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

ID PMID Title PublicationDate abstract
27118031 The challenging interplay between rheumatoid arthritis, ageing and comorbidities. 2016 Apr 26 BACKGROUND: The incidence of rheumatoid arthritis (RA) is expected to increase over the next 10 years in the European Union because of the increasing proportion of elderly people. As both RA and ageing are associated with emerging comorbidities such as cardiovascular disease, malignancies and osteoporosis, these factors will have a profound effect on the management of RA. In addition, both increasing age and comorbidities may independently alter commonly used RA-specific outcome measures. DISCUSSION: Age-related decline in immune cell functions (immunosenescence), such as a decrease in T-cell function, may contribute to the development of RA, as well as comorbidity. The chronic immune stimulation that occurs in RA may also lead to premature ageing and comorbidity. The interplay between RA, ageing and (emerging) comorbidities is interesting but complex. Cardiovascular disease, lung disease, malignancies, bone and muscle wasting and neuropsychiatric disease all occur more frequently in RA patients as compared to the general population. It is unclear how RA should be managed in 'today's world of multiple comorbidities'. Evidence that treatment of RA improves comorbidities is currently lacking, although some promising indirect observations are available. On the other hand, there is limited evidence that medication regularly prescribed for comorbidities, such as statins, might improve RA disease activity. Both ageing and comorbidity have an independent effect on commonly used outcome measures in the RA field, such as the Health Assessment Questionnaire (HAQ) and the clinical disease activity index (CDAI). Prospective studies, that also account for the presence of comorbidity in (elderly) RA patients are therefore urgently needed. To address gaps in knowledge, future research should focus on the complex interdependencies between RA, ageing and comorbidity. In addition, these findings should be integrated into daily clinical practice by developing and testing integrated and coordinated health care services. Adaptation of management recommendations is likely required. The elderly RA patient who also deals with (emerging) comorbidities presents a unique challenge to treating clinicians. A paradigm shift from disease-centered to goal-oriented approach is needed to develop adequate health care services for these patients.
26457916 Glucocorticoids in the treatment of rheumatoid arthritis. 2015 Jul Glucocorticoids (GC) are now being used for over 65 years in the treatment of rheumatoid arthritis (RA). There is by now good evidence for their disease modifying effect, especially in early RA. When used in a dosage of 7.5-10 mg most adverse effects can be quite well handled, though monitoring and awareness for infections are important. The CAMERA II study is discussed, in which patients with early RA were treated with a tight control scheme of climbing dosages of methotrexate plus either 10 mg prednisone daily or placebo. After the two years of the trial, 70% of the patients treated with tight control strategy without GC had no erosions versus 82% of the patients treated with additional prednisone. Remission was reached more often and earlier on in the strategy with prednisone compared to the strategy with placebo. It may be suggested that GC have a greater beneficial effect on joint structure than can be explained by their anti-inflammatory effects only.
26184539 Cachexia and adiposity in rheumatoid arthritis. Relevance for disease management and clini 2016 Mar Altered body composition is a frequent finding in rheumatoid arthritis and is associated with the two major outcomes of the disease: disability and cardiovascular mortality. It is estimated that up to two thirds of patients may be affected by loss of lean mass, the so-called rheumatoid cachexia. Hence, body weight being equal, the relative amount of lean mass is lower and that of body fat is higher in rheumatoid arthritis patients vs. healthy controls. Both disease-related factors and other factors, like drug treatments, physical activity and nutrition contribute to modify body composition in rheumatoid arthritis. The effect of pharmacological treatments, and notably of anti-TNF drugs, on body composition is controversial. Conversely, training programs to stimulate muscle growth can restore lean mass and reduce adiposity. There is good evidence that amelioration of body composition ameliorates function and reduces disability. Currently, there is no evidence that interventions that modify body composition can reduce cardiovascular morbidity and mortality in rheumatoid arthritis.
