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ID PMID Title PublicationDate abstract
30385703 Does Rheumatoid Arthritis Really Improve During Pregnancy? A Systematic Review and Metaana 2019 Mar OBJECTIVE: We performed a systematic review and metaanalysis to assess rheumatoid arthritis (RA) disease activity during pregnancy using objective disease activity scoring systems. METHODS: A systematic review of PubMed, EMBASE/Medline, Cochrane, and LactMed databases was performed. Our inclusion criteria for analysis were prospective studies, more than 5 patients per study, and data on RA using an objective scoring system conducted by a clinician/health professional. RESULTS: Ten studies were eligible for final analysis, which included 237 patients, of which prepartum data were available for 204 patients. Postpartum disease activity was recorded in 135 pregnancies. CONCLUSION: Disease activity improved in 60% of patients with RA in pregnancy and flared in 46.7% postpartum.
31597131 Rheumatoid Arthritis-Associated Interstitial Lung Disease: Clinical Characteristics and Pr 2019 INTRODUCTION: Interstitial lung disease (ILD) is a serious extraarticular manifestation of rheumatoid arthritis (RA), but no evidence-based therapy exists. Ongoing studies investigate the role of antifibrotic therapies for progressive fibrosing ILD (PF-ILD), including RA-ILD. The aim of the present study was to investigate the frequency of PF-ILD and the clinical characteristics of RA-ILD in a well-characterised, population-based cohort. METHODS: We identified patients with RA-ILD diagnosed and followed at the ILD referral centre in Aarhus, Denmark, from 2004 to 2016. Adjusted hazard rate ratios for death were estimated using Cox regression models. The presence of PF-ILD was assessed using recently proposed definitions of relative forced vital capacity (FVC) decline ≥10%, relative diffusion capacity of the lung for carbon monoxide (DLco) decline ≥15% or worsening symptoms or a worsening radiological appearance accompanied by a ≥5 to <10% FVC decline. RESULTS: We identified 102 patients with RA-ILD, and 52% had PF-ILD. Mean follow-up was 3.8 years and median survival was 7.1 years. Thirty-eight patients died during follow-up, and most deaths were from respiratory causes. Predictors of mortality in a multivariate model were DLco and high titres of IgM rheumatoid factor. CONCLUSION: PF RA-ILD was common and the associated mortality was high.
31738612 Tyrosine kinase inhibitors for the treatment of rheumatoid arthritis: phase I to â…¡ clini 2019 Dec Introduction: Rheumatoid arthritis (RA) is a chronic, refractory disorder caused by autoimmunity in the synovial joints. Disease-modifying anti-rheumatic drugs (DMARDs) and biologicals offer remission in only two-thirds of RA patients within 3 months, hence new therapeutic approaches are necessary. Tyrosine kinase inhibitors (TKIs) are newly developed small molecule drugs which have demonstrated encouraging results in this disease.Areas covered: The key findings from phase I and II clinical trials that have investigated the use of novel TKIs in the treatment of RA are discussed. We examined the literature published between January 2014 to January 2019 using electronic databases including PubMed, Web of Science, Medline, Embase, and Google Scholar. Additional information about phase I and II trials on the ClinicalTrial.gov website up to January 2019 was also retrieved.Expert opinion: JAK inhibitors are promising drugs with sound efficacy and acceptable safety and may be beneficial to patients who do not respond to DMARDs and biologicals. The response rates among RA patients to TKIs are diverse; genetic and environmental factors may be involved in the varying responses which are closely related to the pathogenesis of RA. Future studies may reveal the underlying mechanisms of resistance and non-response.
30796506 MRI and ultrasound of the hands and wrists in rheumatoid arthritis. I. Imaging findings. 2019 May The management of patients with rheumatoid arthritis (RA) has rapidly evolved with the development of newer disease-modifying drugs and the recognition that long-term damage can be mitigated by an earlier and more-informed use of these medications. Historically, radiographs were the mainstay of imaging in RA patients, but radiographic joint narrowing and erosions are late and insensitive findings in the disease. MRI (with intravenous contrast agent) and ultrasound (with power Doppler interrogation) of the hands and wrists are able to demonstrate erosions earlier and with greater sensitivity than radiographs. More importantly, these imaging studies also depict synovitis and active soft-tissue inflammation, which represents a precursor to structural damage. Additionally, MRI can show inflammation within the bones (osteitis), which is proving to be the most important prognosticator of an aggressive disease course. Part I of this review discusses the imaging techniques, pitfalls, definitions, and comparative studies of MRI and ultrasound for identifying and quantifying erosions, synovitis, and osteitis. Part II will demonstrate how these imaging findings influence the clinical management of RA patients throughout their disease course, from presentation through clinical remission.
