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ID PMID Title PublicationDate abstract
30570492 Is a Fundamental Change in the Interpretation of Rheumatoid Arthritis Disease Activity Nec 2019 Sep Disease Activity Score (DAS) composite models are moderately precise and robust measures of disease severity when they are used in rheumatoid arthritis (RA) cohorts. They are less so when used for individual patients. This is because subjective components, patient global assessment of well-being and tender joint count, modified by factors other than RA biological disease activity, often obfuscate interpretation of disease activity. Comorbidities, especially distress, can disproportionately inflate these components. Fibromyalgia, essentially synonymous with distress, pain augmentation, and depression, is a common comorbidity. Its presence and severity can be determined by the Polysymptomatic Distress Scale (PSD). The differential effects of distress and fibromyalgia syndrome on the DAS can be demonstrated by manipulating information already there: the arithmetic differences or ratios of the tender joint count and swollen joint count and comparison of the modified disease activity score with 28 joints to the disease activity score with 28 joints-patient (DAS28-derived indices that measure the contribution of the relatively objective or relatively subjective components, respectively). The potentially more objective multibiomarker disease activity might also be used to test the severity of biological RA disease activity. These tools may be used to elucidate disproportionate values for subjective DAS model components, which then should facilitate identification of the underlying process factors, including depression, for potential treatment.
31906689 Lipid profile and risks of cardiovascular diseases in conditions of rheumatoid arthritis. 2019 Winter Cardiovascular diseases (CVD) belong to the leading causes of mortality worldwide. Elevated levels of total cholesterol and LDL cholesterol are associated with increased incidence of CVD in the population. Reversely, reduction of lipoprotein levels in plasma results in a positive impact on CVD prevention. Patients with rheumatoid arthritis (RA), a chronic inflammatory disease, have markedly increased mortality risk due to CVD, despite lower lipoprotein levels in comparison with common population. This is known as the “lipid paradox”. RA itself represents an independent CVD risk factor acting as an inflammatory component. Inflammation, manifested by systemic elevated concentrations of pro-inflammatory cytokines, mainly interleukin 6 (IL-6), interleukin 1β (IL-1β) and the tumour necrosis factor α (TNF-α) in RA, is considered to be the main contributor of atherogenesis via its impact on lipoprotein metabolism and on the biology of the arterial wall. Atherosclerosis, a complex process including a number of mechanisms, is not only regarded as dysregulation of lipid metabolism, but also as a chronic inflammatory disease. This review summarizes the newest findings about the qualitative and quantitative alterations of lipids and lipoproteins affected by low-grade inflammation triggered by RA and their consequences on atherosclerosis.
31711804 Rheumatoid Arthritis Is Associated With Thromboembolic Complications Following Primary Tot 2020 Apr BACKGROUND: Recent studies have demonstrated patients with rheumatoid arthritis (RA) have deranged coagulation parameters predisposing them to venous thromboembolisms (VTEs). Therefore, the purpose of this study was to investigate whether patients who have RA undergoing primary TKA have higher rates of (1) VTEs; (2) readmission rates; and (3) costs of care. METHODS: Patients who have RA undergoing primary TKA were identified and matched to controls in a 1:5 ratio by age, sex, and comorbidities. Exclusions included patients with a history of VTEs and hypercoagulable states. Primary outcomes analyzed included rates of 90-day VTEs, along with lower extremity deep vein thromboses and pulmonary embolisms, 90-day readmission rates, in addition to day of surgery, and 90-day costs of care. A P-value less than .05 was considered statistically significant. RESULTS: Patients who have RA were found to have significantly higher incidence and odds (OR) of VTEs (1.9 vs 1.3%; OR: 1.51, P < .0001), deep vein thromboses (1.6 vs 1.1%; OR: 1.55, P < .0001), and pulmonary embolisms (0.4 vs 0.3%; OR: 1.26, P= .0001). Study group patients also had significantly higher incidence and odds of readmissions (21.6 vs 14.1%; OR: 1.67, P < .0001) compared to controls. In addition, RA patients incurred significantly higher day of surgery ($12,475.17 vs $11,428.96; P < .0001) and 90-day costs of care ($15,937.34 vs $13,678.85; P < .0001). CONCLUSION: After adjusting for age, sex, and comorbidities, the study found patients who have RA undergoing primary TKA had significantly higher rates of VTEs, readmissions, and costs.
