Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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26204289 | Use of Tomosynthesis for Detection of Bone Erosions of the Foot in Patients With Establish | 2015 Aug | OBJECTIVE: The purpose of this study was to compare tomosynthesis with radiography for the detection of bone erosions of the foot in patients with established rheumatoid arthritis (RA) using MDCT as a reference standard. SUBJECTS AND METHODS: Eighteen consecutive patients with established RA were included. Each patient underwent radiography, tomosynthesis, and CT examinations of the feet on the same day. Two radiologists independently determined the number of bone erosions and the Sharp-van der Heijde score with each of the three imaging modalities. RESULTS: On a total of 216 joints from 18 patients, 216 bone erosions were detected on CT, 215 on tomosynthesis, and 181 with radiography. The mean (± SD) Sharp-van der Heijde score was equivalent for tomosynthesis (18.8 ± 16.8) and CT (19.8 ± 18.5) but was statistically lower for radiography (16.4 ± 18.0) (p = 0.030). The respective overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for tomosynthesis were 80%, 75%, 78%, 76%, and 80%, whereas the respective corresponding values for radiography were 66%, 81%, 74%, 77%, and 71%. The radiation burden of tomosynthesis was almost equivalent to that of radiography. CONCLUSION: Tomosynthesis has a higher sensitivity than radiography to detect bone erosions of the foot in patients with established RA and imparts an almost equivalent radiation burden. | |
27781272 | Gingival crevicular fluid tissue/blood vessel-type plasminogen activator and plasminogen a | 2017 Jun | BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type plasminogen activator (t-PA) and plasminogen activator inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). MATERIAL AND METHODS: Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. RESULTS: All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. CONCLUSION: In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the plasminogen activating system plays a role in the disease process of periodontitis. | |
26723864 | microRNA-126 targeting PIK3R2 promotes rheumatoid arthritis synovial fibro-blasts prolifer | 2016 Feb | OBJECTIVE: The purpose of our study was to elucidate the impact of microRNA-126 (miR-126) targeting PIK3R2 gene on cell proliferation and apoptosis of rheumatoid arthritis synovial fibro-blasts (RASFs) by regulating PI3K/AKT signal pathway. METHODS: The synovial tissue samples of this study were from 55 RA patients undergoing joint replacement and 27 healthy people undergoing joint repair due to trauma. The target genes of miR-126 were collected by the TargetScan and PIK3R2 as the direct target gene of miR-126 was confirmed by dual-luciferase reporter assay system. Our experiment had five groups including the blank control, miR-126 mimic, miR-126 mimic control, miR-126 inhibitor and miR-126 inhibitor control groups. Additionally, real-time quantitative polymerase chain reaction (RT-qPCR), Western-Blot, cell counting kit (CCK-8) and flow cytometry were carried out in this study. RESULTS: Compared with healthy individuals, the RA patients had increased miR-126, but decreased PIK3R2 mRNA expressions in the synovial tissues. Pearson correlation analysis indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (all P<0.05). When compared with the blank group respectively, the miR-126 mimic group had raising cell proportions in S and G2/M phases with reduced rate of cell apoptosis, while the miR-126 inhibitor group had raising cell proportions in G0/G1 and G2/M phases with increased rate of cell apoptosis (all P<0.05). Besides, compared with the blank control group, the miR-126 mimic group had declined expression of PIK3R2 protein with ascended expression of PI3K and p-AKT (all P<0.05), while the miR-126 inhibitor group had increased expression of PIK3R2 protein with decreased expression of PI3K and p-AKT (all P<0.05). CONCLUSION: Our study demonstrated that down-regulation of miR-126 may indirectly inhibit PI3K/AKT signaling pathway to disrupt the imbalance between growth and death of RASFs by targeting PIK3R2, which may be clinically helpful to find therapeutic strategies directed toward miR-126 function for RA patients. | |
