is known about patients who achieve disease remission with conventional treatment, we used 2 large independent inception cohorts to study the prevalence of and predictive factors for disease-modifying antirheumatic drug (DMARD)-free sustained remission after treatment with conventional therapy. METHODS: Remission of disease was assessed in 454 patients from the Leiden Early Arthritis Clinic (EAC) and in 895 patients from the British Early Rheumatoid Arthritis Study (ERAS) who fulfilled the American College of Rheumatology 1987 revised criteria for the classification of RA and were treated with conventional therapy. Sustained DMARD-free remission was defined as fulfilling the following criteria for at least 1 year: 1) no current DMARD use, 2) no swollen joints, and 3) classification as DMARD-free remission by the patient's rheumatologist. Predictive factors were identified by Cox regression analysis. RESULTS: Sustained DMARD-free remission was achieved by 68 of 454 patients (15.0%) in the Leiden EAC and by 84 of 895 patients (9.4%) in the ERAS. Six factors were associated with sustained DMARD-free remission in both cohorts: acute onset, short symptom duration before inclusion, not smoking, little radiographic damage at baseline, absence of IgM rheumatoid factor (IgM-RF), and absence of HLA shared epitope alleles. In the ERAS, low disease activity at baseline was also predictive of remission. Multivariate analyses revealed symptom duration and the absence of autoantibodies (anti-cyclic citrullinated peptide 2 and IgM-RF) as independent predictors. CONCLUSION: Sustained DMARD-free remission in RA patients treated with conventional therapy is not uncommon. Symptom duration at presentation and the absence of autoantibodies are associated with sustained DMARD-free remission.
20047979 Superiority of SDAI over DAS-28 in assessment of remission in rheumatoid arthritis patient 2010 Apr OBJECTIVE: To investigate the accuracy of composite scores in classifying RA patients who are in remission using the absence of inflammatory activity detected by ultrasound (US) as a gold standard. METHODS: Ninety-seven RA patients who were classified by their rheumatologists as being in remission were studied. Disease activity was assessed by the DAS-28 and simplified disease activity index (SDAI). US examination was performed in mode B and power Doppler (PD) in 42 joints. RESULTS: Synovial hypertrophy (SH) and PD were present in 92 (94.8%) and 41 (42.3%) patients. If we consider 'remission' to be the absence of joints with PD signal, no differences were found by DAS-28 between patients in remission and those not in remission, although differences were present by SDAI. We then calculated the sensitivity (S), specificity (Sp) and positive likelihood ratio (LR) of different SDAI cut-off points to predict absence of PD signal. SDAI < 5 had an S of 65% (95% CI 52, 76), Sp of 55% (95% CI 39, 69) and LR of 1.45 (95% CI 0.98, 2.15), whereas SDAI < 3.3 had an S of 57% (95% CI 44, 69), Sp of 74% (95% CI 58, 85) and LR of 2.24 (95% CI 1.25, 4.01). CONCLUSIONS: Our results suggest that the SDAI classification of remission is closer to the concept of an absence of inflammatory activity, as defined by the absence of positive PD signal by US.
19924718 Haplotype-based analysis: a summary of GAW16 Group 4 analysis. 2009 In this summary article, we describe the contributions included in the haplotype-based analysis group (Group 4) at the Genetic Analysis Workshop 16, which was held in September 17-20, 2008. Our group applied a large number of haplotype-based methods in the context of genome-wide association studies. Two general approaches were applied: a two-stage approach that selected significant single-nucleotide polymorphisms (SNPs) in the first stage and then created haplotypes in the second stage and genome-wide analysis of smaller sets of SNPs selected by sliding windows or estimating haplotype blocks. Genome-wide haplotype analyses performed in these ways were feasible. The presence of the very strong chromosome 6 association in the North American Rheumatoid Arthritis Consortium data was detected by every method, and additional analyses attempted to control for this strong result to allow detection of additional haplotype associations.
