Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
20698926 Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis a 2010 Dec The risk of ischaemic heart disease (IHD), and in particular myocardial infarction (MI), is increased amongst patients with established rheumatoid arthritis (RA). Few studies have included contemporary patients with RA. We recently reported that the risk of IHD is not elevated before the onset of RA symptoms. However, when, in relation to RA diagnosis, the risk is increased is unknown. OBJECTIVE: To assess the risk of MI and other IHD events amongst patients diagnosed with RA during the last decade and within 18 months following RA symptom onset, compared to the general population, by time since RA diagnosis, year of RA diagnosis and by rheumatoid factor (RF) status. METHODS AND PATIENTS: A Swedish inception cohort of RA (n = 7469) diagnosed between 1995 and 2006 and a matched general population comparator cohort (n = 37,024), was identified and linked to national registers of morbidity and mortality from IHD. Relative risks (RRs) of MI and other IHD events were estimated using Cox regression. RESULTS: During follow-up, 233 patients with RA and 701 controls developed a first MI, corresponding to an overall RR of MI of 1.6 (95% confidence interval 1.4, 1.9). Increased risks of MI were already detected within 1-4 years following RA diagnosis, as well as in patients diagnosed with RA during the last 5 years, in RF-negative patients and for transmural as well as nontransmural MIs. CONCLUSIONS: MI risk increases rapidly following RA diagnosis, suggesting the importance of additional mechanisms other than atherosclerosis. The elevated short-term risk is present amongst patients diagnosed in recent years, underscoring the importance of MI prevention from the time of RA diagnosis.
20309699 [Immunomodulatory therapy improves quality of life with rheumatoid arthritis]. 2010 May Pain, fatigue as well as functional and social impairments reduce the health-related quality of life in rheumatoid arthritis patients. Using numeric evaluations and qualitative questionnaires, it could be shown in both controlled drugs trials and in practice registries that modern drug therapy achieves an improvement in terms of quality of life (as well as in other patient-related treatment results). However, the improvements often do not achieve even the average quality-of-life levels seen in healthy people.
21128210 Quantitation of glucocorticoid receptor alpha and NF-κB pathway mRNA and its correlation 2010 Nov 23 We measured NF-κB, IKK, c-Fos, and GRα mRNA expression and in vivo glucocorticoid sensitivity in patients with rheumatoid arthritis. A very low dose intravenous dexamethasone suppression test and real-time PCR quantitation of mRNA of these genes were performed on blood samples from 21 rheumatoid arthritis patients who were not on glucocorticoids during the previous four months and on blood samples from 20 healthy individuals. Mean rheumatoid arthritis duration was 8.8 years, and mean disease activity, as assessed by Disease Activity Score 28 (DAS28), was 4.45. Basal cortisol and the percentage of cortisol reduction after the very low dose intravenous dexamethasone suppression test, as well as NF-κB, IKK, c-Fos, and GRα mRNA expression, were similar among groups. We did not observe significant correlations between glucocorticoid in vivo sensitivity and DAS28. There was a positive correlation between DAS28 and NF-κB, IKK, and GRα, but not c-Fos. In the multivariate analysis, only NF-κB mRNA remained as an independent variable for predicting DAS28.
19695389 Assessing adequate treatment response in patients with rheumatoid arthritis. 2009 Jun BACKGROUND: Rheumatoid arthritis (RA) presents a substantial socioeconomic burden that is potentially reduced by individualized, appropriate management strategies. Integral to such strategies is recognizing the need for treatment changes when patients inadequately respond or do not respond to treatment. However, there might be little or no agreement as to what constitutes treatment failure or an adequate response. Currently used American College of Rheumatology response criteria and the disease activity score may underestimate the magnitude of treatment failure when applied in clinical practice, and, having been designed to differentiate responses between large groups, they may be of limited value in monitoring individual patients. OBJECTIVE: The aim of this commentary was to assess how treatment failure and clinical remission/response have been defined in clinical studies. METHODS: A PubMed search (1948-2009) was conducted to identify clinical studies or reviews containing the following search terms: rheumatoid arthritis and treatment failure, inadequate response, biologic therapy, DMARD, radiographic response, and remission. Select clinical reports in patients with RA were included if remission or treatment failure, radiographic or other, was a study end point. RESULTS: Thirty-three studies were identified. The present assessment found no consensus as to what represents a practical definition of treatment failure or clinical remission in the clinical studies assessed. The definitions varied from the complete absence of any clinical disease to computer-generated numeric scales. The variability in clinical definitions of treatment failure or remission seems to have been mainly attributed to the time at which assessments were made, making it difficult to determine what treatment failure or remission means in individual patients with RA in clinical practice. CONCLUSIONS: Based on the findings of the present commentary, standard definitions of treatment failure or clinical remission/response are needed. Aggressive treatment strategies with specific clinical goals may result in better long-term outcomes. Early evidence of treatment effect may serve to improve clinical outcomes, including remission, and help define and align treatment goals in patients with RA.