31491989 Proteomics Approach for the Discovery of Rheumatoid Arthritis Biomarkers Using Mass Spectr 2019 Sep 5 Rheumatoid arthritis is an autoimmune disease that causes serious functional loss in patients. Early and accurate diagnosis of rheumatoid arthritis may attenuate its severity. Despite a diagnosis guideline in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis, the practical difficulties in its diagnosis highlight the need of developing new methods for diagnosing rheumatoid arthritis. The current study aimed to identify rheumatoid arthritis diagnostic biomarkers by using a proteomics approach. Serum protein profiling was conducted using mass spectrometry, and five distinguishable biomarkers were identified therefrom. In the validation study, the five biomarkers were quantitatively verified by multiple reaction monitoring (MRM) analysis. Two proteins, namely serum amyloid A4 and vitamin D binding protein, showed high performance in distinguishing patients with rheumatoid arthritis from healthy controls. Logistic analysis was conducted to evaluate how accurately the two biomarkers distinguish patients with rheumatoid arthritis from healthy controls. The classification accuracy was 86.0% and 81.4% in patients with rheumatoid arthritis and in healthy controls, respectively. Serum amyloid A4 and vitamin D binding protein could be potential biomarkers related to the inflammatory response and joint destruction that accompany rheumatoid arthritis.
31447371 Cognitive impairment in patients with rheumatoid arthritis. 2019 Nov BACKGROUND: Neurological manifestations of Rheumatoid Arthritis (RA) are usually uncommon. However, a number of recent studies have reported that the burden of cognitive impairment in RA could be significant. We sought to explore the prevalence and clinical predictors of cognitive impairment in persons with RA. METHODS: This is a cross-sectional case-control study with patients with RA. Different trained and blinded interviewers registered clinical-epidemiological data and applied a standardized neurological assessment for each subject of the study. At baseline, functional limitations were characterized using the Health Assessment Questionnaire (HAQ). Cognitive impairment was evaluated with the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) while neuropsychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale (HADS). Using a proper statistical analysis, we compared the neurological outcomes between case and controls and we determined the clinical predictors of cognitive decline. RESULTS: A total of 210 patients with RA and 70 healthy controls were included in our study. More than two thirds of our patients were classified as cognitively impaired. The mean MMSE and MoCA scores were significantly lower in RA subjects compared to the control group (p < 0.001). Neuropshychiatric impairment was more prevalent in RA patients (59.5%) than in controls (17.1%) as well (p < 0.001). Greater functional limitations were correlated with worse MMSE, MoCA and HADS scores (p < 0.001). CONCLUSION: The findings of this study suggest that there is evidence of cognitive impairment in adults with RA.
30983549 Association between ABCB1 C3435T polymorphism and methotrexate treatment outcomes in rheum 2019 Apr Aim: This study was conducted to investigate the relationship between ABCB1 gene C3435T polymorphism and methotrexate treatment outcomes in rheumatoid arthritis patients. Methods: Seven electronic databases (PubMed, EMBASE, Web of Science, Cochrane, OVID, Chinese biomedical literature [CBM], China National Knowledge Infrastructure [CNKI] and Wanfang databases) were searched to select eligible publications until 18 July 2018. The references of relevant articles were also manually searched. The quality evaluation of the included studies was carried out according to the guidelines of the Newcastle-Ottawa Scale. Data were analyzed with Review Manager 5.3 and Stata 13.0 software. In total, 12 articles involving 2014 patients were included. Conclusion: Our results demonstrated that the ABCB1 gene C3435T polymorphism might be a reliable predictor of response to methotrexate in rheumatoid arthritis patients. However, well-designed, multicenter and large-scale prospective studies are required to further confirm the validity of our results.