26177310 | CD26 Expression on T Helper Populations and sCD26 Serum Levels in Patients with Rheumatoid | 2015 | We studied dipeptidyl peptidase IV (DPP-IV, CD26) expression in different T helper cells and serum soluble DPP-IV/sCD26 levels in rheumatoid arthritis (RA) patients, correlated these with disease activity score (DAS), and examined how they were affected by different therapies, conventional or biological (anti-TNF, anti-CD20 and anti-IL6R or Ig-CTLA4). The percentage of CD4+CD45R0+CD26- cells was greatly reduced in patients (up to 50%) when compared with healthy subjects. Three other subsets of CD4 cells, including a CD26high Th1-associated population, changed variably with therapies. Data from these subsets (frequency and staining density) significantly correlated with DAS28 or DAS28 components but different in each group of patients undergoing the different therapies. Th17 and Th22 subsets were implicated in RA as independent CCR4+ and CCR4- populations each, with distinct CD26 expression, and were targeted with varying efficiency by each therapy. Serum DPP-IV activity rather than sCD26 levels was lower in RA patients compared to healthy donors. DPP-IV and sCD26 serum levels were found related to specific T cell subsets but not to disease activity. We conclude that, according to their CD26 expression, different cell subsets could serve to monitor RA course, and an uncharacterized T helper CD26- subset, not targeted by therapies, should be monitored for early diagnosis. | |
27023021 | Understanding vaccination rates and attitudes among patients with rheumatoid arthritis. | 2016 Mar | OBJECTIVES: Appropriate vaccinations are important for patients with rheumatoid arthritis (RA), who are often treated with highly immunosuppressive therapies that increase their risk of infection. However, rates of vaccination among patients with RA are below optimal levels. STUDY DESIGN: We conducted a patient survey to assess self-reported vaccination status and to compare that status with electronic health record (EHR) data. METHODS: We recruited randomly selected patients with RA in an academic practice in 2013. Eligible participants had a diagnosis of RA, at least 1 visit to a rheumatology clinic in each of the previous 2 years, were 18 years or older, and had English listed as their preferred language. The survey included the following domains: a) patient self-reported receipt of influenza, pneumococcal (PNVX), and herpes zoster (HZVX) vaccinations; b) attitudes about these vaccines, including reasons for unvaccinated status, if applicable; and c) provider recommendations about these vaccines. RESULTS: Based on participants' self-report, we found a high vaccination rate for influenza during the previous season (79.4%), a moderate rate of any previous vaccination for pneumococcus (53.9%), and a very low rate of any previous vaccination for herpes zoster (7.8%). If we assume that all self-reports are accurate and we include vaccinations recorded in the EHR that were not reported by patients, the vaccination rates were approximately 8% to 9% higher for PNVX and HZVX. CONCLUSIONS: Vaccination rates are low among patients with RA based on self-report data. Further research is needed to investigate system-level barriers to vaccination and the impact of evidence-based, provider-level interventions on vaccination rates. | |
27193470 | Investigation of the human FCRL1, 2, and 4 gene expressions in patients with rheumatoid ar | 2016 Aug | The Fc receptor-like (FCRL) molecules have recently been shown to contribute to the pathogenesis of certain autoimmune disorders. In this study, we investigated the expression levels of FCRL1, 2 and 4 in blood mononuclear cells from rheumatoid arthritis patients using real-time PCR. The mRNA of these molecules was detected in 44.4Â % (FCRL1), 53.3Â % (FCRL2) and 31.1Â % (FCRL4) of patients. Comparatively, 31.1Â % (FCRL1), 51.1Â % (FCRL2) and 26.6Â % (FCRL4) of controls expressed these genes. Analysis of gene expressions in FCRL-positive patients demonstrated a lower FCRL4 gene expression in patients compared to controls (PÂ <Â 0.001). In FCRL2-positive patients, a significant positive correlation between FCRL2 expression and the erythrocyte sedimentation rate (PÂ <Â 0.001), anti-cyclic citrullinated peptide antibody (PÂ =Â 0.033) level and disease activity score (DAS28, PÂ =Â 0.016) was found. In conclusion, decreased FCRL4 expression and association of FCRL2 expression with inflammatory markers and disease activity suggested the contribution of these molecules to RA inflammatory processes. | |