20656069 Predictive factors of response to rituximab therapy in rheumatoid arthritis: What do we kn 2010 Oct Interest in the role of B cells in the pathogenesis of rheumatoid arthritis (RA) has increased over recent years. Rituximab (RTX), a chimeric monoclonal antibody specific for human CD20 targeting B lymphocytes, has been used to treat RA patients, and its efficacy has been clearly demonstrated in controlled clinical trials and open-label observational studies. However, it is still not known which sub-group(s) of patients will respond to RTX therapy or whether there are any factors predicting a response. The aim of this review is to discuss the most important predictive factors that are so far known. It is known that the clinical response to RTX therapy is associated with lower interferons (IFN-γ) and B-cell activating factor (BAFF) levels, the Fcγ receptor III (FcγRIII) genotype, and the C/G-174 polymorphism of interleukin 6 (IL-6); that an initial non-response to RTX depends on circulating pre-plasma cell numbers at baseline and incomplete depletion; that synovial B cells are decreased but not eliminated by RTX therapy, and that a good clinical response correlates with more substantial synovial B depletion; and, finally, that a good clinical response correlates with rheumatoid factor positivity, but not anti-cyclic citrullinated peptide antibody positivity.
20671920 Temporomandibular joint bone tissue resorption in patients with early rheumatoid arthritis 2010 The aim was to investigate whether bone tissue resorption in early RA is related to crepitus of the temporomandibular joint (TMJ) and systemic levels of inflammatory mediators and markers and sex steroid hormones. Twentynine women and 18 men with recently diagnosed RA were examined for TMJ bone erosions with computerized tomography and TMJ crepitus was assessed. Blood samples were analyzed for glutamate, 5-HT, TNF, IL-1beta, IL-6, VEGF, inflammatory markers, and estradiol, progesterone and testosterone. The TMJ erosion score was positively correlated to glutamate, and TMJ crepitus where crepitus, glutamate and ESR explained 40% of the variation in the bone erosion score. In the patients without crepitus, bone erosion score was positively correlated to glutamate, which was not the case in the patients with crepitus. In conclusion, the results of this study show that TMJ bone tissue resorption can be predicted by TMJ crepitus and glutamate in early RA.
21111289 [Pleuropulmonary involvement leading to bilateral pneumothorax in a patient being treated 2010 Nov INTRODUCTION: Rheumatoid arthritis (RA) is a systemic illness where the development of pulmonary nodule has been described in from 4 to 20% of patients. Symptomatic pleural manifestations occur in 3 to 5% of cases. Rarely, pulmonary nodules become necrotic and lead to pleural complications. Bilateral pneumothorax has only rarely been described. CASE REPORT: We report the case of a 64-year-old woman, who had been treated for RA for several years and presented with bilateral pneumothorax secondary to necrobiosis of one or several pulmonary rheumatoid nodules. The management of the pneumothorax was very prolonged and difficult, and despite surgical pleurodesis, the lung did not reexpand fully. Pathological examination of the pleura revealed a noncaseating granulomatous pattern. The diagnosis of a sarcoidosis like disease, possibly induced by anti-TNFα, or of pleural tuberculosis were suggested, but we concluded that the final diagnosis was of pleural rheumatoid involvement. CONCLUSION: Bilateral pneumothorax secondary to rheumatoid nodule is a rare entity. The management of such a complication is difficult, particularly in patients who receive an immunosuppressant regimen. A granulomatous pattern has been described rarely in the pleural tissue of these patients. Specific RA pleural involvement has to be taken in consideration when other diagnoses are eliminated, especially tuberculosis or sarcoidosis-like disease.
