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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| 30047807 | New strategies for patenting biological medicines used in rheumatoid arthritis treatment. | 2018 Aug | INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by an inflammatory process, with a global prevalence ranging from 0.3% to 1%. The overall cost of RA drugs is estimated in $20 billion worldwide and projected to grow to $36 billion by 2021. The current RA treatment strategy consists of the aggressive therapy directed to specific targets, after diagnostic confirmation and the stepped therapy directed by the stage of the disease, aiming at the clinical remission. Conventional (methotrexate, sulfasalazine, leflunomide) and biological (infliximab, adalimumab, tocilizumab) disease-modifying antirheumatic drugs may fail, produce only partial responses, or unwanted side effects, and consequently new antirheumatic drugs are being developed to overcome these limitations. AREAS COVERED: In this review, the authors described the technological trends and the main players involved in the R&D process related to biological compounds employed in the treatment of RA, using patent documents as a source of technological information. EXPERT OPINION: Current treatments for RA still mainly target the immune system, different inflammatory targets, and mediators. Other types of therapies have also been developed, such as vaccines and gene therapies. Despite these new techniques, the main compounds of interest remain the antibodies anti-TNF-α and anti-CD20, with novelties regarding preparation methods and combination targets. | |
| 29390903 | Juggling identities of rheumatoid arthritis, motherhood and paid work - a grounded theory | 2019 Jun | PURPOSE: To explore how women with rheumatoid arthritis manage their illness, motherhood, and work life. METHODS: A constructivist, grounded theory approach based on individual interviews and participant observations with 20 women with rheumatoid arthritis who participated in work life and had children living at home or were pregnant. After initial and focused coding Goffman's concepts of social identity were applied. RESULTS: A core category: "Juggling meaningful identities" and three conceptual categories were developed: (1) Work life as the strongest identity marker; (2) Motherhood: a two-sided act; (3) Living with rheumatoid arthritis as an identity? Paid work, motherhood, and illness are linked to the women's social identities. The women construct and change their identities in interactions with children, partners, other parents, colleagues, and employers. CONCLUSION: The women attribute the highest priority to their professional identity, spending the majority of their time and energy in an effort to appear as "good stable workers". The disease is seen as a hindrance in this regard, and the illness identity is almost completely rejected. In motherhood, the women prioritize close interaction with their children, and deprioritize external activities. Extended outbreaks of the disease and issues regarding the children force the women to deprioritize working life. Implications for rehabilitation Juggling meaningful identities of rheumatoid arthritis, motherhood, and paid work challenge women in managing their everyday lives. Therefore, rehabilitation professionals should support individuals to develop new strategies to manage the challenges they experience regarding juggling motherhood and work ability. Work is a dominant identity marker for women with rheumatoid arthritis therefore, rehabilitation professionals have an important role to play in investigating possible ways for the individual to maintain employment or return to work. Living with rheumatoid arthritis and being a paid worker challenge women's role performance and thereby their identification as mothers. Therefore, rehabilitation professionals have to support the women and their families. | |
| 29709290 | The use of routinely collected patient-reported outcome measures in rheumatoid arthritis. | 2018 Dec | This study systematically reviewed commonly used patient-reported outcome measures (PROMs) for rheumatoid arthritis (RA), routinely collected in clinical practice, and evaluated objectives of their use. An additional survey conducted among identified RA registries provided additional information about collection of PROMs. Medline Ovid and Embase were searched for observational studies using data of RA registries/cohorts, published between 2011 and 2016. The search combined a validated search algorithm for PROMs and RA. Study characteristics, objective, registry, country, type of PROMs collected, and time interval of collection were systematically recorded. The survey asked about PROMs collected by the registries, timing, response rates, and barriers to collection. Ninety-eight articles from 15 countries were identified making use of 37 registries and large cohorts. Thirty-three PROMs were collected routinely, with VAS, EQ-5d and HAQ being the most used tools. Health domains reported the most were functional assessment, pain and patient global assessment. Despite the wide variety of collected PROMs, foci of the articles were similar and reported results narrow. This review suggests rethinking the role of PROMs in rheumatology research to use this information as broadly as possible, including evaluation of treatments, economic analyses, and decision-making based on patients' experiences at system, provider, and physician level. | |
