Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
25550338 | Changes in the anticitrullinated peptide antibody response in relation to therapeutic outc | 2016 Feb | OBJECTIVE: To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA). METHODS: Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and α-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression. RESULTS: During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression. CONCLUSIONS: The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA. TRIAL REGISTRATION NUMBER: WHO database at the Karolinska institute: CT20080004; and clinicaltrials.gov: NCT00764725. | |
26052885 | Lived Experiences of Sex Life Difficulties in Men and Women with Early RA - The Swedish TI | 2015 Dec | BACKGROUND: Men and women with rheumatoid arthritis (RA) experience restrictions in everyday life, in spite of the development of new medications. Recent research has described in detail how participation limitations are experienced in everyday life from a patient perspective. However, knowledge of how sex and intimate relationships are affected is still scarce. OBJECTIVES: The aim of the present study was to explore sex life experiences in relation to sexual function and sexual relationships in men and women with early RA. METHODS: The study formed part of TIRA-2 (the Swedish acronym for the prospective multicentre early arthritis project). The data collection included 45 interviews with 21 men and 24 women, aged 20-63, which were recorded and transcribed verbatim. The critical incident technique was used to collect data, and content analysis to categorize the results. RESULTS: Half the participants stated that RA affected their sex life. The general descriptions formed five categories: sex life and tiredness; sex life and ageing; emotional consequences of impaired sexual function; facilitators of sexual function and sexual relationships; and strain on the sexual relationship. CONCLUSIONS: Sex life is affected in early RA, in spite of new effective treatment strategies. New strategies of communication, assessment and self-managing interventions concerning the sex lives of patients with RA need to be implemented by a multidisciplinary healthcare team. Copyright © 2015 John Wiley & Sons, Ltd. | |
25947325 | Physical activity and the association with fatigue and sleep in Danish patients with rheum | 2015 Oct | The aim of this study was to examine physical activity behavior in patients with rheumatoid arthritis and to identify potential correlates of regular physical activity including fatigue, sleep, pain, physical function and disease activity. A total of 443 patients were recruited from a rheumatology outpatient clinic and included in this cross-sectional study. Physical activity was assessed by a four-class questionnaire, in addition to the Physical Activity Scale. Other instruments included the Multidimensional Fatigue Inventory (MFI), the Pittsburgh Sleep Quality Index and the Health Assessment Questionnaire. Disease activity was obtained from a nationwide clinical database. Of the included patients, 80 % were female and mean age was 60 (range 21-88 years). Hereof, 22 % (n = 96) were regularly physically active, and 78 % (n = 349) were mainly sedentary or having a low level of physical activity. An inverse univariate association was found between moderate to vigorous physical activity, and fatigue (MFI mental, MFI activity, MFI physical and MFI general), sleep, diabetes, depression, pain, patient global assessment, HAQ and disease activity. The multivariate prediction model demonstrated that fatigue-related reduced activity and physical fatigue were selected in >95 % of the bootstrap samples with median odds ratio 0.89 (2.5-97.5 % quantiles: 0.78-1.00) and 0.91 (2.5-97.5 % quantiles: 0.81-0.97), respectively, while disease activity was selected in 82 % of the bootstrap samples with median odds ratio 0.90. Moderate to vigorous physical activity in patients with rheumatoid arthritis is associated with the absence of several RA-related factors with the most important correlates being reduced activity due to fatigue, physical fatigue and disease activity. | |