26353808 | Intraindividual changes of dipeptidyl peptidase-IV in peripheral blood of patients with rh | 2015 Sep 9 | BACKGROUND: Dipeptidyl peptidase-IV (DPP-IV) is suggested to contribute to the pathogenesis of several autoimmune diseases. The aim of this study was to evaluate the association of DPP-IV presence in blood plasma and mononuclear cells with the disease activity in rheumatoid arthritis (RA). METHODS: Patients with active RA (n = 27) were examined at the study enrolment and a follow-up examination was performed after the regression of the joint effusions and at least 6 months after the first investigation. The control group comprised patients with a noninflammatory joint disease, i.e. osteoarthritis (OA; n = 15). The DPP-IV-like enzymatic activity was measured by a kinetic fluorimetric method, the concentration of DPP-IV in the blood plasma was determined using ELISA and the expression of DPP-IV in leukocytes was assayed by flow cytometry. RESULTS: Blood plasma DPP-IV-like enzymatic activity (median ± SD 220.15 ± 83.6 pkat/mL in RA vs. 376.9 ± 144.9 pkat/mL in OA, p < 0.001) and concentrations (median ± SD 465.1 ± 215.6 ng/mL in RA vs. 953.3 ± 368.4 ng/mL in OA, p < 0.001) were lower in patients with active RA compared to OA. In RA patients, the blood plasma DPP-IV-like enzymatic activity negatively correlated with the CRP concentration (r = -0.39, p = 0.044). No significant differences were observed in the DPP-IV-like enzymatic activity and DPP-IV expression in blood mononuclear cells between the RA and OA groups. At follow-up, 18 RA patients had a less active disease as demonstrated by an improved DAS28 score. In this group, comparison of the entry and the follow-up values in individual patients revealed an increase of the blood plasma DPP-IV-like enzymatic activity (median ± SD 141 ± 46% of the patient's entry values, p = 0.011) and DPP-IV concentration (median ± SD 168 ± 25%, of the patient's entry values, p = 0.033). In contrast to the blood plasma, the DPP-IV expression in blood mononuclear cells was reduced in these patients as evidenced by a decrease in the cell surface DPP-IV-like enzymatic activity as well as the median fluorescence intensity of DPP-IV staining in lymphocytes (median ± SD 66 ± 56%, p = 0.018 and 63 ± 31 % of the patient's entry values, p = 0.005, respectively). CONCLUSIONS: The association between RA activity and the changes in blood plasma and blood mononuclear cell DPP-IV in individual patients supports the possible relationship of DPP-IV to RA pathophysiology. | |
26978419 | [Trend in the prevalence of rheumatoid arthritis among the adult population in the Republi | 2015 | AIM: To analyze a trend in overall and new-onset rheumatoid arthritis morbidity among the adult population in the Republic of Kazakhstan in 2011-2012. SUBJECTS AND METHODS: The data of 2011-2012 annual statistical reports on «Population Health and Healthcare System» (Form 12) were analyzed. The indicators in the Republic of Kazakhstan were taken from the statistics digest «Population Health in the Republic of Kazakhstan and Activities of Healthcare Facilities». RESULTS: Comparative analysis of the indicators revealed an increment in overall morbidity by 1%, including that in the incidence of musculoskeletal diseases (MSD) by 3% (the increment rate per 100,000 was 2%). The rise in MSD prevalence was 20% among the adults (aged 18 years and older) and 21% among the women; the increase in the number of patients with a first established diagnosis of RA was 27% and that was 20% among the women. There was a higher rate of rises by 52 and 48% in the number of MSD patients aged 60 years and older and in that of women, respectively; the number of patients with a first established diagnosis of RA increased by 10% and that rose 12% in the women. The number of patients with a first established diagnosis of RA increased considerably by 27 and 20% among the adults aged 18 years and older) and by 10 and 12% among those aged 60 years or over, respectively. CONCLUSION: In the Republic of Kazakhstan, there is a high prevalence of MSD among people aged above 18 years and above 60 years and there is a preponderance of able-bodied persons aged 18 years or above with a first established diagnosis of RA. | |
