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ID PMID Title PublicationDate abstract
32143989 Insights into the treatment of rheumatoid arthritis: A paradigm in medicine. 2020 Jun Insights into rheumatoid arthritis (RA) have slowly evolved over the last century, but with breathtaking speed over the last 2 decades. While only aspirin and parenteral gold were available in early 20th century, the efficacy of sulfasalazine, glucocorticoids and methotrexate was established around its middle. Identification of pathogenetic pathways was slow, and until today the role of T-cells is enigmatic, while it is clear that genetics via the shared epitope and other genes as well as environmental factors including the metagenome play major roles. More clarity evolved on importance of proinflammatory cytokines, especially TNF and IL-6. The activation of osteoclasts, the culprits of bony joint damage, is amplified by the proinflammatory cytokines. The realization of TNF's central role led to the successful introduction of TNF-inhibitors and subsequently also inhibitors of other cytokines and cells as well as signal transduction. In parallel, the evolution of outcomes research has contributed importantly to RA management. At the turn to the 21st century, improvement criteria and continuous indices were created, allowing reliable therapeutic response determination, including definition of endpoints like remission. Also our understanding of the role of disease activity relative to disease pathology has increased, ultimately fostering the treat-to-target concept and recommendations and, thus, optimal outcomes for RA patients as never been seen before. Similar developments are now ultimately being introduced in the field of psoriatic arthritis. Here many of these aspects are reviewed from a very personal perspective of the author in the hopes of further helping parients with chronic forms of arthritis.
32954452 Focus on the Multimodal Role of Autophagy in Rheumatoid Arthritis. 2021 Feb Autophagy exerts its dual role in eukaryotic cells and exerts its cytoprotective action through degradation mechanism and by regulating catabolic processes which results in elimination of pathogens. Under suitable conditions, autophagy is associated with recycling of cytoplasmic components which causes regeneration of energy whereas deregulated autophagy exerts its implicated role in development and pathogenesis of auto-immune diseases such as rheumatoid arthritis. The immune, innate, and adaptive responses are regulated through the development, proliferation, and growth of lymphocytes. Such innate and adaptive responses can act as mediator of arthritis; along with this, stimulation of osteoclast-mediated bone resorption takes place via transferring citrullinated peptides towards MHC (major histocompatibility complex) compartments, thereby resulting in degradation of bone. Processes such as apoptosis resistance are also regulated through autophagy. In this review, the current knowledge based on role of autophagy in pathogenesis of rheumatoid arthritis is summarized along with proteins associated.
33584645 Neutrophil Extracellular Traps Tied to Rheumatoid Arthritis: Points to Ponder. 2020 In recent years, neutrophil extracellular traps at the forefront of neutrophil biology have proven to help capture and kill pathogens involved in the inflammatory process. There is growing evidence that persistent neutrophil extracellular traps drive the pathogenesis of autoimmune diseases. In this paper, we summarize the potential of neutrophil extracellular traps to drive the pathogenesis of rheumatoid arthritis and experimental animal models. We also describe the diagnosis and treatment of rheumatoid arthritis in association with neutrophil extracellular traps.
32388745 When rheumatoid arthritis is mentioned, should only dryness come to mind? 2020 Nov OBJECTIVE: To evaluate corneal parameters of rheumatoid arthritis (RA) patients by corneal topography. METHODS: One hundred two RA patients and 60 control subjects were enrolled. Corneal topography measurements and ophthalmologic findings were examined from all participants' files. RESULTS: Corneal thickness measurements were significantly lower in the RA group (p = 0.025). All values of corneal curvatures (K1, K2, Kmean) in 3 mm, 5 mm, and 7 mm zones were found statistically significantly higher in the RA group compared with the control group. Forty-five RA patients had a dry eye. Disease duration was correlated with dry eye in the RA group. There was a significant correlation between the duration of disease in RA patients and mean corneal curvatures (p 0.012/0.010/0.007, 3/5/7 mm respectively) and central corneal thickness (p 0.025). There is no statistical difference between other topographic measurements. CONCLUSIONS: The results suggest that RA patients have thinner and steeper corneas compared with control subjects. These parameters change in negative correlation as the duration of the disease increases. Key Points • Rheumatoid arthritis is an autoimmune disease with systemic involvement. • In rheumatoid arthritis, systemic involvement is affected in the eyes. • When it comes to eye involvement, it comes to mind that it makes the eyes more dryness. • In addition to dryness in the eyes, rheumatoid arthritis makes morphological changes in the cornea.