30860324 [Rheumatoid arthritis-associated interstitial lung disease : new genetic data and therap 2019 Mar 6 Diffuse interstitial lung disease (ILD) is one of the most frequent extra-articular manifestation of rheumatoid arthritis (RA) and is an important factor of morbidity and mortality. However, the physiopathological mechanisms underlying RA-associated ILD remain poorly understood, and disease management is difficult in the absence of effective treatments and international guidelines. The recent identification of genetic variants and mutations similar to those observed in idiopathic pulmonary fibrosis (IPF), a disease affecting exclusively the lung, provides new insights into the understanding of RA-associated ILD. Furthermore, new antifibrotic drugs approved for the treatment of IPF, including pirfenidone and nintedanib, could also prove to be effective for RA-associated ILD. Studies are ongoing to confirm this hypothesis.
31196648 Rheumatoid Arthritis: A Severe Disease That Preventive Approaches Would Greatly Benefit. 2019 Jul With the increased understanding of the etiology and pathogenesis of rheumatoid arthritis (RA) in recent decades, the notion of disease prevention has arisen. Contemplation of potential preventive strategies must be prefaced by a clear understanding of the rationale for the prevention, as opposed to the treatment, of a disease once established. RA is the most common systemic autoimmune rheumatic disease. The worldwide prevalence is 0.24%, and the lifetime cumulative prevalence approaches 4% in women and 2% in men. RA has severe manifestations leading to chronic pain, impaired quality of life, inability to participate in social and work activities, disability, extra-articular manifestations, and premature mortality. Unfortunately, patients often experience a long duration of symptoms prior to diagnosis, owing to inadequate awareness in the general population, limitations of diagnostic assessments in the early phases of the disease, and a lack of access to rheumatologists globally. Despite the development of novel targeted therapies and substantial improvements in treatment strategies, up to 60% of patients fail to respond adequately to any particular treatment strategy, and 30% of those fail to respond to multiple agents. Therefore, there remains a large proportion of patients who fail to achieve clinical remission and patient-acceptable symptom states. Treatments for RA may be associated with a variety of complications, limiting their sustained usefulness, particularly as related to an increased risk for serious infections. Advancements in therapies have curtailed the previous main driver of mortality, cardiovascular disease, but overall mortality remains elevated in many studies of persons with RA compared to the general population. This commentary reviews the rationale in detail and introduces a clear implication that the ideal strategy would be to develop a means of preventing the onset of clinically apparent joint inflammation among individuals at risk.
31180451 Fc-gamma receptors and S100A8/A9 cause bone erosion during rheumatoid arthritis. Do they a 2019 Aug 1 Bone erosion is one of the central hallmarks of RA and is caused by excessive differentiation and activation of osteoclasts. Presence of autoantibodies in seropositive arthritis is associated with radiographic disease progression. ICs, formed by autoantibodies and their antigens, activate Fcγ-receptor signalling in immune cells, and as such stimulate inflammation-mediated bone erosion. Interestingly, ICs can also directly activate osteoclasts by binding to FcγRs on their surface. Next to autoantibodies, high levels of alarmins, among which is S100A8/A9, are typical for RA and they can further activate the immune system but also directly promote osteoclast function. Therefore, IC-activated FcγRs and S100A8/A9 might act as partners in crime to stimulate inflammation and osteoclasts differentiation and function, thereby stimulating bone erosion. This review discusses the separate roles of ICs, FcγRs and alarmins in bone erosion and sheds new light on the possible interplay between them, which could fuel bone erosion.
31148375 Tapering biologic therapy for people with rheumatoid arthritis in remission: A review of p 2019 Sep OBJECTIVES: Biologic therapies have increased the control of disease activity in rheumatoid arthritis (RA). Questions remain about tapering biologics when remission is achieved in RA. The patient perspective has to be incorporated in pragmatic applications of tapering but is rarely accounted for in clinical studies of tapering. The aim of the present review was to summarize the evidence about RA patient perspectives on biologic tapering. METHODS: We provided a narrative summary of the currently small body of research on patient perspectives retrieved through systematic searches with an emphasis on seeking qualitative research. In addition, we provided an update on relevant clinical research and financial considerations that frame the findings on patient perspectives. RESULTS: Financial considerations around commencing/continuing on biologic therapies in RA vary internationally and have implications for patient perspectives. Recent clinical studies indicate that the benefit of tapering biologic therapy when in remission are predicted by drug concentration and aspects of disease activity, severity and duration. Three major concerns have been identified from studies of patient perspectives on biologic tapering: (a) disease relapse; (b) access to treatment in the case of disease flare when tapering; and (c) local motivation for dose reduction (i.e., driven by funding or health benefit). CONCLUSIONS: More research is needed on tapering biologics, and should include studies of patient perspectives as well as health economic evaluations. Patient decision aids are a potential way of applying clinical and patient-focused evidence to help all parties come to a decision, but require developmental research and pragmatic evaluation.