| 28758827 | Lymphoproliferative disorders in patients with rheumatoid arthritis in the era of widespre | 2018 Jan | Lymphoproliferative disorders (LPD) in patients receiving methotrexate (MTX) have gained strong attention. In this article, I reviewed the basic and clinical findings of this issue. Patients with RA possess a high risk of lymphoma, but epidemiological evidence showing an association between the use of MTX and lymphoma is still limited. Rapid regression of LPD after stopping MTX in patients with RA strongly suggests that there is a causative relationship. Genetic predisposition, accumulated inflammation, impaired generation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes, effects of MTX on the regulation of EBV genes, and low hypermethylation of apoptosis-related genes are relevant to the development of LPD and rapid regression after cessation of MTX. The clinical and histological characteristics of LPD in RA patients who are treated with MTX have been established, and recent data indicate that initial cessation of MTX and watchful waiting to observe an increase in peripheral lymphocyte counts have a therapeutic value. In advanced cases, various chemotherapy regimens are used, and consultation with hematologists is recommended to select the optimal treatment. There is no consensus on the treatment of RA after development of LPD, and long-term observation is necessary to investigate the safety of disease-modifying antirheumatic drugs in these patients. | |
| 29704191 | Morning Stiffness in Elderly Patients with Rheumatoid Arthritis: What is Known About the E | 2018 Jun | Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects all age groups, but the prevalence appears to increase with age. Elderly-onset RA (after the age of 60Â years) has distinct clinical patterns. Treatment of RA in older individuals is confounded by the presence of medical comorbidities, concurrent medications, drug interactions, and the altered pharmacokinetics and pharmacodynamics related to aging and organ dysfunction. Patients with RA commonly experience morning stiffness, which is associated with reduced quality of life and work disability. However, despite its importance, morning stiffness is seldom assessed in clinical practice and usually only its duration is measured in the research setting. Whether the intensity, timing, location and impact of this symptom should be assessed in future clinical trials requires further evaluation. The biologic and newer targeted synthetic disease-modifying anti-rheumatic drugs have been shown to be effective in reducing the duration of morning stiffness in patients with RA. Glucocorticoids are a double-edged sword in RA. Although they can effectively reduce inflammation and retard radiological damage (disease modifying), the long-term use of glucocorticoids is associated with numerous adverse effects. Thus, glucocorticoids should be used for short-term treatment of RA only. Night-time administration of glucocorticoids has been shown to alleviate morning stiffness and should be considered in patients with serious morning joint stiffness symptoms. | |
| 30687310 | Clinical Relevance of Galectin-1 and Galectin-3 in Rheumatoid Arthritis Patients: Differen | 2018 | Galectins, a family of animal lectins, play central roles in immune system regulation, shaping both innate and adaptive responses in physiological and pathological processes. These include rheumatoid arthritis (RA), a chronic multifactorial autoimmune disease characterized by inflammatory responses that affects both articular and extra-articular tissues. Galectins have been reported to play central roles in RA and its experimental animal models. In this perspective article we present new data highlighting the regulated expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) in sera from RA patients under disease-modifying anti-rheumatic drugs (DMARDs) and/or corticoid treatment in the context of a more comprehensive discussion that summarizes the roles of galectins in joint inflammation. We found that Gal-1 levels markedly increase in sera from RA patients and positively correlate with erythrocyte sedimentation rate (ERS) and disease activity score 28 (DAS-28) parameters. On the other hand, Gal-3 is downregulated in RA patients, but positively correlates with health assessment questionnaire parameter (HAQ). Finally, by generating receiver-operator characteristic (ROC) curves, we found that Gal-1 and Gal-3 serum levels constitute good parameters to discriminate patients with RA from healthy individuals. Our findings uncover a differential regulation of Gal-1 and Gal-3 which might contribute to the anti-inflammatory effects elicited by DMARDs and corticoid treatment in RA patients. | |