20124360 Genetic influences modulating the radiological severity of rheumatoid arthritis. 2010 Mar This review focuses on the contribution of genetic markers to the severity of radiological damage in rheumatoid arthritis (RA). Currently available biomarkers of more severe disease include elevated erythrocyte sedimentation rates or C-reactive protein levels and rheumatoid factor (RF) or anticyclic citrullinated protein antibodies positivity; however, these biomarkers explain a relatively modest proportion of the variance in radiological damage. An important role of genetic factors on RA severity has recently emerged but studies to date have generally been of low statistical power and many have not been replicated. Genetic markers have a number of advantages over conventional biomarkers; genotypes are stable, measurable at disease onset, remain unchanged by treatment and are amenable to high-throughput assays. The recent advances in genome-wide genetic analysis should lead to a more comprehensive understanding of RA severity genes. This knowledge could be used, along with existing biomarkers, to therapeutically target subjects at risk of poor radiological outcome.
20080387 The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis. 2010 Aug Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by a distinctive pattern of bone and joint destruction. RA patients have an increased risk of death. The incidence and prevalence of RA vary across populations, statistical methods, and disease definitions. In North America and Northern Europe, the incidence of RA is estimated at 20-50 cases per 100,000 population and the prevalence at 0.5-1.1%. Lower incidences and prevalences have been reported in Southern Europe, and few data are available for developing countries. Some studies showed declining incidences and prevalences after the 1960s. RA is a multifactorial disease that results from interactions between genetic and environmental factors. The main genetic factors are HLA-DRB1 and the tyrosine-phosphatase gene PTPN22. Among environmental factors implicated in the development of RA, smoking shows the strongest association with RA susceptibility and is also linked to worse outcomes. The aim of this review is to discuss the available data on the incidence and prevalence of RA, as well as the genetic and environmental risk factors associated with RA.
19357851 No association of PTPN22 gene polymorphism with rheumatoid arthritis in Turkey. 2009 Nov Although the association of rheumatoid arthritis (RA) with HLA-DRB1 (shared epitope) is well demonstrated in many ethnic populations, the role of other RA-associated risk loci is not clarified. In this study, the functional single nucleotide polymorphism (SNP) of PTPN22 gene was investigated in Turkey. 167 patients with RA and 177 healthy controls are genotyped by polymerase chain reaction (PCR)-RFLP for the SNP (rs2476601, A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with Xcm I enzyme. Heterozygous genotype (AG) was present in 5.1% (9/177) of the controls and in 6.6% (11/167) of RA group (p = 0.55, OR 1.3, 95% CI 0.53–3.26). There was also no association between any clinical feature, RF positivity and presence of this SNP. In conclusion, the distribution of PTPN22 polymorphism did not reveal any association with RA in Turkey.
20349068 Development of interstitial pneumonia in a patient with rheumatoid arthritis induced by is 2012 May Here, we report a 56-year-old patient with rheumatoid arthritis (RA) who had been treated with methotrexate and sulfuasalazine, but the disease activity remained high. Therefore, we planned TNF-blocker treatment for this patient. A tuberculin skin test was positive, we started anti-tuberculosis (TB) chemoprophylaxis with isoniazid (INH). However, liver dysfunction was appeared after 2 weeks from the start of INH. Therefore, we discontinued INH transiently and tried the desensitization of INH. However, interstitial pneumonia was developed 2 weeks after the re-start of INH, we decided to stop the INH prophylaxis. Interstitial pneumonia was improved by corticosteroid treatments. This case report shows that INH-induced IP can be occurred during the course of anti-TB chemoprophylaxis in patients with RA.