32981645 Disparities in Rheumatoid Arthritis Care and Health Service Solutions to Equity. 2020 Nov Proximal, intermediate, and distal social determinants of health inform the health of populations. Differences in rheumatoid arthritis outcomes between populations reflect inequities in these determinants. However, health service access, medication availability, and high-quality care interactions can be ensured through health system restructuring and innovations in individual-level care provision. This article summarizes disparities in rheumatoid arthritis care that have been recognized and described in the United States and Canada and proposes models of care and treatment approaches that can support better outcomes for population groups at risk for outcome inequities.
33199321 Rheumatoid arthritis and bone health. 2020 Nov Rheumatoid arthritis (RA) is an inflammatory arthropathy affecting 1% of the population, with a female predominance. Systemic inflammation is a key component of RA disease; corticosteroids are often required to rapidly control disease activity. Both inflammation and corticosteroids, however, have an adverse effect on bone mineral density, potentially resulting in osteoporosis and an increased risk of fractures. In this article, we describe the link between RA and impaired bone health, together with appropriate strategies to maintain bone density and reduce fracture risk. Key approaches include achieving adequate control of inflammation, minimising corticosteroid use, monitoring bone mineral density and intervening with antiosteoporosis medications when indicated.
32245893 Economic burden of rheumatoid arthritis: a systematic review of literature in biologic era 2020 Jun BACKGROUND: The past decades have seen rapid advances in the treatment of rheumatoid arthritis (RA). In particular, the introduction of biologic and targeted synthetic disease-modifying antirheumatic drugs have improved clinical outcomes and reconfigured traditional RA cost compositions. OBJECTIVES: To map the existing evidence concerning cost of illness of RA, as the treatment pathway evolves in the biologic era, and examine how costs have been measured and estimated, in order to assemble and appropriately interpret available data. METHODS: Systematic review of studies that estimated the costs of patients with RA. Multiple electronic databases were searched to identify studies published between 2000 and 2019. The reported total costs and cost components were evaluated according to the study and population characteristics. The Cochran-Armitage test was used to determine statistically significant trends in increasing or decreasing proportions over time. RESULTS: Overall, 72 studies were included. Drug costs compromised the main component (up to 87%) of direct costs with an increasing trajectory over time, although not statistically significant. The proportion of costs for hospitalisation showed a statistically significant decrease chronologically (p=0.044). Indirect costs, primarily associated with absenteeism and work disability accounted for 39% to 86% of total costs. The reported indirect costs are highly sensitive to the approach to estimation. CONCLUSIONS: A decreasing trend in inpatient costs chronologically suggested a cost shift in other components of direct costs. Indirect costs still contributed a considerable proportion of total costs, with work disability being the main cost component. Economic analyses that do not incorporate or appropriately measure indirect costs will underestimate the full economic impact of RA.
32030763 Lung inflammation in the pathogenesis of rheumatoid arthritis. 2020 Mar The primary manifestation of rheumatoid arthritis (RA) is articular disease; however, extra-articular disease can also occur. In particular, pulmonary disease is a leading cause of morbidity and mortality in individuals with RA. Herein, we will review the types, prevalence, risk factors, and potential pathophysiology of lung disease in individuals with established RA. We will also discuss the emerging understanding of potential role of the lung in the generation of RA-related autoantibodies during a period of disease development termed "pre-RA." Finally, we will discuss a research agenda outlining the next steps to improve our understanding and management of lung inflammation and lung disease throughout the natural history of RA.