| 30221835 | Move to Nano-Arthrology: Targeted Stimuli-Responsive Nanomedicines Combat Adaptive Treatme | 2019 Jan | Rheumatoid arthritis (RA) is one of the most popular chronic autoimmune diseases characterized with persistent synovial inflammation and bone destruction. Although considerable developments have been gained in clinical treatment of RA, the major drawback to RA therapy stems from the adaptive treatment tolerance (ATT) following the long-term drug use, which causes compromised efficacy, sustained drug dose increase, and severe adverse events. To address these challenges, it is of great significance to put forward innovative therapeutic approaches for RA treatment. Nowadays, developments of nanotechnology-based nanomedicines (NMs) for RA are in progress. Multifunctional NMs with targeted stimuli-responsive features have been one of the central concepts in designing more accessible formulations for efficient RA treatment. These NMs are able to postpone RA progression effectively, because of their delivery and on-demand release of medicaments at targeted sites in response to external or internal stimuli related to the RA pathophysiology without obvious adverse side-effects on the normal tissues. Therefore, NMs have gained interest from pre-clinical research scientists as well as clinical doctors worldwide. Herein, the authors highlight the recent attempts of targeted stimuli-responsive NMs for RA therapy in the last 5 years. The described progresses may pave the way to novel and highly effective RA NMs. | |
| 29556705 | The effectiveness of therapeutic shoes in patients with rheumatoid arthritis: a systematic | 2018 May | The study summarizes the evidence on the effectiveness of therapeutic shoes on foot function, foot pain, physical functioning, health-related quality of life, adherence, adverse events and patient satisfaction in patients with rheumatoid arthritis (RA). Studies investigating the effect of (ready- or custom-made) therapeutic shoes were included. For between-group designs, studies comparing therapeutic shoes versus non-therapeutic shoes were included. A literature search was conducted in The Cochrane Central Registry for Controlled Trials (CENTRAL), PubMed, EMBASE and PEDro up to January 19, 2017. Quantitative data analysis was conducted; when this was not possible qualitative data analysis was performed. Eleven studies were identified. For custom-made shoes, no studies reporting between-group differences were available. Qualitative data-syntheses of the within-group differences resulted in weak evidence for the reduction of foot pain and improvement of physical functioning. For ready-made shoes, one study reported between-group differences, resulting in inconclusive evidence for improvement of foot function. Quantitative data-analyses of within-group differences resulted in a medium to large effect for the reduction of foot pain (SMD 0.60, 95% CI 0.28-0.92; P ≤ 0.001; 184 participants) and a small to medium effect for the improvement of physical functioning (SMD 0.30, 95% CI 0.04-0.56; P = 0.02; 150 participants). Qualitative data-synthesis of within-group differences resulted in weak evidence for improvement of foot function. Within-group results indicate that therapeutic shoes are likely to be effective in patients with RA. Definitive high-quality RCTs are necessary to investigate the between-group effectiveness of therapeutic shoes in patients with RA. | |
| 29702364 | Mechanisms and therapeutic targets for bone damage in rheumatoid arthritis, in particular | 2018 Jun | Rheumatoid arthritis (RA), a chronic inflammatory disorder, causes swelling, bone erosion, and joint deformity. Bone erosion in RA-affected joints arises from activation of osteoclasts by inflammatory processes. RA patients may also have primary, disease-related, or glucocorticoid-induced osteoporosis, caused by a disrupted balance between osteoclasts and osteoblasts. Disease-modifying antirheumatic drugs (DMARDs) interfere with the processes causing inflammation in the joint but do not sufficiently treat bone erosion and osteoporosis. Denosumab, an inhibitor of receptor activator of nuclear factor κ-B ligand (RANKL), protects bones in osteoporosis patients. Clinical studies have demonstrated that denosumab can also prevent bone erosion in RA patients. Because joint destruction progresses in some patients treated with DMARDs alone, denosumab will likely become standard treatment for some RA patients. | |