26420577 | Optimisation of a treat-to-target approach in rheumatoid arthritis: strategies for the 3-m | 2016 Aug | BACKGROUND: Treat-to-target (T2T) is a widely accepted management strategy for rheumatoid arthritis (RA) with a key decision point at 3 months after treatment initiation. At this time point, it remains unclear which patients will benefit from treatment adaptation or from continuation of existing treatment. METHODS: We performed a pooled analysis of patient-level clinical trial data of patients with RA. We used a diagnostic testing methodology and a probabilistic approach employing logistic regression to investigate which levels of response at 3 months can inform treatment decisions in regard to achieving the target at 6 months. RESULTS: To be at least 80% sensitive for achieving the low disease activity (LDA) target at 6 months, a change at 3 months in Simplified Disease Activity Index/Clinical Disease Activity Index (SDAI or CDAI) of 58% needs to be observed at 3 months. Higher changes are needed to sensitively predict remission (REM). Not reaching the (minor) SDAI 50% response level is afflicted with very low negative likelihood ratios (LRs) (0.28 for LDA and 0.07 for REM at 6 months). Experiencing (major) SDAI 85% response has substantial positive LRs of 9.2 for reaching LDA and 6.2 for reaching REM at 6 months. In logistic regression, the change at 3 months is significantly associated with reaching of the target at 6 months. CONCLUSIONS: The 3-month time point is a critical decision point. Not achieving minor responses at 3 months makes reaching of the treatment target at 6 months highly unlikely, while reaching major responses is highly predictive of reaching the treatment target. | |
26245723 | Genetic polymorphism of 3' untranslated region of zeta-chain associated protein kinase 70 | 2016 Mar | T cell activation participates in the pathogenesis of rheumatoid arthritis (RA), and the signaling molecule zeta-chain-associated protein kinase 70 kDa (ZAP-70) plays a crucial role in this process. Different mutations in the coding sequence of ZAP-70 are involved in a variety of immunological phenotypes, and recent evidence indicates that genetic variations within the 3' untranslated regions (UTR) of microRNA binding sites may affect the hybridization with target mRNAs, leading to phenotype changes with disease status. In this study, we evaluated the possible effect of ZAP-70 polymorphism as a genetic risk factor in RA by examining the single-nucleotide polymorphism in 100 patients and 100 ethnicity- and sex-matched healthy individuals from southern Taiwan. In both groups, the genotype distribution of rs2278699 in the 3' UTR was in the Hardy-Weinberg equilibrium. In RA, there were higher frequencies of the G allele (15.5 versus 8.0 %, odds ratio 2.1, P = 0.020) and significant differences in the trend of various genotypes (P = 0.024). The results suggest that genetic polymorphism in the 3' UTR of ZAP-70 is associated with RA susceptibility in southern Taiwanese. | |
28269183 | Segmentation of the metacarpus and phalange in musculoskeletal ultrasound images using loc | 2016 Aug | This work presents a method for the automatic segmentation of metacarpus and phalange bones in ultrasound images of the second metacarpophalangeal joint (MCPJ) using Active Contours. The MCPJ is known to be the one of the first structures to be affected by rheumatic diseases like rheumatoid arthritis. The early detection and follow-up of this disease is important to prevent irreversible damage of the joints, which occurs continuously and faster if no treatment is used. To our knowledge, there is no automatic system to quantify the extension of the lesions resulting from rheumatic activity. The objective of this work is to identify the metacarpus and the phalange bones using local active contours. To our knowledge, there is no well established method for this problem and this technique has not been used yet in these structures. Results proved that the automatic segmentation is possible with an error of 3 pixels for a confidence of 80%. | |
27590013 | Use of medication reminders in patients with rheumatoid arthritis. | 2016 Nov | Patients with rheumatoid arthritis (RA) often have difficulties adhering to their medical treatment plans. We determined the characteristics of patients with RA who used reminders and the association between reminders and adherence. A total of 201 patients with RA were asked the frequency of reminders use such as pill containers, calendars, or diaries. Patients completed self-reported adherence questionnaires, and their disease activity and functional ability were measured. Sixty-eight patients (34 %) reported using a reminder. Factors associated with reminder use were older age (yes-mean age 54 vs no-mean age 49, p = 0.004), race (Whites-54 % vs Blacks-30 % vs Hispanics-26 %, p = 0.003), and sex (males-50 % vs females 28 %, p = 0.005). Working patients were less