26612244 Rheumatoid arthritis and work: The impact of rheumatoid arthritis on absenteeism and prese 2015 Jun For patients with rheumatoid arthritis (RA), being in paid work is very important, and it increases self-esteem and financial independence. Although the management of RA has changed in the last 15 years to early aggressive treatment and the introduction of biologic treatments, many patients still have to take sick leave or even stop working because of their RA (i.e., absenteeism). For those remaining in paid work, patients may experience problems due to RA resulting in productivity loss while at work (i.e., presenteeism). The costs attributed to absenteeism and presenteeism (i.e., indirect costs) have been estimated to be very high, and they even exceed direct costs. However, there is no consensus on how to calculate these costs. This manuscript examines the relationship between the use of biologic therapy and absenteeism, with a focus on sick leave, and on presenteeism, and it provides an overview of indirect costs of absenteeism and presenteeism in those treated with biologic therapies.
25096602 Strategies to predict rheumatoid arthritis development in at-risk populations. 2016 Jan The development of RA is conceived as a multiple hit process and the more hits that are acquired, the greater the risk of developing clinically apparent RA. Several at-risk phases have been described, including the presence of genetic and environmental factors, RA-related autoantibodies and biomarkers and symptoms. Intervention in these preclinical phases may be more effective compared with intervention in the clinical phase. One prerequisite for preventive strategies is the ability to estimate an individual's risk adequately. This review evaluates the ability to predict the risk of RA in the various preclinical stages. Present data suggest that a combination of genetic and environmental factors is helpful to identify persons at high risk of RA among first-degree relatives. Furthermore, a combination of symptoms, antibody characteristics and environmental factors has been shown to be relevant for risk prediction in seropositive arthralgia patients. Large prospective studies are needed to validate and improve risk prediction in preclinical disease stages.
27122657 Endothelial Dysfunction and Inflammation: Immunity in Rheumatoid Arthritis. 2016 Inflammation, as a feature of rheumatoid arthritis (RA), leads to the activation of endothelial cells (ECs). Activated ECs induce atherosclerosis through an increased expression of leukocyte adhesion molecules. Endothelial dysfunction (ED) is recognized as a failure of endothelial repair mechanisms. It is also an early preclinical marker of atherosclerosis and is commonly found in RA patients. RA is now established as an independent cardiovascular risk factor, while mechanistic determinants of ED in RA are still poorly understood. An expanding body of study has shown that EC at a site of RA is both active participant and regulator of inflammatory process. Over the last decade, a role for endothelial dysfunction in RA associated with cardiovascular disease (CVD) has been hypothesized. At the same time, several maintenance drugs targeting this phenomenon have been tested, which has promising results. Assessment of endothelial function may be a useful tool to identify and monitor RA patients.
27650675 Treating rheumatoid arthritis to target: physician and patient adherence issues in contemp 2017 Jun Development of the treat-to-target (T2T) strategy, the process whereby drug therapy is adjusted until the therapeutic goal is achieved, has revolutionized how rheumatoid arthritis (RA) patients are treated. With the advent of T2T, the management of RA is more effective than ever, with the possibility of remission and other favorable clinical and patient-reported outcomes. Effective implementation of a T2T strategy in routine clinical practice mainly depends on the long-term commitment of physician and patient to T2T treatment recommendations. However, as T2T is a complex process involving aggressive early management with several steps of therapy modifications requiring frequent close monitoring of disease activity and drug toxicities, it may be more liable to suboptimal adherence in real-life clinical practice. The aim of the review is to present key issues related to patient medication adherence and physician adherence to the current RA treatment recommendations and their importance in optimizing the outcome of treatment in RA treated according to T2T strategy.
27720800 Redox signaling in rheumatoid arthritis and the preventive role of polyphenols. 2016 Dec 1 Rheumatoid arthritis (RA) is an autoimmune, inflammatory joint disease whose exact cause is still not completely known. Reactive oxygen species (ROS) are believed to be involved in the pathogenesis of RA. ROS are produced mostly by the phagocytic cells during oxidative burst and oxidative phosphorylation. Lipids, proteins and nucleic acids get damaged by the overproduction of ROS. Damaging effects of ROS are taken care by the enzymatic and non-enzymatic defence system of the body. Overproduction or inadequate elimination of reactive species leading to oxidative stress has been positively correlated with the disease severity in RA patients. ROS activates signal transduction pathways involved in the inflammatory response in RA. Understanding the complex interplay between signaling pathways might be useful for the development of new and effective therapeutics for RA. In this review we discuss the involvement of reactive species in the pathogenesis of RA and their elimination by antioxidant defence system. Role of various antioxidants/polyphenols which looks quite promising in the treatment of RA have also been discussed.