21210015 Gray scale and power Doppler ultrasonography in evaluation of early rheumatoid arthritis. 2010 Dec INTRODUCTION: Ultrasonography provides information regarding synovial membrane proliferation and its vascularization. The AIM of our study was to evaluate the role of gray scale and power Doppler ultrasonography in assessing early rheumatoid arthritis by analyzing the scores determined by the evaluation of synovial proliferation, joint effusion, erosion or soft tissue swelling. MATERIAL AND METHODS: The study was prospective comprising 34 patients (31 female, 3 men), mean age 45.68 years, with clinical changes and biochemical early rheumatoid arthritis. Bilateral wrist, II-V metacarpophalangeal, and proximal interphalangeal joints were evaluated by dorsal and palmar scans. RESULTS: The mean duration from the onset of symptoms was 3.46 months. Based on the clinical, biochemical and US scores the patients from our study presented early stages of RA. Also, statistically significant correlations were observed between the time elapsed from the onset, the changes highlighted by ultrasound and the stage of the disease (stage 0 or 1). CONCLUSIONS: Our study confirms that US evaluation of changes in the joints of the hand offers useful information for staging the diagnosis of RA.
20603592 [Measurement of inflammatory cytokines in patients with rheumatoid arthritis]. 2010 Jun BACKGROUND: Inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-6 play an important role in pathophysiology of rheumatoid arthritis (RA). We investigated the possibility whether TNFalpha and IL-6 could be used as an objective marker reflecting treatment response in RA. METHODS: Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) together with TNFalpha and IL-6 were measured in 159 specimens obtained from 95 RA patients. RA patients were divided into pre-treatment, methotrexate (MTX) and non-MTX groups by treatment regimen and into inactive and active groups by disease activity. The agreement between changes in marker levels and treatment response, and the correlation between each marker were analyzed. RESULTS: IL-6 was higher in active than in inactive group of patients in all three different treatment subgroups, but TNFalpha was not different between the two groups. IL-6 showed a better agreement with treatment response (MTX group, K=0.58; non-MTX group, K=0.21) than ESR or CRP, whereas TNFalpha did not show an agreement with treatment response. IL-6 was correlated with both ESR (r=0.22) and CRP (r=0.54), but TNFalpha was correlated only with ESR (r=0.21). CONCLUSIONS: Unlike TNFalpha, IL-6 reflects disease activity of RA and shows a better agreement with treatment response than ESR or CRP, indicating that it has an association with clinical features of RA. Therefore IL-6 could be used as an additional marker in the evaluation of treatment response when markers like ESR or CRP show results discordant from clinical features.
20693274 Decrease in sick leave among patients with rheumatoid arthritis in the first 12 months aft 2010 Dec OBJECTIVE: To investigate the effect of tumour necrosis factor (TNF) antagonist treatment of patients with rheumatoid arthritis (RA) on sick leave (SL) and disability pension (DP) in a population-based setting in southern Sweden. METHODS: All patients with RA in the South Swedish Arthritis Treatment Group register living in the county of Skåne (population 1.2 million), who started their first treatment with a TNF antagonist between January 2004 and December 2007 and were 18-58 years at treatment start (n = 365), were identified. For each patient with RA, four matched reference subjects from the general population were randomly selected. Data were linked to the Swedish Social Insurance Agency register and the point prevalence of SL and DP as well as days of SL and DP per month were calculated from 360 days before until 360 days after treatment start. RESULTS: At treatment start 38.6% of the patients with RA were registered for SL. During the first 6 months this share dropped to 28.5% (decrease by 26.2%, p< 0.001). This level remained stable throughout the first treatment year. Comparing patients with RA to the reference group the relative risk of being on SL was 6.6 (95% CI 5.2 to 8.5) at initiation of anti-TNF treatment and 5.2 (95% CI 4.0 to 6.8) 1 year after that. The corresponding figures for DP were 3.4 (95% CI 2.7 to 4.2) and 3.2 (95% CI 2.7 to 3.9). CONCLUSIONS: There was a marked decline in SL during the first 6 months of TNF antagonist treatment in patients with RA in southern Sweden, maintained throughout the first year, which was not offset by a corresponding increase in DP.