27388027 | Psoriasis, psoriatic arthritis, and rheumatoid arthritis: Is all inflammation the same? | 2016 Dec | OBJECTIVES: To review the pathophysiology, co-morbidities, and therapeutic options for psoriasis, psoriatic arthritis and rheumatoid arthritis in order to further understand the similarities and differences in treatment paradigms in the management of each disease. New targets for individualized therapeutic decisions are also identified with the aim of improving therapeutic outcome and reducing toxicity. SEARCH STRATEGY: Using the PubMed database, we searched literature published from 2000 to 2015 using combinations of the key words "psoriasis," "psoriatic arthritis," "rheumatoid arthritis," "pathogenesis," "immunomodulation," and "treatment." INCLUSION AND EXCLUSION CRITERIA: This was a non-systematic review and there were no formal inclusion and exclusion criteria. DATA EXTRACTION: Abstracts identified in the search were screened for relevance and articles considered appropriate evaluated further. References within these selected articles were also screened. Information was extracted from 198 articles for inclusion in this report. DATA SYNTHESIS: There was no formal data synthesis. Articles were reviewed and summarized according to disease area (psoriasis, psoriatic arthritis, and rheumatoid arthritis). HEADLINE RESULTS: The pathophysiology of psoriasis, psoriatic arthritis, and rheumatoid arthritis involves chronic inflammation mediated by pro-inflammatory cytokines. Dysfunction in integrated signaling pathways affecting different constituents of the immune system result in varying clinical features in the three diseases. Co-morbidities, including cardiovascular disease, malignancies, and non-alcoholic fatty liver disease are increased. Increased understanding of the immunopathogenesis allowed development of targeted treatments; however, despite a variety of potentially predictive genetic, protein and cellular biomarkers, there is still significant unmet need in these three inflammatory disorders. | |
26886389 | Computed tomography of pulmonary changes in rheumatoid arthritis: carcinoembryonic antigen | 2016 Apr | Rheumatoid arthritis (RA) classically affects the joints, but can present extra-articular manifestations, including pulmonary disease. The present study aimed to identify possible risk factors or laboratory markers for lung involvement in RA, particularly the presence of rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and tumor markers, by correlating them with changes observed on chest high-resolution computerized tomography (HRCT). This cross-sectional study involved RA patients who were examined and questioned by a specialist physician and later subjected to chest HRCT and blood collection for measurement of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), ACPA (anti-vimentin and/or anti-CCP3), and the tumor markers carcinoembryonic antigen (CEA), CA 125, CA 15-3, and CA 19-9. A total of 96 patients underwent chest HRCT. The most frequent findings were bronchial thickening (27/28.1 %) and bronchiectasis (25/26 %). RF was present in 63.2 % of patients (55/87), and ACPA (anti-vimentin or anti-CCP3) was present in 72.7 % of patients (64/88). CEA levels were high in 14 non-smokers (37.8 %) and 23 smokers (62.2 %). CA-19-9 levels were high in 6 of 86 patients (7.0 %), CA 15-3 levels were high in 3 of 85 patients (3.5 %), and CA 125 levels were high in 4 of 75 patients (5.3 %). Multivariate analysis indicated a statistically significant association between high CEA levels and the presence of airway changes in patients with RA (p = 0.048). CEA can serve as a predictor of lung disease in RA and can help identify individuals who require more detailed examination for the presence of respiratory disorders. | |
26712845 | Fit for work? Evaluation of a workshop for rheumatology teams. | 2016 Jun | BACKGROUND: People with rheumatoid arthritis (RA) may rapidly cease work prematurely due to ill-health. A recent survey noted that a quarter of respondents with RA experienced job loss within a year of diagnosis and 50% stopped work within 6 years. AIMS: To develop and pilot workshops to increase the knowledge, skills and confidence of rheumatology team members to support work-related issues in outpatient clinics. METHODS: A 3-h interactive workshop, informed by rheumatology experts and the Royal College of General Practitioners (RCGP) National Education Programme (NEP) about work and health, was developed to address both knowledge and skills in the management of health and work consultations in an outpatient setting. Questionnaires were developed for use pre- and immediately post-workshop, with questions that focused on the confidence of delegates in managing these