31866617 Immune response in LPD during methotrexate administration (MTX-LPD) in rheumatoid arthriti 2019 Methotrexate (MTX) is known as a first-line synthetic disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Although the risk of LPD development increases by RA inflammation itself, observation of spontaneous regression of LPD after MTX discontinuation lead to the theory of lymphomagenic role of MTX. In this review, we focused on the several immune response involved in LPD that developed under MTX administration in RA patients.
30880553 Rac1 regulates platelet microparticles formation and rheumatoid arthritis deterioration. 2020 Platelets play important roles in blood clotting, hemostasis and wound repair, while more and more research show that platelets also have significant contributions in the process of inflammation. Rheumatoid arthritis is a chronic systemic inflammatory autoimmune disease. Platelet microparticles, which are membrane vesicles shed by activated platelets, are reported to amplify inflammation in Rheumatoid arthritis. Here we show that either platelet-specific deletion of Rac1 (Rac1(-/-)) or Rac1-specific inhibitor NSC23766 dramatically inhibit platelet-derived microparticles formation. As we all know, collagen-induced arthritis (CIA) mouse model is the most common autoimmune model of rheumatoid arthritis. Interestingly, NSC23766 alleviated the process of collagen-induced arthritis of DBA mice in vivo, including the reduced hind paw thickness and ankle stiffness, the reduction of arthritic scores and incidence of arthritis. Our work also found that NSC23766-treated CIA mouse spleen is less swollen and contains less enlarged white pulp than PBS control. The histological analysis shows that NSC23766-treated but not solvent control improve the cartilage erosion symptom in the joint of CIA mouse. Interestingly, platelet microparticles in the peripheral blood of NSC23766-treated CIA mice were decreased significantly compared with PBS-treated CIA mice. In conclusion, our work demonstrated that Rac1 inhibition alleviates collagen-induced arthritis through the decrease of platelet microparticles' release. In short, Rac1 aggravate the rheumatoid arthritis deterioration through the regulation of platelet microparticles formation.
30219863 Talk to your gut: the oral-gut microbiome axis and its immunomodulatory role in the etiolo 2019 Jan 1 Microbial communities inhabiting the human body, collectively called the microbiome, are critical modulators of immunity. This notion is underpinned by associations between changes in the microbiome and particular autoimmune disorders. Specifically, in rheumatoid arthritis, one of the most frequently occurring autoimmune disorders worldwide, changes in the oral and gut microbiomes have been implicated in the loss of tolerance against self-antigens and in increased inflammatory events promoting the damage of joints. In the present review, we highlight recently gained insights in the roles of microbes in the etiology of rheumatoid arthritis. In addition, we address important immunomodulatory processes, including biofilm formation and neutrophil function, which have been implicated in host-microbe interactions relevant for rheumatoid arthritis. Lastly, we present recent advances in the development and evaluation of emerging microbiome-based therapeutic approaches. Altogether, we conclude that the key to uncovering the etiopathogenesis of rheumatoid arthritis will lie in the immunomodulatory functions of the oral and gut microbiomes.
31518423 The role of ultrasound and magnetic resonance imaging for treat to target in rheumatoid ar 2019 Dec 1 The treat-to-target (T2T) approach has revolutionized the way we treat patients with rheumatic and musculoskeletal diseases. Recent attention has focused on imaging techniques, in particular musculoskeletal ultrasound and MRI as a focus for T2T strategies. Recently, a number of randomized clinical trials have been performed that compared tight clinical control vs control augmented by imaging techniques. While the three published trials have concluded that imaging does not add to tight clinical care, implementing imaging into the T2T strategy has actual advantages, such as the detection of subclinical involvement, and information on joint involvement/pathology and may possess potential advantages as evidenced by certain secondary endpoints. This review examines the findings of these studies and discusses the advantages and disadvantages of incorporating imaging into the T2T strategy.