| 28768630 | Back to the future: forget ultrasound and focus on clinical assessment in rheumatoid arthr | 2018 Jan | Ultrasound (US) unquestionably improves many aspects of rheumatoid arthritis (RA) diagnosis and management, but no consensus has been reached regarding the optimal US methodology that should be used, and high levels of standardisation have not yet been attained. Current evidence from two randomised controlled trials does not support the US in directing treatment decisions. A return to the endorsement of clinical assessment and the adoption of T2T strategies aiming at ACR/EULAR remission still represent the standard of care for RA and should be pursued through appropriate educational programmes. Thus, for now, the major application of sonography in arthritis should have a focus on diagnostic and especially differential diagnostic aspects. | |
| 29693487 | The potential impact of monitoring disease activity biomarkers on rheumatoid arthritis out | 2018 Jul 1 | Rheumatoid arthritis (RA) management requires monitoring of disease activity to determine course of treatment. Global assessments are used in clinical practice to determine RA disease activity. Monitoring disease activity via biomarkers may also help providers optimize biologic and nonbiologic drug use while decreasing overall drug spend by delaying use of expensive biologic therapies. By testing multiple biologic domains at the same time, a multibiomarker disease activity test may have utility in RA patient management, through improved intra- and inter-rater reliability. This report provides a comprehensive review of studies of objective measures, single biomarkers and multibiomarker disease activity tests as disease activity measures to decrease uncertainty in treatment decisions, and of biomarkers' potential impact on economic and clinical outcomes of treatment choices. | |
| 29691690 | [Biomarkers and imaging for diagnosis and stratification of rheumatoid arthritis and spond | 2018 May | Rheumatic diseases are among the most common chronic inflammatory disorders. Besides severe pain and progressive destruction of the joints, rheumatoid arthritis (RA), spondyloarthritides (SpA) and psoriatic arthritis (PsA) impair working ability, reduce quality of life and if treated insufficiently may enhance mortality. With the introduction of biologics to treat these diseases, the demand for biomarkers of early diagnosis and therapeutic stratification has been growing continuously. The main goal of the consortium ArthroMark is to identify new biomarkers and to apply modern imaging technologies for diagnosis, follow-up assessment and stratification of patients with RA, SpA and PsA. With the development of new biomarkers for these diseases, the ArthroMark project contributes to research in chronic diseases of the musculoskeletal system. The cooperation between different national centers will utilize site-specific resources, such as biobanks and clinical studies for sharing and gainful networking of individual core areas in biomarker analysis. Joint data management and harmonization of data assessment as well as best practice characterization of patients with new imaging technologies will optimize quality of marker validation. | |
| 29103073 | The Efficacy of Tai Chi and Yoga in Rheumatoid Arthritis and Spondyloarthropathies: A narr | 2018 Mar | Rheumatoid arthritis (RA) and spondyloarthropathies (SpA) are among the most common inflammatory rheumatic diseases, which might induce chronic pain for their sufferers. Mind-body interventions like Tai Chi and yoga are among the many alternative therapies for combatting chronic pain. This review aims to overview the articles about their effectiveness in RA and SpA. We searched PubMed/MEDLINE, Scopus, and Web of Science for English-language sources from their inception through September 2017. Case-control studies, interventional studies, and case series that included more than three cases and randomized crossover studies were included. The literature search retrieved 133 non-duplicate records, and 15 of them were eligible and were included in this review. The influence of Tai Chi remains debatable in RA, while there is only one study that investigated its efficacy in SpA. Yoga seems effective in decreasing pain and inflammation while increasing quality of life. There are no data available about its effect on SpA. Even after a thorough research, the number of articles is quite limited on the effectiveness of Tai Chi and yoga in RA and SpA. While these complementary approaches still show some promise as alternative therapies in RA and SpA, the literature lacks long-term studies with larger patient groups. | |
