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ID PMID Title PublicationDate abstract
27919189 A review on interleukins: The key manipulators in rheumatoid arthritis. 2017 Sep Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with weakening of bones and joint pain. It primarily involves autoimmunity, matrix destruction, osteoclastogenesis, inflammation, and angiogenesis. Numerous cellular and humoral components of the immune system are involved in the etiology of diseases; however, the cardinal part is played by the inter-cellular signaling messengers called cytokines. Interleukins is a vaguely defined sub-class of cytokines that are abundantly found in the RA patients. The multifariousness and diversity in the function of the interleukins make them very likely to be associated with the pathogenesis in multiple ways. Nonetheless, the variety in opinions of researchers globally has led to contentious inferences. Ergo, in this review we have amalgamated the views of researchers from the past two decades till date to provide a comprehensive report about the role of interleukins in rheumatoid arthritis.
28451785 Environmental factors and hormones in the development of rheumatoid arthritis. 2017 Jun The etiopathogenesis of rheumatoid arthritis (RA) is partially understood. Genetic, environmental, and hormonal factors and their interactions are considered to play an important role on disease development. The relative contribution of environmental factors to RA development is probably larger than previously thought. The aim of this review is to appraise robust evidence about the role of environmental and hormonal risk factors for RA. We will discuss inhaled pollutants, nutritional habits, infectious, hormonal, and reproductive factors. As some of these factors are potentially modifiable, understanding their impact on RA development opens new opportunities for potential interventions and disease prevention.
28836487 DNA methylation as a marker of response in rheumatoid arthritis. 2017 Sep Rheumatoid arthritis (RA) is a complex disease affecting approximately 0.5-1% of the population. While there are effective biologic therapies, in up to 40% of patients, disease activity remains inadequately controlled. Therefore, identifying factors that predict, prior to the initiation of therapy, which patients are likely to respond best to which treatment is a research priority and DNA methylation is increasingly being explored as a potential theranostic biomarker. DNA methylation is thought to play a role in RA disease pathogenesis and in mediating the relationship between genetic variants and patient outcomes. The role of DNA methylation has been most extensively explored in cancer medicine, where it has been shown to be predictive of treatment response. Studies in RA, however, are in their infancy and, while showing promise, further investigation in well-powered studies is warranted.
29094223 Can Probiotic Supplements Improve Outcomes in Rheumatoid Arthritis? 2017 Nov 2 PURPOSE OF REVIEW: The purpose of this review is to frame the discussion of the potential use of probiotics for the management of rheumatoid arthritis (RA) in the historical and scientific context linking the human microbiota to the etiology, pathogenesis, and treatment of RA. Given this context, the review then details the clinical trials that have been carried out so far that have tried to address the question. RECENT FINDINGS: A variety of laboratory and clinical observations link the flora of the oral cavity and lower gastrointestinal tract with citrullination, as well as immunological alterations that may contribute to the risk of developing RA. Clinical trials to date have been small and mostly short term. Statistically significant change in certain disparate clinical endpoints has been reported, but these endpoints have varied from study to study and have been of limited clinical significance. No consistent, robust impact on patient reported, or laboratory outcome measures has emerged from clinical trials so far. There remain theoretical reasons to further investigate the use of probiotics as adjunctive therapies for autoimmune disease, but changes in trial design may be needed to reveal the benefit of this intervention.
28236220 The function of myeloid dendritic cells in rheumatoid arthritis. 2017 Jul Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes joint pain, inflammation, and loss of function. Disease pathogenesis involves activation and proliferation of autoreactive pro-inflammatory effector T cells. While the details of RA onset and progression remain controversial, dendritic cell (DC) numbers dramatically increase in the synovial joint tissues of RA patients. Based on their key functions as antigen-presenting cells and inducers of T cell differentiation, DCs may play an important role in the initiation of joint inflammation. Myeloid DC contributions are likely central to the development of RA, as they are more efficient at antigen presentation in comparison with their closely related cousins, plasmacytoid DCs. Synovial fluid in the joints of RA patients is enriched with pro-inflammatory cytokines and chemokines, which may stimulate or result from DC activation. Epidemiological evidence indicates that smoking and periodontal infection are major environmental risk factors for RA development. In this review, factors in the synovial environment that contribute to altered myeloid DC functions in RA and the effects of environmental risk factors on myeloid DCs are described.