27481831 Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental 2017 Feb OBJECTIVE: Current research in rheumatoid arthritis focuses on preclinical disease phases as it is hypothesised that early preclinical treatment might prevent progression to full-blown disease. Since performance of studies in prearthritis phases in humans is challenging, animal models offer an opportunity to evaluate preventive treatments. We performed a systematic literature review and summarised treatment effects during different stages of arthritis development in animal models. METHODS: Eight medical literature databases were systematically searched. Studies were selected if they reported effects of synthetic or biological disease-modifying antirheumatic drugs in animal models of arthritis (collagen-induced arthritis and adjuvant-induced arthritis) on arthritis severity, as measured with arthritis severity scores, paw swelling or paw volume. Quality was assessed using an 11-item checklist. Study characteristics were extracted and effect sizes obtained in high-quality studies were summarised in meta-analyses. Studies were categorised into three groups: prophylactic (prior to generation of autoantibody response), prearthritis (after induction of autoantibody response) and therapeutic intervention (after arthritis development). RESULTS: Out of 1415 screened articles, 22 studies (including n=712 animals) were eligible of good quality and included in meta-analyses. Prophylactic (16 experiments, n=312 animals) and prearthritis treatment (9 experiments, n=156 animals) both were associated with a reduction of arthritis severity (p<0.001 and p=0.005, respectively). Stratified analyses for different antirheumatic drugs initiated in the prearthritis phase suggested higher efficacy of methotrexate than of anti-tumour necrosis factor. CONCLUSIONS: Data of experimental studies in animal models of arthritis suggest that prophylactic and prearthritis treatment strategies are effective and hint at differences in efficacy between antirheumatic drugs.
27181236 [Altered composition of gut microbiota in rheumatoid arthritis patients]. 2016 Manifestation of rheumatoid arthritis (RA) can be attributed to both genetic and environmental factors. Some researchers have been focusing on intestinal microbiota which is thought to be one of the environmental factors that may enhance the development of RA. The advancement of culture-independent, high throughput microbial DNA sequencing had enabled us to understand the interplay between intestinal microbiota and host immune systems. In this study, we have reviewed the previous findings in animal and human studies with respect to the role of intestinal microbiota in RA. Mouse models of arthritis have demonstrated that gut microbiota plays a critical role in the disease development. K/BxN and IL-1 receptor-antagonist knock-out mice did not develop disease in germ free condition, however, colonization of particular intestinal bacteria was sufficient to induce arthritis. Moreover, the dysbiosis was observed in the human RA patients from United States, China and Finland. Thus, we believe that endeavors to improve the dysbiosis would serve as a novel therapeutic or preventive strategy in RA patients.
27976535 Patient goals in rheumatoid arthritis care: A systematic review and qualitative synthesis. 2017 Dec OBJECTIVE: During the clinical encounter, rheumatoid arthritis (RA) patient goals for care often go unexplored. The aim of the present systematic review was to identify needs, goals and expectations of RA patients in order better to guide systematic elicitation of patient goals in clinical encounters. METHODS: An academic librarian searched MEDLINE, PsychINFO and the Cochrane Library using a specialized algorithm developed to identify articles about patient goals for RA care. Investigators screened search results according to prespecified inclusion criteria and then reviewed included articles and synthesized the evidence qualitatively, utilizing an inductive approach. RESULTS: A total of 909 titles were retrieved in the literature search, of which 871 were excluded after a title/abstract screen. Of the remaining 38, 22 papers were included in the final review. Investigators identified four major themes in the literature: (a) the bodily experience of RA; (b) achieving normalcy and maintaining wellness; (c) social connectedness and support; and (d) interpersonal and healthcare system interactions. CONCLUSION: Patients' goals when receiving care for RA are multidimensional and span several facets of everyday life. Goals for RA care should be collaboratively developed between patients and providers, with particular attention to the patient's life context and priorities.