20091033 Cardiac complications in rheumatoid arthritis in the absence of occlusive coronary patholo 2012 Feb Cardiovascular disease is the leading cause of premature mortality in patients with rheumatoid arthritis (RA). Pathophysiology of rheumatoid cardiovascular phenomenon is not fully understood, but systemic inflammation is thought to play a crucial role in the endothelial damage and accelerated course of atherosclerotic disease. Rheumatoid inflammation can also cause coronary pathology and heart failure. We present a case of transient cardiomyopathy in RA in the absence of occlusive coronary pathology, which mimics acute coronary syndrome.
20447950 Economic aspects of treatment options in rheumatoid arthritis: a systematic literature rev 2010 Jun OBJECTIVE: To review the cost effectiveness of rheumatoid arthritis (RA) treatments and inform the clinical recommendations by the European League Against Rheumatism. METHODS: A systematic literature search and review of the health economic evidence on RA treatment options was performed. RESULTS: Despite diverse methodological approaches, health economic analyses are concordant: at onset of disease, traditional disease-modifying antirheumatic drugs (DMARDs) are cost effective-that is, treatment merits outweigh treatment costs. If DMARDs fail, therapeutic escalation with tumour necrosis factor alpha inhibitors (TNFi) is cost effective when standard dosing schemes are employed. If TNFi fail, rituximab or abatacept is cost effective. Economic evidence for switching TNFi remains sparse. CONCLUSIONS: The costly sequelae of insufficiently controlled RA justify intensive escalations of treatment in this disease. By maintaining function, patients are kept in the work process, reducing indirect costs. Quality of life is improved at an expense commonly accepted for chronic diseases. Effective control of disease activity seems to be a prudent use of societal resources.
19165557 Focal myocarditis mimicking myocardial infarction in a patient with rheumatoid arthritis. 2009 Apr Cardiovascular features in rheumatoid arthritis (RA) are common. However, RA associated with acute myocarditis is seldom described. Here, we report the case of a 58-year-old woman with rheumatoid arthritis and end stage renal disease who suffered chest tightness and diaphoresis during hemodialysis. The electrocardiogram showed ST elevations and the echocardiographic study revealed abnormalities of regional wall motion with moderate left ventricle dysfunction. Acute ST-elevation myocardial infarction was impressed according to clinical presentations and elevated cardiac enzymes. However, emergent coronary angiography revealed no significant coronary stenosis. Magnetic resonance imaging ultimately made the diagnosis of myocarditis. The patient improved gradually without immunosuppressive therapy. This case shows that conservative treatment is a feasible strategy for acute myocarditis in a patient with rheumatoid arthritis.
20147446 Apoptosis in the rheumatoid arthritis synovial membrane: modulation by disease-modifying a 2010 May OBJECTIVES: RA is characterized at the synovial tissue level by synovial lining hyperplasia, angiogenesis and mononuclear cell infiltrates. A failure of apoptotic pathways may explain these pathological changes in RA synovial tissue. This study aims to demonstrate the presence of initiators and inhibitors of apoptosis in RA synovial tissue and the effect of treatment with DMARDs on apoptotic pathways in RA. METHODS: Synovial biopsy specimens were obtained at arthroscopy from 16 RA patients before and at 3- or 6-month intervals after commencing treatment with a DMARD. Apoptosis (by the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling method and polyADP-ribose polymerase staining), proteins regulating apoptosis [Fas, FADD-like IL1b converting enzyme inhibitory protein (FLIP), Bcl-2, Survivin and X-linked inhibitor of apoptosis protein (XIAP)] and the presence of activated caspases (caspases 3 and 8) were detected by immunohistochemistry and quantified using image analysis and semiquantitative techniques. RESULTS: Fifteen patients responded to treatment, with an ACR response of > or =20%, 13 achieving an ACR response of > or =50% and 3 achieving an ACR remission. There was a significant reduction in SM macrophages and memory T cells, with an increase in fibroblast-like synovial lining cells following DMARD treatment. Apoptosis was not detected in the inflamed synovial tissue of RA patients before starting treatment, despite evidence of caspase activation, but was detectable after successful treatment with DMARDs. Inhibitors of activated caspases (FLIP, Survivin and XIAP) were detected in RA synovial tissue and were down-modulated with successful DMARD treatment. CONCLUSIONS: Apoptotic pathways are defective in RA synovial tissue from patients with active disease, despite the presence of activated caspases, possibly due to the abundant expression of inhibitors of the caspase pathway in RA synovial tissue. DMARD treatment can modulate apoptosis in the RA SM, which may lead to restoration of the SM architecture towards that of normal synovial tissue.