32100561 Molecular mechanisms underlying rheumatoid arthritis and cancer development and treatment. 2020 Mar Given recent advances in cancer immune therapy, specifically use of checkpoint inhibitors, understanding the link between autoimmunity and cancer is essential. Rheumatoid arthritis (RA) affects about 1% of the population, and early diagnosis is key to prevent joint damage. Management consists of disease-modifying antirheumatic drugs that alter normal immunologic pathways, which could affect malignancy growth and survival. Prolonged immune dysregulation and the resulting inflammatory response associated with development of RA may also lead to increased cancer development risk. RA has long been associated with increased risk of non-Hodgkin's lymphoma [1] and further evidence supports relationship to lung cancer [2]. This review will address the mechanisms behind cancer development and progression in RA patients, biomarkers and assess cancer risk and early detection.
32351318 Synovial Macrophages in Rheumatoid Arthritis: The Past, Present, and Future. 2020 The ontogeny of macrophages in most organs has already been established. Owing to the limited number and inaccessibility of synovial macrophages (SMs), the origin of SMs has not been fully elucidated. Previous studies suggested that SMs have two major origins, namely, tissue-resident and monocyte-derived SMs. However, no systematic analysis to identify SM ontology in either physiological or pathological conditions has been available to date. In this review, we summarize relevant studies on the two main origins of SMs in rheumatoid arthritis (RA) and forecast the future research directions for this field. Furthermore, we discuss the current state of RA therapy that is based on targeting different SM subsets.
31661185 Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicentre 2020 Sep BACKGROUND: Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA). Although it is responsible of 10-20% of all RA mortality, no controlled studies are available for the treatment of RA-ILD and its therapeutic approach is still debated. AIMS: To analyse the evolution of ILD in a population of RA patients treated with tocilizumab (TCZ). METHODS: In this national multicentre study, we retrospectively collected patients with RA-ILD treated with at least one dose of TCZ. For each patient, disease activity and serological data were evaluated. Moreover, we analysed the evolution of high-resolution computed tomography (HRCT) and pulmonary function tests, including forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). RESULTS: Twenty-eight RA-ILD patients were identified (females/males 18/10, mean age 61.6 years), with a mean follow up for TCZ therapy of 30 months. At the end of follow up, FVC remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%). DLCO remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%), even though in 3 patients DLCO and FVC showed an opposite trend. HRCT remained stable in the majority (25) of cases, worsened in two patients with a usual interstitial pneumonia pattern and improved in only one case with a non-specific interstitial pneumonia pattern. CONCLUSIONS: The management of RA-ILD patients remains a critical unmet need. TCZ demonstrated a good safety profile in patients with RA-ILD and a potential effect on the stabilisation of lung involvement.
33519800 Extracellular Vesicles in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Functions 2020 In the last two decades, extracellular vesicles (EVs) have aroused wide interest among researchers in basic and clinical research. EVs, small membrane vesicles are released by almost all kinds of cells into the extracellular environment. According to many recent studies, EVs participate in immunomodulation and play an important role in the pathogenesis of autoimmune diseases. In addition, EVs have great potential in the diagnosis and therapy of autoimmune diseases. Here, we reviewed the latest research advances on the functions and mechanisms of EVs and their roles in the pathogenesis, diagnosis, and treatment of rheumatoid arthritis and systemic lupus erythematosus.
32326031 Reconsidering the Role of Melatonin in Rheumatoid Arthritis. 2020 Apr 20 Rheumatoid arthritis (RA) is an inflammatory joint disorder characterized by synovial proliferation and inflammation, with eventual joint destruction if inadequately treated. Modern therapies approved for RA target the proinflammatory cytokines or Janus kinases that mediate the initiation and progression of the disease. However, these agents fail to benefit all patients with RA, and many lose therapeutic responsiveness over time. More effective or adjuvant treatments are needed. Melatonin has shown beneficial activity in several animal models and clinical trials of inflammatory autoimmune diseases, but the role of melatonin is controversial in RA. Some research suggests that melatonin enhances proinflammatory activities and thus promotes disease activity in RA, while other work has documented substantial anti-inflammatory and immunoregulatory properties of melatonin in preclinical models of arthritis. In addition, disturbance of the circadian rhythm is associated with RA development and melatonin has been found to affect clock gene expression in joints of RA. This review summarizes current understanding about the immunopathogenic characteristics of melatonin in RA disease. Comprehensive consideration is required by clinical rheumatologists to balance the contradictory effects.
