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ID PMID Title PublicationDate abstract
34681582 Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis. 2021 Oct 10 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-7, IL-17, IL-21, IL-23, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-18, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.
32662676 Insights of rheumatoid arthritis biomarkers. 2021 May Rheumatoid arthritis is a chronic, autoimmune connective tissue disease. In addition to joint involvement, extra-articular changes and organ complications also occur in the course of the disease. Untreated disease leads to disability and premature death. Therefore, it is important to recognise and begin treatment early. Based on the presence of rheumatoid factor and antibodies against citrullinated peptides, we can distinguish two forms of the disease: seropositive and seronegative. Research continues to elucidate the mechanisms of the onset of the disease, as well as to uncover factors that induce and influence the activity of the disease. The presence of markers that initially appear and affect the course of the disease can potentially aid in patient treatment. In this article, we have collected biomarkers of rheumatoid arthritis that are well understood as well as those that have been recently described.
33746022 The pre-clinical phase of rheumatoid arthritis: From risk factors to prevention of arthrit 2021 May Rheumatoid arthritis (RA) is a chronic autoimmune disease considered as a multistep process spanning from the interaction of genetic (e.g., shared epitope or non-HLA loci), environmental and behavioral risk factors (e.g., smoking) leading to breaking immune tolerance and autoimmune processes such as the production of autoantibodies (e.g., antibodies against citrullinated proteins ACPA or rheumatoid factors, RF), development of the first symptoms without clinical arthritis, and, finally, the manifestation of arthritis. Despite the typical joint involvement in established RA, the pathogenesis of the disease likely begins far from joint structures: in the lungs or periodontium in association with citrullination, intestinal microbiome, or adipose tissue, which supports normal findings in synovial tissue in ACPA+ patients with arthralgia. The presence of ACPA is detectable even years before the first manifestation of RA. The pre-clinical phase of RA is the period preceding clinically apparent RA with ACPA contributing to the symptoms without subclinical inflammation. While the combination of ACPA and RF increases the risk of progression to RA by up to 10 times, increasing numbers of novel autoantibodies are to be investigated to contribute to the increased risk and pathogenesis of RA. With growing knowledge about the course of RA, new aspiration emerges to cure and even prevent RA, shifting the "window of opportunity" to the pre-clinical phases of RA. The clinical definition of individuals at risk of developing RA (clinically suspect arthralgia, CSA) makes it possible to unify these at-risk individuals' clinical characteristics for "preventive" treatment in ongoing clinical trials using mostly biological or conventional synthetic disease-modifying drugs. However, the combination of symptoms, laboratory, and imaging biomarkers may be the best approach to select the correct target at-risk population. The current review aims to explore different phases of RA and discuss the potential of (non)pharmacological intervention aiming to prevent RA.
32348230 The Role of Endostatin in Rheumatoid Arthritis. 2021 BACKGROUND: Endostatin by its therapeutic value against rheumatoid arthritis has recently gained significant interest in biomedical science. A recent study revealed that various approaches have been made to prevent rheumatoid arthritis by either controlling or inhibiting the progression of angiogenesis. OBJECTIVE: The main objective of the current manuscript is to enumerate the intrinsic role of endostatin in rheumatoid arthritis. METHODS: A thorough and detailed review of literature from the papers published from the year 1997-2019 was studied for the preparation of the current article. RESULTS: Endostatin is one such agent of the subfamily of ECM called as multiplexins obtained from proteolytic cleavage of XVIII and its carboxylic terminal fragments and is known for its antiangiogenic and antiproliferative property. The exact mechanism of endostatin is still unclear, but it acts by downregulating or inhibiting the responses of various factors, including Id1, Id3, matrix metalloproteinase, and Nuclear factor Kappa B that are liable for angiogenesis. The mutual effects on adipogenesis and angiogenesis, endostatin inhibits dietary-induced obesity and its related metabolic disorders, such as insulin resistance, glucose intolerance, and hepatic steatosis. CONCLUSION: The present review demonstrates the intrinsic usage of endostatin as a novel molecule in rheumatoid arthritis. It focuses on the status of the therapeutic potential of endostatin in inhibiting the activity of angiogenesis is also very well explored.