19004046 Association between interleukin 1 polymorphisms and rheumatoid arthritis susceptibility: a 2009 Jan OBJECTIVE: To determine whether interleukin 1 (IL-1) polymorphisms confer susceptibility to rheumatoid arthritis (RA). METHODS: We conducted metaanalyses on associations between IL-1 polymorphisms and RA susceptibility, using fixed or random effects models. RESULTS: A total of 18 separate comparisons were made using 10 European, 7 Asian, and 1 Latin American population samples. Metaanalysis of the IL-1B+3954 CC genotype revealed an association with RA in all subjects (odds ratio=0.776, 95% confidence interval=0.609-0.988, p=0.040). In Asians, an association between IL-1B+3954 and RA was identified. In contrast, no association was found between the IL-1B+3954 polymorphism and RA susceptibility in European populations. Metaanalyses of the IL-1B-511 and IL-1RN VNTR polymorphisms identified no association between these polymorphisms and RA. CONCLUSION: Our metaanalysis shows that the IL-1B+3954 polymorphism was associated with the development of RA, but only in Asians.
20663799 'It's this whole picture, this well-being': patients' understanding of 'feeling well' with 2010 Sep OBJECTIVES: The aim of this study was to explore the meaning of 'feeling well' for people with rheumatoid arthritis (RA). METHODS: In-depth interviews were conducted with 23 RA patients, purposively sampled for medication type, disease duration, disease activity, age and gender. Data were analysed using Framework, emphasizing participants' personal contexts. RESULTS: Well-being was viewed as a broad concept, with 'feeling well' being the result of an on-going process to actively engage with a changing body, self and life. Four dimensions emerged: 'Living in the body', 'Being in the mind', 'Adapting to illness' and 'Being in the world'. The physical impact of RA underpinned the global perception of well-being and was clearly described as linking to the experience of psychological well-being. Physical and psychological wellness was often affected by the individual's adaptation to RA and personal context (e.g. home environment, broader social attitudes). DISCUSSION: Well-being is a multidimensional concept that is meaningful to RA patients regardless of medication type and disease severity. Patients commonly illustrated a process of actively engaging in cognitive and behavioural adjustments to move towards wellness. Clinical practice and research must take account of the complexity of well-being in long-term conditions, in order to fulfil patients' expectations.
18758893 Masked early symptoms of pneumonia in patients with rheumatoid arthritis during tocilizuma 2009 Although reports of serious infections in clinical trials for rheumatoid arthritis (RA) with tocilizumab, anti-interleukin6 (IL-6) receptor antibody, have been relatively few, there is still some concern about infections. We report here two cases of patients who developed severe pneumonia during tocilizumab treatment for RA. Both patients initially presented with only minimal clinical symptoms and modest elevations in serum C-reactive protein. Tocilizumab might suppress the early inflammatory symptoms of pneumonia.
20842919 [Cardiovascular diseases in rheumatoid arthritis]. 2010 Jul Risk of cardiovascular diseases is significantly higher in patients with rheumatoid arthritis (RA) than in normal population, leading to higher mortality of these patients. An accelerated atherosclerosis has been considered a basis for the increased cardiovascular risk in RA. Besides classical atherosclerosis risk factors, systemic inflammation plays a substantial role. Indirect mechanisms such as insulin resistance and dyslipidemia may play a role, however, inflammation probably causes direct damage to blood vessels. Thus, systemic inflammation has a primary role and other factors accelerate this process. An adequate anti-inflammatory therapy can have a positive effect also on cardiovascular diseases in RA.