| 29473438 | CRISPR and personalized Treg therapy: new insights into the treatment of rheumatoid arthri | 2018 Jun | INTRODUCTION: Rheumatoid arthritis (RA), as one of the most disabling autoimmune diseases, is a common health problem that progressively reduces the life quality of patients. Although various biologics have been introduced for RA, attempts to establish an efficient long-term therapies failed due to the heterogeneity of this disease. METHODS: In the last decade, immunomodulatory approaches such as T cell adoptive therapy have been developed for controlling autoimmunity. Regulatory T cells (Tregs), the major self-tolerance mediator, are crucial for down-regulation of aberrant immune stimulations. Hence, recruiting ex vivo Tregs emerged as a promising therapy for a variety of autoimmune diseases. RESULTS: The major bottleneck of the Treg adoptive therapy is maintaining the in vivo stability and plasticity of these fascinating cells. Recent progress in genome editing technology clustered regularly interspaced short palindromic repeats (CRISPR) in combination with CRISPR-associated (Cas) 9 system provided a new solution for this bottleneck. CONCLUSIONS: The present paper discusses RA pathogenesis and the potential application of new developments in CRISPR-mediated Treg genome editing in personalized therapy of RA. | |
| 30296973 | Imaging detected tenosynovitis of metacarpophalangeal and wrist joints: an increasingly re | 2018 Sep | Tenosynovitis is traditionally recognised at physical examination in patients with inflammatory rheumatic diseases, such as, e.g. psoriatic arthritis and (longstanding) rheumatoid arthritis (RA). The increasing use of sensitive imaging techniques (ultrasound, magnetic resonance imaging (MRI)) has recently revealed that subclinical tenosynovitis is prevalent in early RA and in patients in different phases of RA development (asymptomatic state, arthralgia, early arthritis). In this review, the recent findings on MRI-detected tenosynovitis and associations with RA development are highlighted, and an overview of the most reported inflamed tendon locations within the hand and wrist of patients in different disease phases is provided. The data presented show that tenosynovitis is one of the earliest inflammatory features in patients with imminent RA and associated with impairment of activities in daily life. The value of tenosynovitis as an outcome measure in RA is also discussed. | |
| 29164267 | Intracellular apoptotic pathways: a potential target for reducing joint damage in rheumato | 2018 Mar | Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that results in both local and systemic bone erosion, causing significant joint deformities and functional disability. The increased number of synovial fibroblasts, inflammatory cells and osteoclasts in RA is associated with reduced apoptosis in these cells. The ability to modulate the cell proliferation or death (particularly apoptosis) is recognised for its immense therapeutic potential. Identifying new therapeutics to assist in stimulating apoptosis within the synovial joints therefore may be beneficial in reducing inflammation and bone loss in RA patients. In this review, the roles of anti-apoptotic proteins that are upregulated in RA synovial joints will be discussed in relation to their actions on bone destruction and inflammation. Evidence recently published suggests that intracellular apoptotic inhibitory molecules can be targeted by current or new therapeutics to reduce joint damage in RA. However, the therapeutics that target these molecules are yet to reach clinical trial stages. Even so it is evident that understanding the upregulation of anti-apoptotic molecules in RA is required to improve treatments currently available for RA patients. | |
| 30062629 | Influence of disease-modifying antirheumatic drugs on oxidative and nitrosative stress in | 2018 Oct | BACKGROUND: Nitro-oxidative stress plays a central role in the pathogenesis of rheumatoid arthritis (RA) and several articles show correlation with disease activity. However, the influence and mechanisms by which disease-modifying antirheumatic drugs (DMARDs) may interfere with nitro-oxidative stress are poorly understood. OBJECTIVE: To show the available data on the effect of the DMARDs on the nitro-oxidative stress in RA patients. METHODS: A bibliographic search was carried out in the electronic databases PUBMED, Lilacs, Scientific Electronic Library Online (SCIELO), and Science Direct and the research was limited to human studies, independently of the publication date. RESULTS: Most studies were performed with infliximab (IFX, 4 articles), tocilizumab (TCZ, 3 articles) and methotrexate (MTX, 2 articles). MTX and leflunomide showed similar results with reduction of nitric oxide. The studies with TCZ verified a marked decrease of reactive oxygen and nitrogen species. Most studies with IFX found a reduction of protein oxidation, evaluated by protein carbonyl measurement. In the present review, the most remarkable results were observed with the increase of the antioxidant defenses through several markers and antioxidant systems. The only study with etanercept showed very similar results to those obtained with MTX, with decreased pentosidine and oxidative DNA damage. CONCLUSIONS: The majority of the studies reported in this work showed an improvement in the redox state, which could be related to success of the therapy. Thus, oxidative and nitrosative stress markers may be useful to early evaluate the response of DMARDs in patients with RA. | |