32279929 HLA risk alleles and gut microbiome in ankylosing spondylitis and rheumatoid arthritis. 2019 Dec Human leukocyte antigen (HLA) alleles are associated with a variety of autoimmune diseases. The composition of gut microbiome can be influenced by host immunity, which is partially regulated by HLA. In this review, first we provide evidence from animal and human studies on: if and how HLA-B27, HLA-DRB1 (shared epitope (SE)), and other HLA alleles alter the gut microbiome, then we analyzed the data for several hypotheses to explain the mechanism(s) of HLA alleles influences on gut microbiome, and finally, we discussed several potential clinical implications of HLA alleles and microbial data, such as bacterial biomarkers for diagnosis, treatment, and the screening of high-risk population.
30280318 The folate receptor β as a macrophage-mediated imaging and therapeutic target in rheumato 2019 Feb Macrophages play a key role in the pathophysiology of rheumatoid arthritis (RA). Notably, positive correlations have been reported between synovial macrophage infiltration and disease activity as well as therapy outcome in RA patients. Hence, macrophages can serve as an important target for both imaging disease activity and drug delivery in RA. Folate receptor β (FRβ) is a glycosylphosphatidyl (GPI)-anchored plasma membrane protein being expressed on myeloid cells and activated macrophages. FRβ harbors a nanomolar binding affinity for folic acid allowing this receptor to be exploited for RA disease imaging (e.g., folate-conjugated PET tracers) and therapeutic targeting (e.g., folate antagonists and folate-conjugated drugs). This review provides an overview of these emerging applications in RA by summarizing and discussing properties of FRβ, expression of FRβ in relation to macrophage polarization, FRβ-targeted in vivo imaging modalities, and FRβ-directed drug targeting.
30685537 Pathogenic effects of anti-citrullinated protein antibodies in rheumatoid arthritis - role 2019 Oct The identification in 1998 of the main antigenic substrate recognized by autoantibodies was a dramatic turning point in our understanding of rheumatoid arthritis (RA) biology. Now, two decades later, antibodies to citrullinated proteins are viewed no longer as mere biomarkers for RA, but also as major pathophysiological factors involved in the development of bone loss and joint pain. These pathogenic effects are ascribable to abnormal autoantibody glycosylation via a pathway involving the Th17T cells. In the future, abnormal autoantibody glycosylation may serve as a disease activity biomarker and suggest novel treatment strategies.
31205940 Vitamin D as a Principal Factor in Mediating Rheumatoid Arthritis-Derived Immune Response. 2019 Rheumatoid arthritis (RA) is a systemic multifactorial autoimmune disorder. The interactions between diverse environmental and genetic factors lead to the onset of this complex autoimmune disorder. Serum levels of vitamin D (VD) are involved in the regulation of various immune responses. Vitamin D is a key signaling molecule in the human body that maintains calcium as well as phosphate homeostasis. It also regulates the functions of the immune system and, thus, can play a substantial role in the etiology of various autoimmune disorders, including RA. Low serum VD levels have been found to be associated with a higher risk of RA, although this finding has not been replicated consistently. The molecular mechanisms by which VD influences autoimmunity need to be further explored to understand how variation in plasma VD levels could affect the pathogenesis of RA. This mini-review focuses on the influence of VD and its serum levels on RA susceptibility, RA-associated complexities, treatment, and transcriptome products of key proinflammatory cytokines, along with other cytokines that are key regulators of inflammation in rheumatoid joints.
31694702 Early rheumatoid arthritis is characterised by a distinct and transient synovial fluid cyt 2019 Nov 6 A study by Raza et al., published in this journal in 2005, identified that RA patients, within 3 months of symptom onset, had a synovial fluid cytokine profile that was distinct from that of patients with other inflammatory arthritides of similarly short duration. This profile, which was transient, was characterised by cytokines of stromal and T cell origin. These findings suggested that the first few months after symptom onset were associated with changes in the early RA joint that differed from those operating at later stages. The significance of this paper's methodological approach and its findings, and how they relate to subsequent literature, are discussed.
31564299 Subclinical Treatment Targets in Rheumatology: Lessons from Randomized Clinical Trials in 2019 Nov In treat-to-target strategies, choosing the correct target is fundamental to success. The target should be associated with future good outcomes for the patient. Most rheumatic diseases are characterized by inflammation, affecting different tissues depending on the condition. Low-grade, subclinical inflammation is by definition not apparent on clinical examination, but may have significant long-term consequences for the individual. It has thus been debated whether targeting subclinical inflammation would improve long-term outcomes in rheumatoid arthritis. The authors use rheumatoid arthritis as an example to describe and discuss the status of subclinical targets in treat-to-target strategies within rheumatology.