21097657 Prevention of autoimmune rheumatic disease: state of the art and future perspectives. 2010 Dec Prevention of disease can in principle be accomplished by identification of environmental and/or lifestyle risk and protective factors followed by public health measures (such as for smoking and lung cancer), or by modification of the individual's reactions to disease-inducing factors (such as in vaccinations against microbes). This review discusses both options based on emerging understanding of aetiologies in inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The major current opportunity for public health-based prevention lies in avoiding smoking. In RA, recent studies have calculated that, in Sweden (a country characterised by a low frequency of smoking), 20% of all RA cases and 33% of all cases of ACPA-positive RA would not have occurred in a smoke-free society. Smoking is also a major risk factor for SLE but no population attribution is yet available. New avenues for individualised and biology-based prevention are provided by the demonstration that several autoimmune rheumatic diseases are preceded by emergence of subclinical autoimmunity followed by laboratory-based signs of inflammation and finally overt disease. Examples of this process are provided from studies of autoimmunity to citrullinated proteins (in RA), to dsDNA (in SLE in general) and to Ro52 epitopes (in the case of neonatal heart block). The recognition of this sequence of events provides opportunities to intervene specifically and potentially curatively before onset of full-blown disease. Such prevention can be accomplished by modification of inciting antigens (environment), by modification of immunity (more or less specific immunomodulation) or by modification of specific gene functions. In all cases, prevention will be different in different subsets of disease and differ at different time points of disease development. Thus, the road map towards prevention of autoimmune rheumatic diseases includes increased understanding of how genes, environment and immunity interact.
20506530 Classification of rheumatologic opinion on early inflammatory arthritis: harmonization of 2010 Oct OBJECTIVE: Interrater variability limits rheumatologic opinion as a reference standard for early inflammatory arthritis (IA) classification. The study objectives were to determine whether rheumatologic opinion is associated with potential early IA classification methods despite high interrater variability, and to compare the relative strengths of those associations. METHODS: Eighteen rheumatologists independently classified 30 initial rheumatology presentation summaries as early IA or not and recommended a pharmacotherapy. Case fulfillment of the following classification methods was independently determined: early referral to rheumatology recommendation for rheumatoid arthritis (ERRR), common early IA cohort inclusion criteria (CEAC), and prevalent IA classification criteria (American College of Rheumatology [ACR]/European Spondylarthropathy Study Group [ESSG]). Associations between rheumatologic opinion, disease-modifying antirheumatic drug (DMARD) recommendation, and each classification method were determined. RESULTS: Participating rheumatologists published on early IA and represented 3 continents. The median case was age 43 (interquartile range [IQR] 30-53) years, had 40 (IQR 24-104) weeks of symptoms, 60 (IQR 18-120) minutes of morning stiffness, a swollen joint count of 6 (IQR 1-13), and an erythrocyte sedimentation rate of 25 (IQR 10-51) mm/hour. The mean ± SD multiple-rater kappa for rheumatologic opinion on early IA was 0.16 ± 0.02. The common odds ratios for associations between rheumatologic opinion and ERRR, CEAC, and ACR/ESSG were 10.3 (95% confidence interval [95% CI] 4.6-23.2), 4.4 (95% CI 2.5-7.7), and 0.7 (95% CI 0.4-1.1), respectively. Odds ratios for associations between DMARD recommendation and ERRR, rheumatologic opinion, CEAC, and ACR/ESSG were 18.7 (95% CI 8.1-43.2), 10.6 (95% CI 6.0-18.8), 2.8 (95% CI 1.7-4.6), and 0.5 (95% CI 0.3-0.7), respectively. CONCLUSION: Classification methods can be used to harmonize rheumatologic opinion of early IA despite high interrater variability. The ERRR is very strongly associated with both rheumatologic opinions of early IA and DMARD treatment recommendations.