| 30297575 | Benefits of anticitrullinated peptides examination in rheumatoid arthritis. | 2018 Oct | BACKGROUND: Anti-citrullinated peptides antibodies (ACPA) are specific for rheumatoid arthritis and have been implicated in disease pathogenesis. ACPA examination is a new component of ACR/EULAR 2010 classification criteria for rheumatoid arthritis. ACPA positivity predicts a more erosive disease course with severe joint damage and extra-articular manifestations. OBJECTIVES: To evaluate the benefits of ACPA examination in patients with early undifferentiated arthritis and patients with rheumatoid arthritis. METHODS: We examined patients with arthritis and tested them for ACPA positivity. In every individual patient we evaluated if ACPA examination was necessary to establish the diagnosis of rheumatoid arthritis, or to change treatment, or if the diagnosis could have been established without ACPA examination (ACR/EULAR 2010 classification criteria was met without ACPA scoring). RESULTS AND CONCLUSIONS: The study was placed in Slovak Republic. We examined 833 patients with arthritis. There were 43 patients, or 62% of a subgroup of 69 who were ACPA positive whose ACPA examination was not needed-ACR/EULAR criteria was met without ACPA scoring. This number represents 5.1% of the total number examined. There were 15 patients, or 22% of the subgroup and 1.8% of the total whose diagnosis was revised to rheumatoid arthritis due to ACPA positivity-ACR/EULAR criteria were met solely with ACPA scoring. There were 11 patients (16% and 1.3%) whose medication was changed due to ACPA positivity. ACPA examination is useful in 3.1% of all examined patients. When we correlate data on ACPA positive patients, 38% of the patients profit from ACPA examinations. Considering the relatively low price of ACPA testing, this examination should not be excluded. | |
| 30166712 | PATHOGENESIS OF RHEUMATOID ARTHRITIS: THE INTERSECTION OF GENETICS AND EPIGENETICS. | 2018 | Rheumatoid arthritis is a synovial inflammatory disease marked by joint infiltration by immune cells and damage to the extracellular matrix. Although genetics plays a critical role in heritability and its pathogenesis, the relative lack of disease concordance in identical twins suggests that noncoding influences can affect risk and severity. Environmental stress, which can be reflected in the genome as altered epigenetic marks, also contributes to gene regulation and contributes to disease mechanisms. Studies on DNA methylation suggest that synovial cells, most notably fibroblast-like synoviocytes, are imprinted in rheumatoid arthritis with epigenetic marks and subsequently assume an aggressive phenotype. Even more interesting, the synoviocyte marks are not only disease specific but can vary depending on the joint of origin. Understanding the epigenetic landscape using unbiased methods can potentially identify nonobvious pathways and genes that that are responsible for synovial inflammation as well as the diversity of responses to targeted agents. The information can also be leveraged to identify novel therapeutic approaches. | |
| 29496225 | Do out-of-pocket costs affect medication adherence in adults with rheumatoid arthritis? A | 2018 Aug | INTRODUCTION: For individuals with a chronic condition, long-term management of their medication can be difficult and as a result non-adherence is common among this cohort. In patients with rheumatoid arthritis (RA), the introduction of biologic agents was a revolutionary treatment but the high costs of this medication might limit their utilisation. OBJECTIVE: This systematic review aimed to determine whether out-of-pocket (OOP) costs affect adherence to RA medications in adults with a diagnosis of RA. METHODS: Twelve databases were searched to identify primary peer-reviewed articles, written in English from inception to April 2016 that referred to the relationship between adherence to RA medication and OOP costs. The CASP check list was used to assess the quality rating of the included studies. RESULTS: Six articles were identified in the review and all were considered as high quality studies. Among them, three directly considered the association between OOP costs and medication adherence as their main objective. Although the population and the methods of the studies varied widely, there was an inverse relationship between OOP costs and medication adherence in patients with RA. CONCLUSION: The findings of this review suggest that OOP costs can contribute to non-adherence to RA medication in patients with RA. Therefore, health policy makers globally should identify the appropriate OOP amount so these costs do not affect adherence whilst simultaneously ensuring that costs are not an intolerable burden for governments, providers and insurers. |