33158216 Role of Adiponectin in the Pathogenesis of Rheumatoid Arthritis. 2020 Nov 4 Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune joint disease, characterized by progressive articular damage and joint dysfunction. One of the symptoms of this disease is persistent inflammatory infiltration of the synovial membrane, the principle site of inflammation in RA. In the affected conditions, the cells of the synovial membrane, fibroblast-like synoviocytes and macrophage-like synovial cells, produce enzymes degrading cartilage and underlining bone tissue, as well as cytokines increasing the infiltration of immune cells. In patients with RA, higher levels of adiponectin are measured in the serum and synovial fluid. Adiponectin, a secretory product that is mainly white adipose tissue, is a multifunctional protein with dual anti-inflammatory and pro-inflammatory properties. Several studies underline the fact that adiponectin can play an important pro-inflammatory role in the pathophysiology of RA via stimulating the secretion of inflammatory mediators. This narrative review is devoted to the presentation of recent knowledge on the role played by one of the adipokines produced by adipose tissue-adiponectin-in the pathogenesis of rheumatoid arthritis.
31812725 Origins of rheumatoid arthritis. 2020 Jul While the exact cause of rheumatoid arthritis is unknown, several mechanisms have been described extensively. The genetic predisposition for this autoimmune disease is largely attributed to MHC class II genes, especially the main polymorphism in the HLA shared epitope. Non-genetic factors account for the rest. The best known are autoantigens to citrullinated or carbmylated proteins, although there are many others. They are recognized by an immune system with defective control mechanisms, in which regulator T-cells are unable to prevent inflammation and the destruction of tissue, joint and vascular structures (among others). Polymorphonuclear neutrophils, which are very abundant at sites of inflammation, interfere with attempts at regulation. Cell metabolism, which typically participates in fighting against the autoantigen attack, does not respond correctly to the demands, making the inflammatory phenomenon worse. This is also the case for environmental factors such as atmospheric pollution, dust, diet (especially salt intake) and infections. Inflammatory cytokines such as TNF-α, IL-1 and IL-17, are certain implicated, but not initially. They appear as a common execution pathway for a lengthy sentence following an unfortunate encounter between genetic predisposition and a harmful environment.
32080804 Cardiovascular Risk Assessment and Therapeutic Implications in Rheumatoid Arthritis. 2020 Oct Patients with rheumatoid arthritis (RA) suffer from a magnitude of excess cardiovascular risk. A paradoxical lipid pattern has been observed in rheumatoid arthritis patients where low levels of total cholesterol and low-density lipoprotein are associated with a higher risk of cardiovascular disease. This paper aims to break down the evidence explaining why patients with low to normal LDL, and total cholesterol have such excess cardiovascular risk. A component of the enhanced cardiovascular risk is systemic inflammation and the subsequent pro-atherogenic dyslipidemia patterns. Due to this "lipid paradox," current risk algorithms and guidelines designed for the general population may underestimate cardiovascular risk in patients with rheumatoid arthritis. The purpose of this paper is to critically evaluate some of the discrepancies and layers of cardiovascular risk in RA patients, the role RA medication may have in mitigating or increasing cardiovascular risk, and the possible role of statin therapy.
32988757 Contemporary imaging of rheumatoid arthritis: Clinical role of ultrasound and MRI. 2020 Dec Magnetic resonance imaging (MRI) and musculoskeletal ultrasound (MSUS) are sensitive imaging modalities used by clinicians to assist in decision-making in the management of rheumatoid arthritis (RA). This review will examine the utility of MRI and MSUS in diagnosing RA, predicting RA flares, tapering therapy, assessing remission, and examining difficult periarticular features. We will also outline the strengths and weaknesses of utilizing MRI and MSUS as outcome measures in the management of RA.