19952091 Validity and responsiveness of the World Health Organization Disability Assessment Schedul 2010 Feb OBJECTIVE: To investigate the validity and responsiveness of the World Health Organization Disability Schedule II (WHODAS II) in patients with established RA. METHODS: In 85 RA patients admitted for rehabilitation, the WHODAS II (0-100) was applied at admission and 6 weeks after discharge. Additional assessments included measures of physical and psychological functioning, disease activity and quality of life. The internal consistency of the WHODAS II was determined with Cronbach's-alpha. Associations between the WHODAS II and other outcome measures were determined by Pearson's rank correlation coefficients. Responsiveness measures included the standardized response mean (SRM), effect size (ES) and responsiveness ratio (RR). RESULTS: Cronbach's-alpha of the WHODAS II total score was 0.91. The baseline WHODAS II total score correlated significantly with all other outcome measures, except for the 50-feet walk test, the timed-stands test and the Escola Paulista de Medicina Range of Motion scale. The mean WHODAS II total score improved from 40.5 (s.d. 14.9) at baseline to 4.6 at 6 weeks after discharge (95% CI -8.1, -1.2). The WHODAS II responsiveness scores were -0.35 (SRM), -0.34 (ES) and -0.58 (RR) at 6 weeks after discharge. CONCLUSION; The WHODAS II appeared to be internally consistent, valid and responsive to assess disability in patients with established RA admitted for multidisciplinary team care in terms of International Classification of Functioning, Disability and Health. The WHODAS II showed significant floor effects regarding the subscales--'understanding communicating' and 'getting along with people'. In a multidisciplinary setting, the additional use of measures to evaluate personal and environmental factors seems warranted.
20929971 Health-related quality of life and continuation rate on first-line anti-tumour necrosis fa 2011 Jan OBJECTIVES: To describe changes in health-related quality of life (HRQoL) up to 60 months after commencing anti-TNF therapy for RA patients enrolled in the Australian Rheumatology Association Database (ARAD), and to determine the continuation rate and predictors of discontinuation of first-line anti-TNF therapy. METHODS: Responses to the HAQ, Assessment of Quality of Life, Medical Outcomes Study Short Form-36 (SF-36) and European Quality of Life-5 Dimensions (EQ-5D) were extracted from ARAD for patients commencing anti-TNF therapy and analysed in 6-monthly intervals from the start date. Predictors of discontinuation of therapy were assessed using Cox regression. RESULTS: Since September 2001, 2601 RA patients have enrolled in ARAD; 1801 have used anti-TNF therapy. Before starting the therapy, all HRQoL scores were below the population norms, but showed improvements in the first 6 months. From 12 to 60 months, HRQoL remained stable but below population means. Data to 60 months were available for 106 patients; 47% were still on first-line therapy at 5 years, all were using concurrent DMARDs and 55% were using concurrent prednisolone. Predictors of discontinuation of therapy were poorer HRQoL scores, a more recent therapy start date, concurrent prednisolone use and self-reported severe infection. Older patients and those with longer symptom duration were more likely to remain on therapy. CONCLUSIONS: In routine practice, HRQoL scores improve rapidly within 6 months of starting anti-TNFs and then remain stable for up to 60 months. Almost half remain on first-line therapy.
19526305 Multiple extra-articular synovial cysts complicated with rheumatoid arthritis. 2009 Multiple extra-articular synovial cysts (MESC) are rarely complicated with various rheumatic diseases. We here first report a rheumatoid arthritis (RA) patient with MESC, which were extensively analyzed by a series of imaging techniques including fluorine-18-2-fluoro-D: -glucose positron emission tomography ((18)F-FDG-PET), magnetic resonance imaging (MRI), and ultrasonography. FDG uptakes in joint lesions with MESC were much higher than those reported in typical lesions of RA, suggesting that marked joint inflammation is implicated in the development of MESC.
20656619 Fatigue in systemic lupus erythematosus and rheumatoid arthritis. 2010 May Two inflammatory autoimmune diseases, systemic lupus erythematosus and rheumatoid arthritis, are characterized by fatigue. Patient reports support the significant negative impact of the symptom on functioning and well-being. The prevalence, trajectory, mechanism, and correlates of fatigue in each disease are reviewed. Some disease-focused treatments have demonstrated a reduction in fatigue. However, until recently, clinical trials have not routinely assessed fatigue. Analyses and interpretation of data have been hindered by variability in the reliability and validity of fatigue measures. Empirically based fatigue treatment guidelines are needed in both conditions.