30924010 Rheumatoid arthritis and risk of anxiety: a meta-analysis of cohort studies. 2019 Aug OBJECTIVES: Rheumatoid arthritis (RA) may increase the risk of anxiety, but results from prior studies have no consensus. Our study aimed to evaluate the relationship between RA and incident anxiety by using a quantitative meta-analysis. METHODS: A number of databases were used to gather relevant information; they included PubMed, EMBASE, and Web of Science, with the publication date of articles limited up to July 23, 2018. To evaluate their association, an odds ratio (OR) with 95% confidence interval (CI) was used. The random-effects model played a crucial role in calculating the pooled odds ratio, while subgroup analyses and sensitivity analyses were also performed. RESULTS: A total of 10 studies, including 6201 cases of anxiety and 139,875 participants, met our inclusion criteria for this meta-analysis. All individuals were without anxiety at baseline. The follow-up period ranged from 1.0 to 9.2 years. Overall, the quantitative meta-analysis suggested that subjects with RA were associated with a significantly increased risk of anxiety incidence (OR, 1.20; 95% CI, 1.03-1.39) than those without. CONCLUSION: Results of this meta-analysis indicate that individuals with RA may confer an increased risk for the development of anxiety. Future studies should explore whether clinical manifestations of RA are modifiable risk factors for anxiety.
31003546 Shedding New Light on The Role of ανβ3 and α5β1 Integrins in Rheumatoid Arthritis. 2019 Apr 18 ανβ3 and α5β1 are essential glycoproteins involved in the pathogenesis of rheumatoid arthritis (RA). Understanding of the role these integrins play in disease have been analyzed via description of cells-expressing ανβ3 and α5β1 and their mediators to trigger inflammation. ανβ3 and α5β1 facilitate cells-ECM and cell-cell communication, producing pro-inflammatory factors. Pro-inflammatory factors are essential for the building of undesirable new blood vessels termed angiogenesis which can further lead to destruction of bones and joints. Despite many attempts to target these glycoproteins, there are still some problems, therefore, there is still interest in understanding the synergistic role these integrins play in the pathogenesis of RA. The purpose of this review is to gain insights into the biological effects of ανβ3 and α5β1 in synovial tissues that are relevant to pathogenesis and therapy of RA.
30875457 Prevalence of Arthritis and Rheumatoid Arthritis in Coal Mining Counties of the United Sta 2019 Sep OBJECTIVE: Exposure to inhaled mineral dust, in particular silica, is associated with increased odds of rheumatoid arthritis (RA) and other autoimmune diseases. We studied the association of RA with work-related coal and silica exposure in the Appalachian region of the US. METHODS: We carried out a random-digit dialed telephone survey in selected counties in Appalachia that had elevated coal workers' pneumoconiosis mortality. Our study cohort included men ages ≥50 with any employment history, and we assessed exposure to coal mining employment, other work-related dust, and ergonomic factors. We ascertained self-reported physician diagnosis of any arthritis and of RA with glucocorticoid treatment. We used multivariable logistic regression analysis to estimate the odds ratios (ORs) and associated population attributable fraction (PAF) estimates. RESULTS: Among the 973 men who met study entry criteria (mean ± SD ages 66 ± 10 years; 54% ever smokers), 266 (27%) reported coal mining work and 189 (19%) reported other work-related silica exposure. There were 517 men (53%), who reported any arthritis and 112 (12%) whose disease met the study definition of RA. Adjusting for covariates, coal mining was associated with elevated odds of RA (OR 3.6 [95% confidence interval (95% CI) 2.1-6.2]), which accounted for a PAF of 33% (95% CI 26-40%) of the men studied. For any arthritis, the coal mining-associated OR was 2.3 (95% CI 1.6-3.2), with an associated PAF of 20% (95% CI 14-25%). CONCLUSION: In this population of older males living in a coal mining region, we estimated that 20% of arthritis and 33% of RA may be attributable to coal mining work.