33728481 [Rheumatoid arthritis of the hand : Part 1: Clinical aspects]. 2021 Apr BACKGROUND: All rheumatic autoimmune diseases are associated with arthritis of the hands, whereby it is possible to differentiate between typical and atypical arthritis patterns, which are key for diagnosis. Rheumatoid arthritis is commonly associated with synovitis of the hands. While patients with disease duration of less than 2 years were previously considered to have early disease, unfavorable prognosis with delayed initiation of therapy has reduced this time frame to 3 months after symptom onset. OBJECTIVE: The aim is to provide radiologists with a systematic description of the clinical aspects of rheumatoid arthritis in order to better understand this entity so that they can confidently recognize arthritis patterns in the hands at an early stage. MATERIALS AND METHODS: Narrative review based on the current literature on the subject from radiological and rheumatological point of view. RESULTS: Synovitis of the hands is a common manifestation in rheumatoid arthritis. Knowledge of the epidemiology, prevalence, incidence, pathogenesis, genetics, etiology, biology and immunology, serology, histology, clinical presentation, the classification and diagnostic criteria, and therapy is essential for the radiologist to better understand the image-based morphologic changes associated with this complex disease and thereby gain greater confidence in the diagnosis of early stages. CONCLUSIONS: For the diagnosis of rheumatoid arthritis, the radiologist must be familiar with basic clinical knowledge to confidently analyze the patterns present in arthritis of the hands at initial diagnosis and during the course of the disease, which are essential for therapy decisions.
33728480 [Rheumatoid arthritis of the hand : Part 2: Imaging]. 2021 Apr BACKGROUND: Rheumatoid arthritis can cause joint destruction, especially joints of the hands. Diagnosed at an early stage, which often includes imaging methods, can minimize structural joint damage and resulting disabilities as well as avoid systemic manifestations such as cardiovascular damage through rapid and continuous so-called targeted treatment approaches. OBJECTIVE: The aim of this work is the systematic description and report of imaging findings in rheumatoid arthritis as the most common autoimmunologic rheumatologic disease, which is characterized by a typical pattern of synovitis of the hands. MATERIALS AND METHODS: Narrative review based on the current literature on the subject from the radiological and rheumatological point of view. RESULTS: Inflammation of the hands represents the most frequently affected area of the body in rheumatoid arthritis. Taking into consideration the topology and typical synovitis patterns of the hands, differences between early and late stages are described. Knowledge regarding image-based morphological changes associated with this complex disease, especially in the hands, is important in the differential diagnosis, especially in early stages of the disease. CONCLUSIONS: For the diagnosis of rheumatoid arthritis of the hands, the radiologist must be familiar with basic knowledge of arthritis in the hands to confidently analyze the typical patterns present in the diagnostic imaging at initial diagnosis and during the course of the disease, which serve as a guide for therapy decisions.
34650569 B Cells in Rheumatoid Arthritis：Pathogenic Mechanisms and Treatment Prospects. 2021 Rheumatoid arthritis (RA) is a common, chronic, systemic autoimmune disease, and its clinical features are the proliferation of joint synovial tissue, the formation of pannus and the destruction of cartilage. The global incidence of RA is about 1%, and it is more common in women. The basic feature of RA is the body's immune system disorders, in which autoreactive CD4(+)T cells, pathogenic B cells, M1 macrophages, inflammatory cytokines, chemokines and autoantibodies abnormally increase in the body of RA patients B cell depletion therapy has well proved the important role of B cells in the pathogenesis of RA, and the treatment of RA with B cells as a target has also been paid more and more attention. Although the inflammatory indicators in RA patients receiving B-cell depletion therapy have been significantly improved, the risk of infection and cancer has also increased, which suggests that we need to deplete pathogenic B cells instead of all B cells. However, at present we cannot distinguish between pathogenic B cells and protective B cells in RA patients. In this review, we explore fresh perspectives upon the roles of B cells in the occurrence, development and treatment of RA.