discussions and the importance they placed upon them. RESULTS: Ninety-nine participants attended five workshops throughout the UK between 2013 and 2104. Seventy-three per cent (72) completed the post-workshop questionnaire. Eighty-nine per cent found the workshop useful or very useful, 88% found it relevant or very relevant and 79% responded that it had an impact or a considerable impact on their practice. Wilcoxon matched pairs signed rank tests were carried out that showed an overall increase in confidence after training. CONCLUSIONS: The results suggest that the workshop was both relevant and useful to participants and had an impact on their practice. This was true for all specialities. The workshops also highlighted participants' desire to understand how to use the 'fit note' to enhance their patient management. | |
25836639 | Lung disease in rheumatoid arthritis. | 2015 May | Rheumatoid arthritis (RA) affects approximately 1% of the US population frequently has extra-articular manifestations. Most compartments of the lung are susceptible to disease. Interstitial lung disease (ILD) and airways disease are the most common forms of RA-related lung disease. RA-ILD carries the worst prognosis and most often manifests in a histologic pattern of usual interstitial pneumonia or nonspecific interstitial pneumonia. There have been no large, well-controlled prospective studies investigating therapies for RA-ILD. Treatment usually entails immunomodulatory agents. Further studies are needed to better understand pathogenic mechanisms of disease that lead to lung involvement in these patients. | |
25326335 | Meta-analysis of associations between functional HLA-G polymorphisms and susceptibility to | 2015 Jun | The aim of this study was to determine whether the functional HLA-G 14 bp insertion (I)/deletion (D) and +3142 G/C polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the HLA-G 14 bp I/D, and +3142 G/C polymorphisms and SLE or RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of 14 comparison studies from 11 articles met our inclusion criteria, comprising eight on SLE (1,284 patients and 1,885 controls) and four on RA (820 patients and 772 controls), and three studies investigated response to methotrexate (MTX) in RA according to the HLA-G 14 bp I/D polymorphisms (249 responders and 205 nonresponders). Meta-analysis revealed an association between the II + ID genotype of the HLA-G 14 bp I/D polymorphism in overall group (OR = 1.205, 95% CI = 1.036-1.403, P = 0.016). Ethnicity-specific meta-analysis showed no association between the II + ID genotype and SLE in the South American, European, and Asian population. Meta-analysis revealed a significant association between SLE and the HLA-G +3142 G allele in all study subjects (OR = 1.367, 95% CI = 1.158-1.613, P = 2.2 × 10(-5)) and in the South American group (OR = 1.531, 95% CI = 1.242-1.888, P = 6.7 × 10(-5)). However, no association between HLA-G 14 bp I/D, and +3142 G/C polymorphisms and RA was found (OR for HLA-G I allele = 1.013, 95 % CI = 0.879-1.167, P = 0.859; OR for +3142 G allele = 0.980, 95% CI = 0.742-1.294, P = 0.888). Furthermore, HLA-G 14 bp I/D polymorphism was not found to be associated with response to MTX in RA. This meta-analysis demonstrates that the HLA-G 14 bp I/D polymorphism is associated with susceptibility to SLE, and HLA-G +3142 G/C polymorphisms are associated with susceptibility to SLE in South Americans. | |
25664400 | Adverse events and infections in patients with rheumatoid arthritis treated with conventio | 2015 Mar | OBJECTIVES: Treatment of rheumatoid arthritis (RA) with disease-modifying anti-rheumatic drugs (DMARDs), either synthetic (sDMARDs) or biologic agents (bDMARDs) has significantly improved disease outcome. However, the impact of therapy-related adverse events (AEs), mild, moderate or serious, on disease outcome is under debate. The purpose of the study was to test the hypothesis that AEs, including infections, are rather common in patients receiving bDMARDs than in those receiving sDMARDs. METHODS: Analysis of the medical records of patients followed in a single outpatient clinic was performed. In total, 1403 adults (295 men, 1108 women) were included in the analysis (969 treated with sDMARDs only, 434 with bDMARDs). All AEs and infections were recorded and their severity was graded according to international criteria. Incident rates were calculated and Kaplan-Meier plots as well as Cox proportional-hazards