31196653 Impact of Adverse Events Associated With Medications in the Treatment and Prevention of Rh 2019 Jul PURPOSE: Treatments for rheumatoid arthritis (RA) over the last few decades have transformed the future outlook of the disease. Although patients with clinically apparent RA have a number of therapeutic options, all are associated with the risk of adverse events (AEs). Such therapeutics, facilitated by the identification of novel biomarkers and environmental and genetic factors to predict RA, may allow early detection, prompt treatment, and prevention before the future development of clinically apparent disease. Before choosing such treatments to make informed decisions in this context, however, accurate quantification of benefits and harms of such treatments is vital for participants without symptoms. This review summarizes the AEs reported in trials in preclinical or very early RA, the frequency and risk of primary AEs of concern associated with disease-modifying antirheumatic drugs (conventional, biologic, and targeted), glucocorticoids, and analgesia in clinically apparent RA. Also summarized is the evidence to date to support the quantification of benefit and harms incorporating patient preferences. METHODS: This analysis is a narrative review in which individual searches were performed in PubMed and EMBASE for each drug and topic outlined in the review. FINDINGS: Current therapies in RA can result in a considerable burden of AEs (serious and nonserious) depending on the individual's baseline risk. The absolute risk of serious AEs to treatments reported in individuals at risk of RA, undifferentiated, or very early inflammatory arthritis trials was low; however, nonserious AEs were not consistently reported. If such therapies prove effective at preventing the onset of RA in high-risk patients, incorporating patient preferences as well as robust quantification of benefits and harms to inform decisions is imperative. Patients' perceptions about treatment in this context may be risk averse or benefit driven. The risk of AEs that may not reverse after drug cessation, such as serious infection and malignancy, seem to be important AEs in such decision-making. IMPLICATIONS: The impact of AEs in response to potentially preventative treatment is an important consideration for individuals at high risk of developing RA with minimal symptoms. Robust quantification of treatment effect given baseline risk versus the risks of developing all AEs (including those that may affect quality of life), while incorporating participants' views, will be necessary for future informed decision-making.
30806723 MR and ultrasound of the hands and wrists in rheumatoid arthritis. Part II. Added clinical 2019 Jun Advanced imaging has become just as vital for diagnosing, staging, and monitoring disease in rheumatoid arthritis (RA) patients as it is for cancer patients. Part 1 of this review discussed synovitis, tenosynovitis, erosions, and osteitis-key imaging findings that occur in patients with RA. Part 2 will now show how these features, in combination with clinical and serologic data, can assist clinical decision-making at various stages of a patient's disease course. Specifically, assessing current disease activity and prognosticating future aggressiveness inform treatment decisions at initial presentation, during medical treatment, and at clinical remission. In addition to summarizing the current literature on advanced imaging in RA, clinical examples from different stages throughout the disease course will illustrate practical approaches for applying these research results. Last, this review will describe potential future roles of imaging in RA patients.
30204715 Effectiveness of non-pharmacological and non-surgical interventions on the impact of rheum 2019 Jan The questions of this review are.
31309293 Kuwait association of rheumatology 2018 treatment recommendations for patients with rheuma 2019 Sep The Kuwait Association of Rheumatology (KAR) aimed to develop a set of recommendations for the treatment of patients with rheumatoid arthritis (RA), tailored to the unique patient population and healthcare system of Kuwait. Each recommendation was developed based on expert opinion and evaluation of clinical practice guidelines from other international and national rheumatology societies. Online surveys were conducted to collate feedback on each KAR member's level of agreement (LoA) with definitions of disease-/treatment-related terms used and the draft recommendations. Definitions/recommendations achieving a pre-defined cut-off value of ≥ 70% agreement were accepted for inclusion. Remaining statements were discussed and revised at a face-to-face meeting, with further modifications until consensus was reached. A final online survey was used to collect feedback on each KAR member's LoA with the final set of recommendation statements on a scale of 0 (complete disagreement) to 10 (complete agreement). Group consensus was achieved on 66 recommendation statements, including 3 overarching principles addressing the pharmacological treatment and management of RA. Recommendations focused on treatment of early RA, established RA, patients with high-risk comorbidities, women during pregnancy and breastfeeding, and screening and treatment of opportunistic infections. The KAR 2018 Treatment Recommendations for RA reported here are based on a synthesis of other national/international guidelines, supporting literature, and expert consensus considering the Kuwaiti healthcare system and RA patient population. These recommendations aim to inform the clinical decisions of rheumatologists treating patients in Kuwait, and to promote best practices, enhance alignment and improve the treatment experience for patients.