33327920 Biomarker Approach Towards Rheumatoid Arthritis Treatment. 2021 Rheumatoid arthritis is an auto-immune disorder, recognized by cartilage as well as bone destruction, which causes irreversible joint deformities, which further results in functional limitations in the patient. Genes like HLA-DRB1 and PTPN22 are likely implicated in the genetic predisposition of rheumatoid arthritis pathology. The first and foremost clinical manifestation in a person with rheumatoid arthritis is joint destruction followed by cartilage and bone destruction caused by cell-cell interactions. The cell-cell interactions are thought to be initialized through the contact of antigen-presenting cells (APC) with CD4+ cells, leading to the progression of the disease. APC includes a complex of class ІІ major histocompatibility complex molecules along with peptide antigens and binds to the receptors present on the surface of T-cells. Further, the activation of macrophages is followed by the release of various pro-inflammatory cytokines such as IL-1 and TNF-α, which lead to the secretion of enzymes that degrade proteoglycan and collagen, which in turn, increase tissue degradation. Biomarkers like IL-6, IL-12, IL-8 and IL-18, 14-3-3η, RANKL, IFN-γ, IFN-β and TGF-β have been designated as key biomarkers in disease development and progression. The study of these biomarkers is very important as they act as a molecular indicator of pathological processes that aggravate the disease.
34445645 Cell-Free DNA in Rheumatoid Arthritis. 2021 Aug 19 Endogenous DNA derived from the nuclei or mitochondria is released into the bloodstream following cell damage or death. Extracellular DNA, called cell-free DNA (cfDNA), is associated with various pathological conditions. Recently, multiple aspects of cfDNA have been assessed, including cfDNA levels, integrity, methylation, and mutations. Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis, and treatment of RA has highly varied outcomes. cfDNA in patients with RA is elevated in peripheral blood and synovial fluid and is associated with disease activity. Profiling of cfDNA in patients with RA may then be utilized in various aspects of clinical practice, such as the prediction of prognosis and treatment responses; monitoring disease state; and as a diagnostic marker. In this review, we discuss cfDNA in patients with RA, particularly the sources of cfDNA and the correlation of cfDNA with RA pathogenesis. We also highlight the potential of analyzing cfDNA profiles to guide individualized treatment approaches for RA.
34309725 Emerging epigenetic targets in rheumatoid arthritis. 2021 Dec Rheumatoid arthritis is a complex disorder that is characterized by irreversible and progressive destructions of joints, but its exact etiology remains mainly unknown. The occurrence and the progression of the disease entirely depend on environmental and genetic factors. In recent years, various epigenetic changes involving DNA methylation, histone modification, miRNA, X-chromosome inactivation, bromodomain, sirtuin, and many others were identified that were found to be linked to the activation and the aggressive phenotype in rheumatoid arthritis. Epigenetics is found to be one of the root causes, which brings changes in the heritable phenotype and is not determined by changes in the DNA sequences and understanding these epigenetic mechanisms and the pathogenesis of the disease can help in understanding the disease and various other possible ways for its control and/or prevention. The various epigenetic modification occurring are reversible and can be modulated by drugs, diet, and environmental factors. This article focuses on various epigenetic factors involved in the pathogenesis of rheumatoid arthritis. Further, various epigenetic therapies that might be successful in inhibiting these epigenetic modifications are summarized. Several therapeutic agents alter the epigenetic modifications occurring in various diseases and many of the epigenetic therapies are under pre-clinical and clinical trial. However, exploring these epigenetic prognostic biomarkers would give a broader perspective and provide more ideas and knowledge regarding the process and pathways through which the diseases occur, and also combining various therapeutic agents would show more beneficial and synergistic effects.