likely to use reminders (employed-21 % vs unemployed-43 %, p = 0.006). Use of calendars was associated with adherence while away from home (Ï = 0.16, p = 0.03), when busy (Ï = 0.16, p = 0.03), and use of any reminder was associated with adherence when running out of pills (Ï = 0.15, p = 0.04). The use of calendar reminders was associated with fewer tender joints (Ï = -0.17, p = 0.02). Few patients with RA used reminders, and whites, males and patients of increasing age were most likely to use reminders. Our findings show that reminders can assist patients with RA in taking medications, particularly when they are most prone to forgetting, such as when they are away from home or busy. Providers should encourage using reminders as a low-cost aid to enhance adherence. | |
26231097 | Impact of rheumatoid arthritis on career progression, productivity, and employability: The | 2016 Jan | OBJECTIVES: To evaluate the impact of rheumatoid arthritis (RA) on career, productivity, and employability. METHODS: A retrospective cross-sectional survey was conducted in 2012-2013 in France among patients with RA who were younger than 60 years of age and employed or unemployed. Patients were either recruited during a rheumatologist visit or among members of a nationwide patient-support organization (ANDAR). They completed a questionnaire on the functional impact of RA evaluated by the Health Assessment Questionnaire (HAQ) and on the impact of their disease on work ability. RESULTS: Of 488 surveyed patients, 364 (74.6%) were actively employed, 31 (6.4%) were job seekers, and 93 (19.1%) had left the workforce. In the employed group, mean age was 48.9 years; 82.1% of patients were women; mean RA duration was 11.6 years; and the HAQ score correlated strongly with various markers for decreased productivity including sick leaves, temporary or permanent work discontinuation, and having unwillingly downgraded from a full-time to a part-time work schedule or changed to a different job. Among job seekers, 54% had lost their previous job because of their RA. CONCLUSION: RA is associated with various forms of work disability, which are directly related to the severity of disease-related functional impairments. | |
25867232 | Automated Breast Volume Scanner, a new automated ultrasonic device, is useful to examine j | 2015 | OBJECTIVE: To explore the clinical application of automated scanning of wrist and finger joints by an Automated Breast Volume Scanner (ABVS) in patients with rheumatoid arthritis (RA). METHODS: A total of 140 metacarpophalangeal (MCP) joints and 28 wrist joints from the 14 active RA patients were examined by both an ABVS system (the ACUSON S2000) from dorsal sites and by conventional ultrasonography (US) from multiple directions on the same day. We used a semiquantitative scale from 0 to 3 of synovial hypertrophy and the presence of bone erosion by grayscale for both methods; the efficacy of the two methods for identifying synovial hypertrophy and bone erosion were evaluated by kappa coefficient. RESULTS: The scanning time of the ABVS was 2 min per patient and that of conventional US was 15 min per patient. The kappa coefficients of synovial hypertrophy in the MCP joints were 0.60 and 0.79 in wrist joints. These values were increased in the joints where synovial hypertrophy was moderate to severe (scores greater than 2). The kappa coefficients for the presence of bone erosion in the MCP joints were 0.74 and 0.93 in wrist joints. CONCLUSION: The present data showed a substantial agreement between ABVS and conventional US for assessments of the synovial hypertrophy and bone erosion of wrist and finger joints in patients with RA. Since ABVS can scan the wrist and finger joints automatically in a short time, ABVS is a helpful new ultrasonic method to examine joint injuries in patients with RA. | |
27580556 | AA-negative and Kappa-positive Amyloidosis in a Patient with Rheumatoid Arthritis. | 2016 | A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain. Combination therapy with high-dose melphalan and autologous stem cell transplantation was performed according to the regimen for AL amyloidosis. Her proteinuria and RA subsided, but relapsed after 3 years. This is the first report regarding kappa light chain amyloidosis in an RA patient. | |