models were performed to examine the association of treatment groups with the risk of any AE. RESULTS: The risk of any AE, irrespective of severity, was significantly higher in patients with bDMARDs with the adjusted hazard ratio being 1.98 (95% CI: 1.64 to 2.39). Patients in the biologic group treated initially with infliximab or adalimumab had a higher risk of AE compared to patients receiving etanercept or other biologic agents. Among patients treated with methotrexate, those receiving a dose below 10 mg had a higher risk of any AE when compared to those receiving higher doses. CONCLUSIONS: The risk of any AE among RA patients treated with bDMARDs was significantly higher compared to those treated with sDMARDs. | |
26000294 | Isotypes of Epstein-Barr virus antibodies in rheumatoid arthritis: association with rheuma | 2015 | In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE), and 28 healthy controls (HCs) were investigated by enzyme-linked immunosorbent assays (ELISA). Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1) were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD) were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs, IgG) and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection). Notably, for IgM and IgA (but not IgG), these were associated with the presence of characteristic RA autoantibodies. | |
26364962 | [Cardiovascular disease and systemic inflammatory diseases]. | 2016 Mar | More than a century of research has shown that atherosclerosis is an inflammatory process more than an infiltrative or thrombogenic process. It has been demonstrated epidemiologically and by imaging techniques, that systemic inflammatory diseases (in particular, but not exclusively, rheumatoid arthritis and systemic lupus erythematosus) increase the atherosclerotic process, and has a demonstrated pathophysiological basis. Furthermore, treatments to control inflammatory diseases can modify the course of the atherosclerotic process. Although there are no specific scales for assessing cardiovascular risk in patients with these diseases, cardiovascular risk is high. A number of specific risk scales are being developed, that take into account specific factors such as the degree of inflammatory activity. | |
25581505 | Continued participation in a ten-year tight control treat-to-target study in rheumatoid ar | 2015 May | OBJECTIVE: To identify risk factors for early study termination and motivators for adherence to a long-term followup trial and to improve completeness of long-term studies. METHODS: Risk factors for early termination in 508 included patients were identified through Cox regression analysis. Patients completing the 10-year followup filled in a questionnaire on possible motives for continued study participation. RESULTS: Risk factors for early termination were higher age (hazard ratio [HR] 1.03, 95% confidence interval [95% CI] 1.02-1.04), functional disability during the preceding year (HR 1.54, 95% CI 1.20-1.99), having achieved drug-free remission (HR 6.62, 95% CI 2.07-21.14), limited joint damage (HR 0.98, 95% CI 0.97-0.995 for actual damage; HR 0.83, 95% CI 0.73-0.94 for damage progression), and few adverse events (HR 0.35, 95% CI 0.26-0.47). A total of 288 of 313 patients (92%) attending the last visit answered the questionnaire. The majority mentioned contributing to scientific research (97% agreed), helping other patients (91%), and learning about new treatment strategies (84%) and their disease (85%) as reasons to continue participation. Next, patients mentioned tight control (202 of 278 patients), good treatment strategy (128 of 278), good medication (117 of 278), and good half-term results (102 of 278) as motivators. More than 95% of patients experienced participation "as expected" or "better than expected." Additional examinations during yearly visits (extra questionnaires, imaging) were mentioned as "worse than expected" (10%), as was answering routine questionnaires (7%). CONCLUSION: Continued participation was relatively high in the Treatment Strategies for Rheumatoid Arthritis (BeSt) Study. Higher age, functional disability, drug-free remission, little joint damage, and few adverse events predicted early study termination. Main motives for continued participation were a willingness to contribute to research, help future patients, and because patients had good experiences with the study protocol. | |