31691669 [Polymorphic markers of certain genes in the development of dry keratoconjunctivitis in pa 2019 The article reviews literature on relationships between polymorphic variants of the genes THBS1, GTF2I, MUC1, TRIM21, STAT4, PTPN22 with clinical features of dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's syndrome. The development and implementation of a method for analyzing polymorphic gene variants used to diagnose dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's syndrome will allow assessment of the possibility of developing dry keratoconjunctivitis and/or its progression in patients with autoimmune diseases or in people at risk. Determination of clinical and morphological regularities of dry keratoconjunctivitis in accordance with the revealed molecular and genetic changes will contribute to better understanding of the etiology and pathogenesis of ophthalmological manifestations of autoimmune diseases, and will also help improve the diagnostics and prognosis of dry keratoconjunctivitis.
30375356 Thiol/Disulfide homeostasis in patients with rheumatoid arthritis. 2019 Mar 1 BACKGROUND: Oxidative stress may play an important role in rheumatoid arthritis (RA) etiopathogenesis. The thiol group is a very strong antioxidant. In this study, we aimed to investigate the presence of oxidative stress in patients with RA by evaluating thiol/disulfide homeostasis. MATERIAL AND METHODS: A total of 50 female RA patients and 50 healthy female controls were included in this study. Thiol and disulfide values were calculated utilizing novel methods. RESULTS: Native thiol (p < 0.001) and total thiol (p < 0.001) levels of RA patients were significantly lower compared to values in the control group. However, the disulfide (p < 0.001) levels of RA patients were strongly higher than in healthy individuals. A negative correlation was found between thiol and disease activity score-28 among the patients, whereas a positive correlation was found between disulfide and disease activity score-28 among the patients. CONCLUSION: We found that the thiol-disulfide rate deteriorated in RA patients, with the proportion of disulfide increasing. There is a strong correlation between the decrease in thiol levels, increase in disulfide levels and the disease activity scores.
31082252 Nitric Oxide-Scavenging Nanogel for Treating Rheumatoid Arthritis. 2019 Oct 9 Nitric oxide (NO), a radical gas molecule produced by nitric oxide synthase, plays a key role in the human body. However, when endogenous NO is overproduced by physiological disorders, severe inflammatory diseases such as rheumatoid arthritis (RA) can occur. Therefore, scavenging NO may be an alternative strategy for treating inflammatory disorders. In our previous study, we developed a NO-responsive macrosized hydrogel by incorporating a NO-cleavable cross-linker (NOCCL); here, we further evaluate the effectiveness of the NO-scavenging nanosized hydrogel (NO-Scv gel) for treating RA. NO-Scv gel is simply prepared by solution polymerization between acrylamide and NOCCL. When the NO-Scv gel is exposed to NO, NOCCL is readily cleaved by consuming the NO molecule, as demonstrated in a Griess assay. As expected, the NO-Scv gel reduces inflammation levels by scavenging NO in vitro and shows excellent biocompatibility. Furthermore, the more promising therapeutic effect of the NO-Scv gel in suppressing the onset of RA is observed in vivo in a mouse RA model when compared to the effects of dexamethasone, a commercial drug. Therefore, our findings suggest the potential of the NO-Scv gel for biomedical applications and further clinical translation.
31625439 Rheumatoid arthritis and cognition dysfunction: lack of association with cumulative glucoc 2019 Dec Aim: To study if cumulative glucocorticoid use could be related to cognitive impairment in rheumatoid arthritis (RA) patients.Methods: A sample of 60 RA patients and 64 controls were studied for the Mini Mental State Examination (MMSE) and depression scale (using CES-D or Center for Epidemiological Studies Depression scale). RA patients also filled a visual analogic scale (VAS) of pain and had disease activity evaluated by DAS-28 ESR (disease activity score using erythrocyte sedimentation rate). Clinical and treatment data, including cumulative dose of glucocorticoid, were collected from the charts.Results: Patients with RA had more cognitive impairment and depression than controls (p = .002 and .03, respectively). A weak and negative association of MMSE with VAS of pain was found (rho= -0.16; 95%CI = 0.49-0.004; p = .04) but not with depression and cumulative glucocorticoid doses (p = .22 and p = .52, respectively).Conclusion: Although RA patients have more cognitive impairment than controls, no correlation of this problem with cumulative glucocorticoid doses was found.