19457255 Discriminant validity, responsiveness and reliability of the rheumatoid arthritis-specific 2009 INTRODUCTION: The rheumatoid arthritis-specific Work Productivity Survey (WPS-RA) measures the impact of rheumatoid arthritis (RA) and treatment on patient productivity within and outside the home. It contains nine questions addressing employment status, productivity within and outside the home, and daily activities. The objective of this paper was to evaluate the discriminant validity, responsiveness, and reliability of the WPS-RA in patients with active RA. METHODS: Two hundred twenty subjects (mean age was 53.8 years, 83.6% were female, mean disease duration was 9.54 years, mean number of disease-modifying anti-rheumatic drugs failed was 2, and 38.6% were employed outside the home) in a phase III, 24-week, double-blind, placebo-controlled trial completed the WPS-RA at baseline and every 4 weeks until withdrawal/study completion. Validity was evaluated via known groups using baseline data (first and third quartiles of subjects' Health Assessment Questionnaire--Disability Index [HAQ-DI] scores and Short Form-36 health survey [SF-36] scores). To evaluate responsiveness, mean changes in WPS-RA at week 24 were compared between American College of Rheumatology 20% improvement criteria (ACR20) (or HAQ-DI) responders and non-responders. Standardized response mean (SRM) was also used to quantify responsiveness. All group comparisons were conducted using a non-parametric bootstrap-t method. RESULTS: Subjects with lower HAQ-DI or SF-36 scores generally had statistically greater RA-associated losses in productivity within and outside the home compared with subjects with higher scores (25 of 32 evaluations were statistically significant). Smallest differences between groupswere seen in work absenteeism and days with outside help. At week 24, ACR20 and HAQ-DI responders reported large improvements in productivity within and outside the home; non-responders reported mainly a worsening in productivity (P
20506175 Psychological interventions for rheumatoid arthritis: examining the role of self-regulatio 2010 Oct OBJECTIVE: To examine the efficacy of psychological interventions for rheumatoid arthritis (RA), and to determine whether self-regulation interventions demonstrate efficacy superior to that of other psychological treatments. METHODS: Only randomized controlled trials testing a face-to-face psychological intervention among patients with RA were included. Two independent investigators extracted pertinent study data, rated each study on a scale of methodologic quality, and assessed each treatment condition for its inclusion of 5 behavior-change techniques derived from self-regulation theory (goal setting, planning, self-monitoring, feedback, and relapse prevention). RESULTS: Twenty-seven trials were included, and cumulative effect sizes were calculated for the 5 outcomes. Significant effect sizes (Hedges' g) were found at posttreatment for physical activity (0.45), pain (0.18), disability (0.32), depressive symptoms (0.23), and anxiety (0.17). At followup (range 2-14 months), significant effect sizes were obtained for physical activity (0.36), pain (0.13), disability (0.15), and depressive symptoms (0.32). Comparative analyses revealed that interventions utilizing more self-regulation techniques reduced depressive symptoms and anxiety significantly more than interventions utilizing fewer such techniques. Additionally, depressive symptoms were reduced significantly more among recently diagnosed RA patients than among those with longstanding RA. CONCLUSION: Psychological interventions are beneficial for many patients with RA, particularly when it comes to increasing physical activity levels. Intervention techniques derived from self-regulation theory appear to play a role in reducing depressive symptoms and anxiety among patients with RA.