25758991 | A gene-based information gain method for detecting gene-gene interactions in case-control | 2015 Nov | Currently, most methods for detecting gene-gene interactions (GGIs) in genome-wide association studies are divided into SNP-based methods and gene-based methods. Generally, the gene-based methods can be more powerful than SNP-based methods. Some gene-based entropy methods can only capture the linear relationship between genes. We therefore proposed a nonparametric gene-based information gain method (GBIGM) that can capture both linear relationship and nonlinear correlation between genes. Through simulation with different odds ratio, sample size and prevalence rate, GBIGM was shown to be valid and more powerful than classic KCCU method and SNP-based entropy method. In the analysis of data from 17 genes on rheumatoid arthritis, GBIGM was more effective than the other two methods as it obtains fewer significant results, which was important for biological verification. Therefore, GBIGM is a suitable and powerful tool for detecting GGIs in case-control studies. | |
25943629 | Is the state of health of rheumatoid arthritis patients receiving adequate treatment, pred | 2015 May 6 | BACKGROUND: A survey was conducted to evaluate whether a steady improvement in the quality of life of Rheumatoid Arthritis (RA) patients as frequently reported in clinical studies, does actually occur. The focus of this study laid on the personal perception of RA patients. How do patients who have been treated along accepted guidelines see the state of their health and their joint pain at different points in time? METHODS: RA patients were asked to complete a questionnaire and return it to an opinion research centre. The questionnaire, which was developed by the authors, was divided into the areas: demography, symptom description and medical care, as well as the illness in a personal context. Three telephone interviews followed in monthly intervals when the patients' feelings about their illness, their every-day coping mechanisms and their social lives were rated. Intra-subject correlation and the level of agreement among patients when assessed at three different points within a two month period, was determined. RESULTS: 127 patients replied to the questionnaire. RA exerts a significant impact on a patient's daily life. Average ratings of current state of health and joint pain (answered on a 5-part scale extending from 1 (very good) to 5 (very bad)) range between 2.6 and 2.9 all three times. However, intra-subject correlation between the different assessment times, is in general quite modest. Concerning the question: "How is your join pain today?" only 14 of 127 participants express identical ratings all three times , while in one third of the participants, a difference of two digits on the 5-part scale, at least twice had to be noticed. Intra-class correlation coefficients between answers at different points are often much smaller than 0.5. Results were similar in all subgroups analysed (men vs. women; patients receiving biologics vs. those not receiving biologics; disease duration ≤3 years vs. 4 to 10 years vs. ≥11 years). CONCLUSION: On an individual level personal assessments of health, well-being and joint pain are nevertheless unsteady even within the timeframe of two months. This is why, even now, RA patients still cannot plan their lives as non-affected people can. | |
25983292 | [The role of the PD-1 protein in pathogenesis of autoimmune diseases, with particular cons | 2015 Apr 28 | Polymorphism of the PDCD1 gene for the PD-1 protein (programmed cell death 1, encoded by PDCD1) is significantly associated with higher incidence of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), which may suggest the participation of PD-1 in the pathogenesis of these diseases. Over 30 single nucleotide polymorphisms (SNPs) have been identified in the human PDCD1 gene. SNPs in the PDCD1 gene in humans have demonstrated relevant associations with a higher risk of developing autoimmune diseases in certain ethnic groups. RA and SLE are chronic connective tissue diseases with autoimmune background. RA is a common form of chronic, progressive arthritis in adults. SLE is characterized by chronic inflammation in most of the body's tissues and organs, leading to a complex clinical syndrome. The pathogenesis of the autoimmune diseases is not well examined. However, genetic factors, immunological disorders and environmental factors are believed to play a decisive role in