26457422 From genetics to functional insights into rheumatoid arthritis. 2015 Jul Autoimmune diseases are caused by multiple factors. Rheumatoid Arthritis (RA) is one of the most common human systemic autoimmune diseases with a prevalence of 0.5%-1% worldwide. It is characterised by inflammation of the synovial tissue and formation of rheumatoid pannus, which erodes adjacent cartilage and bone, causing subsequent joint destruction. RA is believed to result from a combination of genetic and environmental factors. In addition to the well characterised HLA locus, a number of susceptibility genes and loci have been identified by genome-wide association studies (GWAS). However, genetic information alone does not necessarily yield insight into the understanding of the pathogenesis of RA. We previously reported that Peptidylarginine deiminase type 4 (PADI4) is one such RA susceptibility gene. PADI4 catalyses the conversion of peptidylarginine into peptidylcitrulline, and citrulline-containing epitopes are the most specific targets of many RA-specific autoantibodies. We established that SNPs within the coding region of PADI4 are associated with the development of RA and that these RA-associated SNPs produce allelically imbalanced gene expression, which has pathological consequences. However, the individual effects of susceptibility genes are likely to be small, and it is the combination of alleles along with strong effects on the specific pathways affected by these susceptibility genes that are essential for the development of RA. To understand the role of genetics in the pathogenesis of RA, it is therefore important to understand the physiological significance of each susceptibility gene in relation to RA.
26769136 Old and new therapeutics for Rheumatoid Arthritis: in vivo models and drug development. 2016 Development of novel drugs for treatment of chronic inflammatory diseases is to a large extent dependent on the availability of good experimental in vivo models in order to perform preclinical tests of new drugs and for the identification of novel drug targets. Here, we review a number of existing rodent models for Rheumatoid Arthritis in the context of how these models have been utilized for developing established therapy in Rheumatoid Arthritis and, furthermore, the present use of animal models for studies of novel drug candidates. We have studied the literature in the field for the use of in vivo models during development of anti-rheumatic drugs; from Methotrexate to various antibody treatments, to novel drugs that are, or have recently been, in clinical trials. For novel drugs, we have explored websites for clinical trials. Although a single Rheumatoid Arthritis in vivo model cannot mirror the complexity of disease development, there exist a number of good animal models for Rheumatoid Arthritis, each defining some parts in disease development, which are useful for studies of drug response. We find that many of the established drugs were not tested in in vivo models before being used in the clinic, but rather animal models have been subsequently used to find mechanisms for efficacy. Finally, we report a number of novel drugs, tested in preclinical in vivo models, presently in clinical trials.
26607389 Successes and failures of chemokine-pathway targeting in rheumatoid arthritis. 2016 Jan Chemokines and chemokine receptors are involved in leukocyte recruitment and angiogenesis underlying the pathogenesis of rheumatoid arthritis (RA) and other inflammatory rheumatic diseases. Numerous chemokines, along with both conventional and atypical cell-surface chemokine receptors, are found in inflamed synovia. Preclinical studies carried out in animal models of arthritis involving agents targeting chemokines and chemokine receptors have yielded promising results. However, most human trials of treatment of RA with antibodies and synthetic compounds targeting chemokine signalling have failed to show clinical improvements. Chemokines can have overlapping actions, and their activities can be altered by chemical modification or proteolytic degradation. Effective targeting of chemokine pathways must take acount of these properties, and can also require high levels of receptor occupancy by therapeutic agents to prevent signalling. CCR1 is a promising target for chemokine-receptor blockade.
26307192 Multifaceted roles of adiponectin in rheumatoid arthritis. 2015 Oct Adiponectin is a circulating hormone with pleiotropic functions in lipid and glucose metabolism secreted by adipocytes. It plays a beneficial role in cardiovascular functions and metabolic complications. Recently, growing researches have elucidated that increased adiponectin plasma levels correlate with severity of rheumatoid arthritis (RA) and it is speculative that adiponectin may link to RA. The association of adiponectin with potential inflammatory functions in RA has raised significant interests in exploring this adipokine as a target for RA-diagnostic and therapeutic applications. Despite significant advances in understanding adiponectin functions and signaling mechanisms, its roles in RA remain multifaceted and subject to controversy. This review highlights the evidences linking adiponectin to either anti-inflammatory or pro-inflammatory action in RA. The results of this review may provide important insight into adiponectin in the development of RA.