19823836 Diagnostic value of synovial fluid anti-cyclic citrullinated peptide antibody for rheumato 2010 Sep Early and accurate diagnosis and treatment of rheumatoid arthritis (RA) improves disease outcome. Anti-cyclic citrullinated peptide antibody (anti-CCP) which is highly specific for RA is produced locally from inflamed synovium. The present study was designed to assess the diagnostic performance of synovial fluid anti-CCP (sf-CCP) for RA. A total of 128 patients consisted of 37 RA confirmed by the American College of Rheumatology revised criteria, 91 non-RA (50 non-RA inflammatory arthritis and 41 osteoarthritis) entered the study. Serum anti-CCP (sm-CCP) and Sf-CCP were measured by the ELISA method. Receiver operating characteristics curves were constructed to determine the optimal cutoff point levels for sf-CCP and sm-CCP to discriminate RA from non-RA. Diagnostic characteristics of both variables were determined by comparison of RA patients with non-RA controls. Mean levels of sf-CCP and sm-CCP were significantly higher in RA than in non-RA (P < 0.001). Sf-CCP discriminated RA from non-RA at the optimal cutoff value of 10 U/mL with high accuracy at AUC value of 0.897 +/- 0.039, P < 0.001) sensitivity of 83.7% and specificity of 95.6%. Sm-CCP diagnosed RA at optimal cutoff level of 14.6 U/mL with respective sensitivity, specificity and AUC values of 84.8, 94.3% and 0.895 +/- 0.049, P < 0.001). Sm-CCP was strongly correlated with sf-CCP (r = 0.75, r (2) = 0.57, P < 0.0001). Two of 5 sm-CCP negative RA and 25.7% of serum rheumatoid factors negative RA were sf-CCP positive. These findings indicate that sf-CCP yields diagnostic ability as comparable as sm-CCP for RA. Respecting to local production of sf-CCP prior to disease onset, therefore sf-CCP determination may offer earlier as well as additional diagnostic information which may be more helpful in recognizing RA particularly among recent onset arthritis.
20966863 Self-helplessness in arthritis: an important but overlooked index. 2010 Aug 12 The recent introduction of patient-reported outcome measures (PROMs) assessment into rheumatology practice has changed the way patients suffering from inflammatory arthritis are assessed. This article describes a cross-sectional study of 102 rheumatoid arthritis (RA) patients that was undertaken to evaluate the construct of helplessness in patients with RA, its correlation with other disease activity parameters, and its sensitivity to change following biologic therapy. The study also set out to explore the possibility of including a self-helplessness measurement, using the modified Rheumatology Attitude Index (mRAI), as part of the holistic patient assessment in standard clinical practice. Assessment of self-helplessness was shown to be significantly correlated with both psychological as well as functional status measures. The mRAI index is a highly useful and predictive tool for clinical use that is responsive to change in the patients' clinical condition. As part of the PROMs questionnaire, this scale can be applied in a manner similar to other indicators of disease activity status, and is as easy to administer and interpret in standard clinical practice.
20603497 Common vaccinations among adults do not increase the risk of developing rheumatoid arthrit 2010 Oct OBJECTIVE: To investigate the association between vaccinations in adults and the risk of developing rheumatoid arthritis (RA). METHODS: Data from the Swedish population-based Epidemiological Investigation of RA case-control study encompassing 1998 incident cases of RA aged 18-70 years and 2252 randomly selected controls matched for age, sex and residency were analysed. Those vaccinated within 5 years before disease onset were compared with those not vaccinated by calculating OR with 95% CI. RESULTS: Vaccinations neither increased the risk of RA overall (OR 1.0, 95% CI 0.9 to 1.1) nor the risk of two major subgroups of RA (antibodies to citrullinated peptide-positive (ACPA-positive) and ACPA-negative disease). Furthermore, vaccinations did not increase the risk of RA in smokers or carriers of HLA-DRB1 shared epitope alleles, two groups with established risk factors for RA. CONCLUSIONS: In this case-control study of incident cases of newly diagnosed RA, no increased risk of RA following immunisation was observed for vaccinations overall or for any specific vaccination. This indicates that immunological provocation of adults with commonly used vaccines in their present form carries no risk of RA. These findings should be implemented among public healthcare providers in order to encourage vaccinations according to recommended national vaccination schedules.
19404938 Rheumatoid arthritis joint progression in sustained remission is determined by disease act 2009 May OBJECTIVE: Joint damage is related to disease activity in rheumatoid arthritis (RA), but the degree of its progression and the temporal associations between disease activity and joint damage are unclear. The aim of this study was to evaluate whether there is a latency in the effect of disease activity on radiographic progression in patients with RA. METHODS: Data were obtained from the PREMIER trial, a 2-year randomized, controlled clinical trial of adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in early RA. Radiographic progression of joint damage was calculated using the modified total Sharp score in a subset of patients whose disease was in remission (Simplified Disease Activity Index