the occurrence of the illnesses. Complex immune system disorders are responsible for the development of SLE. In RA activated T cells produce cytokines such as interleukin 2 (IL-2) and interferon γ (IFN-γ) that stimulate macrophages and monocytes. The main role of PD-1 is inhibition of T-cell proliferation, inhibition of production of IL-2, interleukin 10 (IL-10) and IFN-γ, and inhibition of activation of autoreactive lymphocytes. Because of the wide range of ligand distribution in the body, the biological significance of protein refers to almost all aspects of the immune response, including autoimmunology, tumour immunology, inflammation, transplantation, and allergy. Currently, there is increasing interest in the importance of PD-1 in the maintenance of immunological balance and its role in the development of autoimmune diseases. We summarize the PD-1 research in patients with RA and SLE in recent years. | |
25885521 | Results of a proof of concept, double-blind, randomized trial of a second generation antis | 2015 Mar 19 | INTRODUCTION: This randomized, double-blind, phase II study evaluated the pharmacodynamics, safety and tolerability of ISIS 329993 (ISIS-CRPRx), an antisense oligonucleotide, in patients with active rheumatoid arthritis (RA). METHODS: Patients with active RA of at least six months duration were randomized into three cohorts to receive ISIS-CRPRx (100 mg, 200 mg or 400 mg) or placebo (3 active:1 placebo within each cohort) via subcutaneous (SC) injection on Days 1, 3, 5 and 8 and then once weekly for the next 11 weeks. The effects of study treatment on high-sensitivity C-reactive protein (hs-CRP) level were evaluated. An exploratory analysis on disease activity was assessed via the American College of Rheumatology 20% improvement criteria (ACR20). Safety was evaluated via adverse events and laboratory measures. RESULTS: Fifty-one patients received one of the following treatments: ISIS-CRPRx 100 mg, n = 12; 200 mg, n = 13, 400 mg, n = 14; placebo n = 12. In the ISIS-CRPRx treatment groups there were dose-dependent reductions in hs-CRP. At Day 36 the mean percent change from baseline was: placebo: -14.4%; ISIS-CRPRx 100 mg: -19.5%; 200 mg: -56.6% and 400 mg: -76.7%, (P = 0.0015 placebo compared to 400 mg). There were no differences between treatment groups and placebo in the ACR20 at Day 36 or Day 92. There were no serious infections and no elevations in liver function tests, lipids, creatinine or other lab abnormalities related to ISIS-CRPRx. CONCLUSIONS: In this study, ISIS-CRPRx selectively reduced hs-CRP in a dose-dependent manner, and was well-tolerated in patients with RA. Its utility as a therapy in RA remains unclear. TRIAL REGISTRATION: Clinicaltrials.gov NCT01414101 . Registered 21 July 2011. | |
26950411 | Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. | 2016 Aug | Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J mice were divided into four groups: control, zoledronic acid (ZA), collagen-induced arthritis (CIA), and CIA-ZA. Animals were pretreated with vehicle or ZA. Bovine collagen II emulsified in Freund's adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8 weeks. ONJ indices were measured by micro-CT (µCT) and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by µCT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, periodontal ligament (PDL) space widening, lamina dura loss, and cortex thinning. ZA prevented these changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development. © 2016 American Society for Bone and Mineral Research. | |
26754747 | Socioeconomic factors and self-reported health outcomes in African Americans with rheumato | 2016 Jan 12 | BACKGROUND: There is abundant evidence that low socioeconomic status (SES) is associated with worse health outcomes among people with Rheumatoid Arthritis (RA); however, the influence of socioeconomic disadvantage in early life has yet to be studied within that population. METHODS: Data originated from the cross-sectional arm of the Consortium Evaluation of African-Americans with Rheumatoid Arthritis (CLEAR II), which recruited African-Americans with RA from six sites in the Southeastern United States. We used linear regression models to evaluate associations of parental homeownership status and educational level at participant time of birth with participant-reported fatigue (Visual Analog scale, cm), pain (Visual Analog scale, cm), disability (Health Assessment Questionnaire) and helplessness (Rheumatology Attitudes Index), independently of participant homeownership status and educational level. Models included random effects to account for intra-site correlations, and were adjusted for variables identified using backward selection, from: age, disease-duration, sex, medication use, body-mass index, smoking history. RESULTS: Our sample included 516 CLEAR II participants with full data on demographics and covariates. 