26536782 | [GWAS of Rheumatoid Arthritis and Drug Discovery]. | 2015 Apr | We have conducted genome-wide association studies (GWAS) for rheumatoid arthritis (RA). We previously found that myelin basic protein (MBP) is associated with RA. One of the MBP isoforms (Golli-MBP) is expressed not only in nerve cells, but also in hematopoietic cells, and may negatively regulate T-cell receptor signaling. We expanded the GWAS level by collaborating with laboratories in Japan and then throughout the world. Meta-analysis of GWAS data resulted in the identification of -100 genomic loci associated with RA development. The -100 genomic loci contain -400 candidate genes, and it is not easy to find out which genes actually play important roles in RA. By incorporating available public databases, we succeeded in narrowing down the susceptibility genes from 377 to 98. We also showed that regulatory T cells are associated with RA based on the combination of the histone methylation database and our mega-GWAS results. Protein-protein interaction and drug discovery databases gave us information that some of the drugs have already been developed as therapeutic medicines for RA, and some of them were used for diseases other than RA. These drugs may be used for RA in the near future (drug repurposing). The combination of biological databases and GWAS results may be a novel method to identify new therapeutic targets. | |
27389975 | A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Art | 2016 Dec | OBJECTIVE: To compare the efficacy and safety of ABT-494, a novel selective JAK-1 inhibitor, with placebo in patients with moderate-to-severe rheumatoid arthritis (RA) and an inadequate response or intolerance to at least 1 anti-tumor necrosis factor (anti-TNF) agent. METHODS: In this 12-week, double-blind, placebo-controlled, dose-ranging study, 276 RA patients receiving a stable dose of methotrexate (MTX) who had previously received treatment with at least 1 anti-TNF agent were randomized equally to receive immediate-release ABT-494 at 3, 6, 12, or 18 mg twice daily or matching placebo twice daily. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 12. RESULTS: At week 12, significantly more patients receiving ABT-494 (53-71%) than those receiving placebo (34%) achieved an ACR20 response (by nonresponder imputation analysis) (P < 0.05), with a dose-response relationship among all ABT-494 doses (P < 0.001). ACR50 and ACR70 response rates were significantly higher in those receiving ABT-494 (36-42% and 22-26%, respectively) than in those receiving placebo (16% and 4%, respectively). Changes from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) were significantly greater for all doses of ABT-494 than for placebo (P ≤ 0.01). Onset of action of ABT-494 was rapid, with significant differences from placebo at week 2 both in ACR20 response rate (for 12 and 18 mg) and in change in the DAS28-CRP (P < 0.001 for 6-18 mg). The most frequent adverse events (AEs) were headache, nausea, upper respiratory tract infection, and urinary tract infection. Infection rates were higher at higher doses of ABT-494, but no infections were serious. No deaths were reported among those receiving ABT-494. CONCLUSION: In patients with an inadequate response or intolerance to anti-TNF agents, ABT-494 added to MTX showed rapid, dose-dependent improvements in RA signs and symptoms, with safety and tolerability similar to those of other drugs of this class. No new AEs were identified. | |
26688535 | Risk of developing active tuberculosis in rheumatoid arthritis patients on adalimumab in J | 2016 Jan | SETTING: Nationwide study in Japan. OBJECTIVE: To identify the clinical characteristics of and risk factors for tuberculosis (TB) in rheumatoid arthritis (RA) patients receiving adalimumab. DESIGN: A post hoc case-control study involving 7755 RA patients evaluated in an all-case post-marketing surveillance of adalimumab from 18 June 2008 to 20 January 2011 and spontaneous report of TB during adalimumab treatment. RESULTS: The analysis included 22 TB cases and 7733 non-TB controls. Despite the high frequency of extra-pulmonary TB (17/22, 77.3%), all 22 TB cases had pulmonary signs or symptoms. Of patients enrolled in all-case post-marketing surveillance, there were relatively high percentages of patients who had latent tuberculous infection (LTBI) at baseline. The percentage of patients who received prophylaxis was about six times higher in patients with LTBI than those without. Of those patients who received prophylaxis, none developed TB after treatment with adalimumab. Multivariate (non-matched and age-matched) and propensity score analyses identified age ⩾65 years (OR 4.59, 95%CI 1.52-13.89, P = 0.0070), moderate to severe RA (OR 4.61, 95%CI 1.07-20.00, P = 0.0408], past or current renal dysfunction (OR 4.65, 95%CI 1.47-14.71, P = 0.0089) and diabetes mellitus (OR 3.30, 95%CI 1.31-8.26, P = 0.0110) as potential risk factors for TB. CONCLUSION: Screening, prophylaxis and monitoring for TB are essential to ensure the safety of adalimumab treatment. | |