33833437 Cardiovascular effects of approved drugs for rheumatoid arthritis. 2021 May The risk of cardiovascular disease is increased in patients with rheumatoid arthritis compared with the general population owing to the influence of traditional and non-traditional risk factors. Inflammation has a pivotal contribution and can accelerate the atherosclerotic process. Although dampening inflammation with DMARDs should theoretically abrogate this process, evidence suggests that these drugs can also promote atherosclerosis directly and indirectly, hence adding to an increased cardiovascular burden. However, the extent and direction of the effects largely differ across drugs. Understanding how these drugs influence endothelial damage and vascular repair mechanisms is key to understanding these outcomes. NSAIDs and glucocorticoids can increase the cardiovascular risk. Conversely, conventional, biologic and targeted DMARDs control inflammation and reduce this risk, although some of these drugs can also aggravate traditional factors or thrombotic events. Given these data, the fundamental objective for clinicians should be disease control, in an individualized approach that considers the most appropriate drug for each patient, taking into account joint and cardiovascular outcomes. This Review provides a comprehensive analysis of the effects of DMARDs and other approved drugs on cardiovascular involvement in rheumatoid arthritis, from a clinical and mechanistic perspective, with a roadmap to inform the research agenda.
34366311 Work disability and rheumatoid arthritis: Predictive factors. 2021 BACKGROUND: Rheumatoid arthritis is often associated with work disability, a term used to describe the inability to be or to remain employed. Work disability is a common implication of rheumatoid arthritis. OBJECTIVE: This review aims to identify and analyze the predictive factors of work disability among patients with rheumatoid arthritis, as well as to group these factors into broader categories, based on the most current studies in this field. METHODS: An electronic search was conducted using Google Scholar, MEDLINE and PsycINFO databases. Eighty-six international journal articles were finally selected. RESULTS: The results suggest that occupational, personal, medical and societal factors are the main predictive categories of work disability for people with rheumatoid arthritis. CONCLUSIONS: Medical progress has had a positive effect on the development and the rates of work disability among patients with RA. Work disability is, however, not only defined by medical factors. Occupational, personal and societal factors interact with each other and affect the development of work disability in RA. The results of this review emphasize the need for medical and vocational therapy interventions, social support and state policies that target the work status of patients with RA. Future holistic research approaches to the field are required for a complete picture and concrete solutions with the aim of keeping patients with RA employed.
34414564 Biomaterial-based immunotherapeutic strategies for rheumatoid arthritis. 2021 Dec Rheumatoid arthritis (RA) is an extremely painful autoimmune disease characterized by chronic joint inflammation leading to the erosion of adjacent cartilage and bone. Rheumatoid arthritis pathology is primarily driven by inappropriate infiltration and activation of immune cells within the synovium of the joint. There is no cure for RA. As such, manifestation of symptoms entails lifelong management via various therapies that aim to generally dampen the immune system or impede the function of immune mediators. However, these treatment strategies lead to adverse effects such as toxicity, general immunosuppression, and increased risk of infection. In pursuit of safer and more efficacious therapies, many emerging biomaterial-based strategies are being developed to improve payload delivery, specific targeting, and dose efficacy, and to mitigate adverse reactions and toxicity. In this review, we highlight biomaterial-based approaches that are currently under investigation to circumvent the limitations of conventional RA treatments.
33635222 Rheumatoid arthritis-associated interstitial lung disease: epidemiology, risk/prognostic f 2021 Sep OBJECTIVES: To summarise the epidemiology, risk and prognostic factors, and treatment landscape of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Targeted and systematic literature reviews were conducted to characterise the epidemiology and treatment landscape associated with RA-ILD, respectively. MEDLINE®, Embase, and CENTRAL were searched via OvidSP in March 2019 and December 2018. The results were narratively summarised. RESULTS: A total of 24 and 20 publications were captured through targeted and systematic literature review, respectively. No randomised controlled trials were identified; publications were observational cohort studies, cross-sectional, or case-control. Unadjusted incidence of interstitial lung disease (ILD) ranged from 1.3/1,000 person-years for interstitial pneumonia-type ILD to 5.0/1,000 person-years for 'probable or definite ILD'. Prevalence of ILD ranged from 1.8% to 67% (median: 24.9%) and varied with case definition and sample size. Few publications identified the same risk and prognostic factors; age, male sex, duration of disease, and antibodies to cyclic citrullinated peptides were the most frequently reported risk factors for development of RA-ILD, and age was the most common predictor of mortality. Despite identification of a variety of pharmacotherapeutic interventions, assessment of the comparative efficacy and safety of the available treatments were difficult due to heterogenous reporting of outcomes and small sample size. CONCLUSIONS: A wide range of estimates were identified for incidence and prevalence of RA-ILD. Further, there was no consensus on risk and prognostic factors. Sufficiently powered clinical trials are needed to confirm the findings of the observational studies with respect to efficacy and safety of current treatments.