89% of participants were women, the mean age was 54.7 years and mean disease duration was 10.8 years. In age adjusted models, parental non-homeownership was associated with greater fatigue (β = 0.75, 95% CI = 0.36-1.14), disability (β = 0.12, 95% CI = 0.04-0.19) and helplessness (β = 0.12, 95% CI = 0.03-0.21), independently of participant homeownership and education; parental education had a further small influence on self-reported fatigue (β = 0.20, 95% CI = 0.15-0.24). CONCLUSIONS: Parental homeownership, and to a small extent parental education, had modest but meaningful relationships with self-reported health among CLEAR II participants. | |
27607196 | Clinical, radiographic and functional efficacy of abatacept in routine care for rheumatoid | 2016 Sep | OBJECTIVES: To investigate the efficacy and safety of abatacept for treating patients with rheumatoid arthritis (RA) in routine clinical practice and to determine the prognostic factors affecting clinical outcomes. METHODS: We performed a retrospective study of 194 RA patients treated with abatacept. Clinical outcomes at 1 year after the treatment were assessed. Joint damage was assessed by the van der Heijde-modified total Sharp score (mTSS). RESULTS: Of the 194 patients, abatacept was discontinued in 51 patients, resulting in a retention rate at week 52 of 73.7%. At week 52, 23.7% of patients achieved clinical remission (SDAI ≤3.3). Lower SDAI and higher RF titre at baseline were the prognostic factor for SDAI at 52 weeks. Structural remission (ΔmTSS ≤0.5) was achieved in 73.4% of patients. However, clinical relevant radiographic progression which was defined as an increase in ΔmTSS >3 in a year, occurred in 7.6% of patients. Likewise, rapid radiological progression, which was defined as an increase in ΔmTSS >5 in a year, was observed in 6.4% of patients. 16.5% of patients achieved comprehensive disease remission, which was defined as SDAI ≤3.3, HAQ-DI ≤0.5, ΔmTSS ≤0.5, while 22.4% of patients achieved comprehensive disease control (CDC), which was defined as SDAI ≤11.0, HAQ-DI ≤0.5, ΔmTSS ≤0.5. CONCLUSIONS: The present results confirm that abatacept is effective and safe in routine clinical practice. It is possible that abatacept is more effective in seropositive RA patients with significant immunological abnormality. | |
27094943 | Calprotectin levels in patients with rheumatoid arthritis to assess and association with e | 2016 Nov | Rheumatoid arthritis (RA) is a chronic, inflammatory, and autoimmune disease that can cause permanent joint damage. In our study, we aim to analyze the change in calprotectin levels following the low-density exercise levels applied to the patients with RA. Twenty-eight patients with RA and 30 healthy controls were included in this study. To evaluate the activity of disease in RA, scores of disease activity that has increased (DAS-28) are figured. Calprotectin, nitric oxide (NO), white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) levels are tested as the laboratory evaluation. Calprotectin, NO, CRP, ESR, WBC, and RF levels were significantly higher in the patient group compared to the control group (p < 0.01, p < 0.001, p < 0.01, p < 0.01, p < 0.01, and p < 0.05, respectively). In correlation analysis applied to the patient group with RA, there has been determined a positive relation with calprotectin, and DAS-28, CRP, NO, RF, and WBC (p < 0.001, p < 0.05, p < 0.001, p < 0.05, and p < 0.05, respectively). In result of the low-density exercise treatment applied to patients with RA for 8 weeks, there has been determined a significant decrease in calprotectin, DAS-28, NO, CRP, ESR, and RF levels (p < 0.05, p < 0.001, p < 0.01, p < 0.05, p < 0.05, and p < 0.05, respectively). As a result, a significant relation is found between RA disease activity and calprotectin levels and other inflammatory parameters. At the same time, it shows that calprotectin which is a significant indicator of local inflammation can be used as a good identifier in following up exercise treatment. |