25837452 | The relationship between cervical and lumbar spine lesions in rheumatoid arthritis with a | 2015 Apr | STUDY DESIGN: A cross-sectional imaging study. OBJECTIVE: To investigate the relationship between cervical and lumbar spine lesions in patients with rheumatoid arthritis (RA), and to analyze associated factors in those with concurrent cervical and lumbar endplate erosion (EE). SUMMARY OF BACKGROUND DATA: Both the lumbar and cervical spines are often involved in RA, but little is known about the relationship between cervical and lumbar lesions. EE is often found in the spine of RA patients, but its prevalence and associated factors have not been well studied. METHODS: We enrolled 201 RA patients in this study. Cervical lesions (horizontal and vertical atlantoaxial dislocation, subaxial subluxation) and lumbar lesions (vertebral fracture, scoliosis, spondylolisthesis) were evaluated on plain radiographs. EE was evaluated on sagittal T1-weighted magnetic resonance images, and graded into 4 categories. The prevalence of each lesion was calculated, and correlations between general cervical and lumbar lesions and between cervical and lumbar EE were analyzed. To assess the clinical condition of RA, we evaluated disease duration, Steinbrocker stage, modified Stanford Health Assessment Questionnaire results, and Disease Activity Score for 28 joints with the erythrocyte sedimentation rate. Factors associated with concurrent lumbar and cervical EE were analyzed using multiple logistic regression analysis. RESULTS: Cervical lesions were found in 42.3% of patients and lumbar lesions in 56.2%. There was no significant correlation between the presence of cervical and the presence of lumbar lesions, but patients with cervical subaxial subluxation were significantly more likely to have lumbar spondylolisthesis. Cervical EE (≥1 points) was found in 61.2% of patients and lumbar EE in 39.3%. Total cervical EE score was significantly correlated with lumbar EE score. Moderate/high disease activity, Steinbrocker stage IV, and severe cervical or lumbar disk degeneration were associated with concurrent cervical and lumbar EE. CONCLUSIONS: Some cervical lesions are significantly associated with lumbar spinal lesions. Concurrent cervical and lumbar EE are related to RA disease activity and peripheral joint deterioration, suggesting that RA activity may play an important role in total spinal involvement. | |
26773110 | The Framingham Score and the Systematic Coronary Risk Evaluation at Low Cutoff Values Are | 2016 Mar | OBJECTIVE: We determined the performance of the Framingham score and the Systematic COronary Risk Evaluation (SCORE) in assessing high-risk atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: We assembled 330 cases without established cardiovascular disease (CVD), diabetes, and moderate or severe chronic kidney disease among 451 consecutive Spanish patients who underwent CVD risk screening and carotid ultrasound-determined plaque assessment. The findings were validated in 90 black and 97 white African patients. RESULTS: When sensitivity for the Framingham score was set at 80% in receiver-operator curve analysis [area under the curve (AUC) = 0.799], the corresponding cutoff value and specificity were 7.3% and 63%, respectively. At a specificity of 80%, the cutoff value and sensitivity were 10.8% and 65%, respectively. When sensitivity for SCORE (AUC = 0.747) was set at 80%, the cutoff value and specificity were 0.5% and 58%, respectively. At a specificity of 80%, the cutoff value and sensitivity were 1.5% and 50%, respectively. Upon applying a cutoff value of 7.3% for the Framingham and 0.5% for SCORE in African white patients with RA, the corresponding sensitivities and specificities were 67% and 72%, and 67% and 55%, respectively. CVD risk equations did not discriminate between black African patients with and without plaque (AUC = 0.544 and 0.549 for Framingham score and SCORE, respectively). CONCLUSION: The Framingham score and SCORE at markedly low cutoff values of 7.3% to 10.8% and 0.5% to 1.5%, respectively, can usefully estimate plaque presence in RA. Effective population-specific CVD risk assessment strategies are needed in black African patients with RA. |