34463976 Periodontitis and rheumatoid arthritis: What have we learned about their connection and th 2021 Oct Rheumatoid arthritis and periodontitis are chronic inflammatory diseases defined respectively by the destruction of the articular cartilage and tooth-supporting periodontal tissues. Although the epidemiologic evidence for an association between these two diseases is still scarce, there is emerging scientific information linking specific bacterial periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, in the citrullination process, leading to autoantibody formation and compromised immunotolerance of the susceptible patient to rheumatoid arthritis. In this review, we update the existing information on the evidence, not only regarding the epidemiologic association, but also the biologic mechanisms linking these two diseases. Finally, we review information emerging from intervention studies evaluating whether periodontal treatment could influence the initiation and progression of rheumatoid arthritis.
33781492 Why It Hurts: The Mechanisms of Pain in Rheumatoid Arthritis. 2021 May Pain is a near-universal feature of rheumatoid arthritis, but peripheral joint inflammation may not suffice to explain the etiology of pain in all patients with rheumatoid arthritis. Inflammation in rheumatoid arthritis releases several algogens that may generate pain. Also, central nervous system processes may play a crucial role in the regulation and perpetuation of pain. Several methods for assessing pain in rheumatoid arthritis exist, and recently the role of assessing therapeutics in treating specific etiologies of pain has gained interest.
34831240 Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment S 2021 Nov 4 Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, and bone erosion. To prevent joint damage and physical disability as one of many symptoms of RA, early diagnosis is critical. Auto-antibodies play a pivotal clinical role in patients with systemic RA. As biomarkers, they could help to make a more efficient diagnosis, prognosis, and treatment decision. Besides auto-antibodies, several other factors are involved in the progression of RA, such as epigenetic alterations, post-translational modifications, glycosylation, autophagy, and T-cells. Understanding the interplay between these factors would contribute to a deeper insight into the causes, mechanisms, progression, and treatment of the disease. In this review, the latest RA research findings are discussed to better understand the pathogenesis, and finally, treatment strategies for RA therapy are presented, including both conventional approaches and new methods that have been developed in recent years or are currently under investigation.
34484236 Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Art 2021 BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by inflammatory cell infiltration, leading to persistent synovitis and joint destruction. The pathogenesis of RA remains unclear. This study aims to explore the immune molecular mechanism of RA through bioinformatics analysis. METHODS: Five microarray datasets and a high throughput sequencing dataset were downloaded. CIBERSORT algorithm was performed to evaluate immune cell infiltration in synovial tissues between RA and healthy control (HC). Wilcoxon test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the significantly different infiltrates of immune cells. Differentially expressed genes (DEGs) were screened by "Batch correction" and "RobustRankAggreg" methods. Functional correlation of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Candidate biomarkers were identified by cytoHubba of Cytoscape, and their diagnostic effectiveness was predicted by Receiver Operator Characteristic Curve (ROC) analysis. The association of the identified biomarkers with infiltrating immune cells was explored using Spearman's rank correlation analysis in R software. RESULTS: Ten significantly different types of immune cells between RA and HC were identified. A total of 202 DEGs were obtained by intersection of DEGs screened by two methods. The function of DEGs were significantly associated with immune cells. Five hub genes (CXCR4, CCL5, CD8A, CD247, and GZMA) were screened by R package "UpSet". CCL5+CXCR4 and GZMA+CD8A were verified to have the capability to diagnose RA and early RA with the most excellent specificity and sensitivity, respectively. The correlation between immune cells and biomarkers showed that CCL5 was positively correlated with M1 macrophages, CXCR4 was positively correlated with memory activated CD4+ T cells and follicular helper T (Tfh) cells, and GZMA was positively correlated with Tfh cells. CONCLUSIONS: CCL5, CXCR4, GZMA, and CD8A can be used as diagnostic biomarker for RA. GZMA-Tfh cells, CCL5-M1 macrophages, and CXCR4- memory activated CD4+ T cells/Tfh cells may participate in the occurrence and development of RA, especially GZMA-Tfh cells for the early pathogenesis of RA.