26932399 The specialist physician's approach to rheumatoid arthritis in South Africa. 2016 Mar Rheumatoid arthritis (RA) is expected to increase in Africa and South Africa. Due to the low numbers of rheumatologists in South Africa, specialist physicians also have to care for patients with RA. Furthermore several new developments have taken place in recent years which improved the management and outcome of RA. Classification criteria were updated, assessment follow-up tools were refined and above all, several new biological disease-modifying anti-rheumatic drugs were developed. Therefore it is imperative for specialist physicians to update themselves with the newest developments in the management of RA. This article provides an overview of the newest developments in the management of RA in the South African context. This approach may well apply to countries with similar specialist to patient ratios and disease profiles.
26084368 Nanomedicine delivers promising treatments for rheumatoid arthritis. 2015 An increased understanding in the pathophysiology of chronic inflammatory diseases, such as rheumatoid arthritis, reveals that the diseased tissue and the increased presence of macrophages and other overexpressed molecules within the tissue can be exploited to enhance the delivery of nanomedicine. Nanomedicine can passively accumulate into chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or be surface conjugated with a ligand to actively bind to receptors overexpressed by cells within chronic inflammatory tissues, leading to increased efficacy and reduced systemic side-effects. This review highlights the research conducted over the past decade on using nanomedicine for potential treatment of rheumatoid arthritis and summarizes some of the major findings and promising opportunities on using nanomedicine to treat this prevalent and chronic disease.
26548003 [Update rheumatism focusing on rheumatoid arthritis]. 2015 Sep 1 Rheumatic diseases do not only represent a challenge in day to day clinical medicine but also during underwriting and claims handling in insurance medicine. New diagnostic laboratory tests and therapeutic options constantly improve diagnostic quality and treatment outcomes. Using rheumatoid arthritis (RA) as an example this article explains how this new aspects found their way into international diagnostic criteria and treatment guidelines. The introduction of diagnostic ACPAs (Anti-Citrullinated Protein Antibodies) and the therapeutic use of currently still relatively expensive biologicals have to be highlighted in this respect. Backed by modern therapeutic options recent RA morbidity figures of employed persons indicate a shift to less severe morbidity spectra. For individual case evaluation it is of importance to understand the most relevant aspects of such innovations for adequate and sound case assessment in underwriting and claims.
27267163 Genetic susceptibility to rheumatoid arthritis and its implications for novel drug discove 2016 Aug INTRODUCTION: Over 100 susceptibility loci have now been identified for rheumatoid arthritis (RA), several of which are already the targets of approved RA therapies providing proof of concept for the use of genetics in novel drug development for RA. Determining how these loci contribute to disease will be key to elucidating the mechanisms driving disease development, which has the potential for major impact on therapeutic development. AREAS COVERED: Here the authors review the use of genetics in drug discovery, including the use of 'omics' data to prioritise potential drug targets at susceptibility loci using RA as an exemplar. They discuss the current state of RA genetics its impact on stratified medicine, and how the findings from RA genetics studies can be used to inform drug discovery. EXPERT OPINION: It is anticipated that functional characterisation of disease variants will provide biological validation of a gene as a drug target, providing safer targets, with an increased likelihood of efficacy. In the future, techniques such as genome editing may represent a plausible option for RA therapy. Technologies such as genome-wide chromatin conformation capture Hi-C and CRISPR will be crucial to inform our understanding of how diseases develop and in developing new treatments.
27716458 One year in review 2016: pathogenesis of rheumatoid arthritis. 2016 Sep Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic synovial inflammation leading to joint destruction and bone erosions. Although the pathogenic mechanisms underlying the disease are not fully elucidated, it is known that genetic susceptibility and environmental factors trigger an abnormal autoimmune response. Potentially, any organ and tissue could be affected by RA and the increased cardiovascular (CV) risk represents the major complication responsible for a worse prognosis. In this setting, the shared pathogenic mechanisms between RA pathogenesis and accelerated atherosclerosis further strengthen the rationale for a treat-to-target strategy with synthetic and biologic disease modifying anti-rheumatic drugs. The aim of this review is to provide the novel insights, regarding the pathogenesis of RA, published over the last year.