32830085 Mechanistic insights into the role of pyroptosis in rheumatoid arthritis. 2020 Nov Cell death is ascribed as an essential biological process that is fundamental for the development of an organism along with its survival. The procedure comprises of apoptosis and pyroptosis. Pyroptosis is a programmed procedure for cell death which is inflammatory in nature and this pathway gets activated via human caspase-4, human caspase-11 and human caspase-5. The activation of this process leads to release of pro-inflammatory mediators including cytokines, alarmins, IL-18 and IL-1β. The pro-inflammatory mediators released via interaction of intracellular kinases direct the development of Rheumatoid arthritis. Rheumatoid arthritis is characterized as disorder/disease that is auto-immune and chronic in nature. It involves erosions in marginal bone along with articular cartilage which is responsible for joint destruction. The cytokine along with its complex network is responsible for inflammation. The process of pyroptosis is linked with the destruction of plasma membrane, that releases these mediators and excessive release of these mediators is linked with rheumatoid arthritis.
32822056 Prevalence of rheumatoid arthritis in Edmonton and Northern Alberta. 2021 Apr OBJECTIVE: The purpose of this study was to compare and contrast the prevalence of rheumatoid arthritis in Northern Alberta estimated by health administrative data and data from a rheumatologist-based prescription database. METHODS: The study was performed using administrative health data from the province of Alberta through the local health authority. The cases and population identified in the database were reported from the year 2016. Rheumatology prescribing data was accessed through the Physician Learning Program and based on Alberta health billing data of actively practicing rheumatologists between the years 2012 and 2016. Ethics was provided by the Conjoint Health Research Ethics Boards at the University of Calgary (REB 13-0459). RESULTS: The total population of the area examined was determined to be 2,086,181. The administrative health database identified 42,354 cases of RA based on their case definition with a prevalence of 2.08%. Based on rheumatologist diagnosis and prescribing data, the number of cases identified was 11,273 cases of RA with a prevalence of 0.542%. The average percentage of identified RA patients being seen by a rheumatologist was determined to be 26.7% with the range of 19.8 to 39.9%. CONCLUSION: In conclusion, this study compares and contrasts the prevalence of rheumatoid arthritis reported by administrative data versus identification by specialists. Our study again illustrates that accuracy of case definitions when studying chronic conditions such as rheumatoid arthritis is paramount. The results also suggest a lack of access to rheumatologist services in Northern Alberta and reiterate the need for ongoing recruitment of new rheumatologists as has been highlighted previously. Key Points • The main contribution of this paper is to compare and contrast the prevalence of rheumatoid arthritis as reported by administrative data versus identification by specialists. • Our study also shows the distribution of rheumatoid arthritis in a large geographical area and illustrates a lack of access to subspecialty care in certain regions.
31865803 Synovial biopsies in inflammatory arthritis: precision medicine in rheumatoid arthritis. 2020 Mar Introduction: Synovial tissue (ST) is composed of a lining and sublining layer and is the target tissue involved in the inflammatory arthritides (IA), in which there is lining layer hyperplasia, inflammatory cell influx, macrophage recruitment and change in number and behavior of lining fibroblasts. Understanding synovial pathology has been critical in providing insights into pathogenetic mechanisms of disease and therapeutics. Pathobiological insights into ST have been underpinned by progress in molecular analytic methods; research in this area holds promise in individualizing treatment and optimizing response.Areas covered: We explore ST in IA and cover in-depth the utility of synovial biopsy and ST heterogeneity. We review recent advances in ST research and discuss implications with regards to therapeutic response. Finally, we provide perspectives on the identification of new drug targets and new diagnostic and prognostic markers.Expert opinion: ST holds the potential to individualize therapy by detecting biomarkers of diagnosis, therapeutic choice, and treatment modification in IA. Advances in molecular biology including high-throughput omics are likely to provide information that has hitherto remained unknown. ST analyzes pre- and post-treatment needs to be standard of care; only by routinely collecting and analyzing ST will we achieve the precision medicine outcomes described herein.