32358156 Ocular Manifestations in Rheumatoid Arthritis, Connective Tissue Disease, and Vasculitis: 2021 Jan 1 OBJECTIVE: Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye involvement in RA and other connective tissue diseases through a metaanalysis and literature review. METHODS: A systematic review of the literature was performed using Medline, Web of Science, and the Cochrane Library from their inceptions until January 7, 2019. Conjunctivitis, keratoconjunctivitis sicca, xeropthalmia, uveitis, eye hemorrhage, optic neuritis, papilledema, orbital disease, retinal artery/vein occlusion, macular edema, retinitis, chorioretinitis, scleritis, iridocyclitits, choroid hemorrhage, blindness, and amaurosis fugax were searched for prevalence in patients with RA, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), dermatomyositis, polymyositis, systemic sclerosis, Sjögren syndrome (SS), undifferentiated connective tissue disease, giant cell arteritis, granulomatosis polyangiitis (GPA; formerly Wegener granulomatosis), systemic vasculitis, and sarcoidosis. RESULTS: There were 3394 studies identified and 65 included. The prevalence of eye involvement was 18% in RA, 26% in GPA, 27% in giant cell arteritis, 27% in sarcoidosis, 31% in SLE, and 35% in APS. The most common manifestation was dry eye syndrome ("dry eye"; keratoconjunctivitis sicca) in most diseases analyzed, with an especially high frequency of 89% in SS. Anterior and posterior uveitis were the most common ocular complications in sarcoidosis, occurring in 16% (95% CI 3-28) and 6% (95% CI 3-9) of patients, respectively. CONCLUSION: Eye involvement is present in approximately one-fifth of patients with RA, and a one-quarter to one-third of patients with connective tissue diseases (other than SS at 89%) and vasculitis.
33243118 A Review on Rheumatoid Arthritis Interventions and Current Developments. 2021 Rheumatoid arthritis is a chronic autoimmune disorder characterized by inflammation, swelling, and joint destruction primarily affecting the peripheral joints. In recent years, RA has become an alarming concern affecting more than 1.5% of the population worldwide. The majority of the drugs in clinical trials for rheumatoid arthritis are immunomodulatory. The development of novel drugs for RA is impending and scientists are exploring new strategies through various innovative approaches for RA drug development. Treat-to-target and window of opportunity hypothesis are the new approaches that are used to treat, improve outcomes, and prevent long-term use of ineffective therapy, respectively. Novel therapeutic agents (e.g. GM-CSF inhibitors, Matrix metalloproteinase inhibitors) and delivery systems (e.g., Liposomes, Superparamagnetic iron oxide nano particles (SPIONs)) are under investigation for more target based therapy with reduced side effects and toxicity. The new drug discovery and repositioning of previously FDA-approved drugs are also being considered for chronic inflammatory disorder. The review encompasses a vast array of information, including genetics, etiology, clinical symptoms, current treatment, and newer therapeutics approaches, focused on the development of RA interventions. The introduction of the bioinformatics-based approach in RA has also been significantly discussed in the review. This review provides a general understanding of the challenges and uncertainties in the treatment of RA and summarizes the evolving scenario as well as innovative approaches taken into consideration for drug development in rheumatoid arthritis.