31782615 Relationship between polymorphisms in -572G/C interleukin 6 promoter gene polymorphisms (r 2020 Jan AIMS: This meta-analysis was aimed to investigate the association between -572G/C interleukin (IL)-6 gene polymorphism and occurrence risk of rheumatoid arthritis (RA). METHODS: Literature search was conducted in PubMed, Embase, Springer and Google Scholar up to November 2018. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated by Revman 5.3. RESULTS: A total of six case-control studies were included in this meta-analysis. In the allele model (G vs C), homozygous gene model (GG vs CC), recessive gene model (GG vs GC + CC), and dominant gene model (GG + GC vs CC), the pooled estimate indicated there was significant association between -572G/C IL-6 gene polymorphism and risk of RA. However, no significant statistical results were found in meta-analyses of heterozygote gene models. CONCLUSIONS: The -572G/C IL-6 gene polymorphism is associated with the risk of RA. The GG genotype may be the main contributor in increasing susceptibility to RA.
30952395 Motivational Counseling and Text Message Reminders: For Reduction of Daily Sitting Time an 2019 May Most patients with rheumatoid arthritis tend to be physically inactive and spend more time in sedentary behaviors compared with the general population. This inactive lifestyle can lead to serious health consequences, for example, increased risk of cardiovascular disease. For this reason, there is an interest in increasing participation in physical activity in patients with rheumatoid arthritis. The relatively new approach of reducing sedentary behavior and replacing it with light-intensity physical activity has been shown to be feasible and effective in promoting physical activity in patients with rheumatoid arthritis. However, methods to facilitate this behavior have not yet been fully explored.
31524005 Autoantibodies to protein-arginine deiminase (PAD) 4 in rheumatoid arthritis: immunologica 2019 Oct Introduction: The protein-arginine deiminase (PAD) 4 enzyme plays an important role in the pathogenesis of rheumatoid arthritis (RA) and also represents an antigenic target. Anti-PAD4 antibodies can be present in RA and are associated with specific clinical features. Areas covered: This review aims to analyze the current knowledge and recent findings on anti-PAD4 antibodies in RA and their clinical and immunological significance. Expert opinion: Anti-PAD4 antibodies are not currently used in clinical practice for the management of RA. Nevertheless, there is growing evidence of their relevance in RA, and of their potential utility to improve diagnosis, patient stratification, and prognosis.
31536783 Il-6 Involvement in pain, fatigue and mood disorders in rheumatoid arthritis and the effec 2019 Nov Interleukin 6 (IL-6) is a pleiotropic cytokine that plays a role in the neuroendocrine system, insulin resistance, lipid metabolism, vascular disease, mitochondrial activities, neuropsychological behaviour, and also mediates communications between the immune and central nervous system (CNS). Treatment with anti-IL-6 or anti-IL-6R agents seems to alleviate allodynia and hyperalgesia, so it may be a valid option when treating the many conditions involving pathological pain as rheumatoid arthritis.
31196657 Nomenclature for the Phases of the Development of Rheumatoid Arthritis. 2019 Jul Rheumatoid arthritis (RA) is a common immune-mediated inflammatory disease. Research on RA is increasingly focused on the earliest stages of the disease, and has provided strong evidence that clinical signs and symptoms may be preceded by a preclinical phase during which evidence of systemic autoimmunity may be present. To facilitate research in this area, a number of international initiatives have proposed definitions of the phases of disease leading up to RA. The first of these initiatives was the European League Against Rheumatism's (EULAR) set of recommendations on terminology in persons at risk for RA, which suggested that the "at-risk phases" be described in terms of patients variably having: (A) genetic risk factors for RA; (B) environmental risk factors for RA; (C) systemic autoimmunity associated with RA; (D) symptoms without clinical arthritis; and (E) unclassified arthritis. The phrase clinically suspect arthralgia (CSA) is now widely used and can be regarded as describing a subgroup of patients in phase D. A definition of CSA was recently proposed by a EULAR taskforce, and primary research has begun to explore the full range of symptoms, as well as their sensitivity and specificity alone and in combination with other factors, that characterize this phase. Similarly, immune abnormalities at mucosal and others sites that precede and/or are associated with the onset of musculoskeletal symptoms are being increasingly studied and understood. Whether some of these at-risk phases, in particular CSA, represent entities meriting their own classification criteria is an essential area for consensus and will be discussed.