29205904 Dosing down and then discontinuing biologic therapy in rheumatoid arthritis: a review of t 2018 Feb AIM: To review the published studies that dose down and then discontinue biologic therapy in patients with rheumatoid arthritis (RA), particularly concerning the criteria for such dosing and the impact on clinical outcomes. METHODS: Published studies conducted in patients with RA that sequentially decreased the dose and then discontinued therapy were included if one or more of the following biologic disease modifying antirheumatic drugs (bDMARDs) was evaluated: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab or tocilizumab. RESULTS: Five studies qualified for inclusion. The populations of patients with RA were heterogeneous among the studies; patients were required to have low disease activity (LDA) or to be in remission prior to dose titration. Approximately 25-65% of patients successfully decreased and in some cases, discontinued the bDMARD. However, the flare rate was higher than for the patients who remained on a standard dose. The only variable that predicted relapse in more than one study was down-titration of the bDMARD dose. CONCLUSION: In patients who have achieved LDA or remission, down-titration and discontinuation of bDMARD therapy may be attempted, with careful monitoring. However, it is likely that some patients will flare, and it is not known how to predict these patients.
26496781 The Role of Wrist Fusion and Wrist Arthroplasty in Rheumatoid Arthritis. 2017 Rheumatoid arthritis is the most common form of inflammatory arthritis with a predilection for the hand and wrist. The aggressive nature of the disease can lead to severe joint destruction causing significant disability. Surgical options for pan-carpal arthritis include total wrist arthroplasty and total wrist fusion both with varying outcomes, yet both have a role in the carefully selected patients. Fusion remains a popular procedure with consistent reliable results with few complications. We present a review of current evidence, indications and guidance for both fusion and arthroplasty in rheumatoid arthritis.
29120570 Early referral improves long-term outcomes in rheumatoid arthritis. 2017 May Rheumatoid arthritis (RA) is a common, chronic systemic inflammatory disease of unclear aetiology leading to synovial hypertrophy and joint inflammation. It typically presents with symmetrical polyarthritis of small joints of the hands or feet, but can also involve larger joints, and have associated extra-articular manifestations. Diagnosis is based on duration of symptoms, joint distribution, level of inflammatory markers and autoantibodies i.e. rheumatoid factor(RhF) and anty-cyclic citrullinated peptide (CCP) antibodies. The presence of synovitis or effusion, either clinical or subclinical, seen on ultrasound or MRI, is essential for diagnosis. RA can sometimes present with a large joint monoarthritis or oligoarthritis. Although this is an atypical presentation, a diagnosis can be made in the presence of suggestive serology and/or histology. In cases presenting with monoarthritis, careful assessment for differential diagnoses is needed, particularly in the elderly population where other conditions such as gout, calcium pyrophosphate deposition disease and osteoarthritis are common. Early referral of patients with suspected synovitis via the rapid access early inflammatory arthritis clinic results in significant improvements in long-term outcomes. Hence it is important to consider early referral for individuals with synovitis, particularly if this is affecting small joints.
28662826 Metalloproteinases in Rheumatoid Arthritis: Potential Therapeutic Targets to Improve Curre 2017 Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by the destruction of joint tissues including cartilage and bone. Cartilage degradation is attributed to metalloproteinases (MPs) that belong to matrix metalloproteinase family and a disintegrin and metalloprotease with thrombospondin type 1 motifs produced by inflamed joint tissues. In addition, an enzyme that belongs to a disintegrin and metalloprotease family is also involved in release of inflammatory cytokines. Several highly selective inhibitors have been developed for MPs thought to play a role in RA pathogenesis and examining these inhibitors as potential drugs is becoming realistic. This chapter discusses recent reports on MPs in RA and their potential as a therapeutic target.
29064808 [The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literatur 2017 Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.
28631608 One year in review 2017: pathogenesis of rheumatoid arthritis. 2017 May Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. It has been postulated that a high-risk genetic background, in combination with epigenetic marks and environmental exposures, leads to a cascade of events inducing synovitis and consequent destructive arthritis. The clinical picture of joint involvement in RA is the result of chronic inflammation of the synovium, characterised by interactions of resident cells such as fibroblast-like synoviocytes (FLS) with cells of the innate (e.g. macrophages, dendritic cells, mast cells and NK cells, neutrophils) and adaptive immune system (e.g. B and T lymphocytes). Currently, our understanding of the role of innate and adaptive immunity in the pathogenesis of RA is expanding. The concept of how immune responses contribute to the disease has dramatically evolved over the last 50 years. Shedding some light on the different aspects of RA pathogenesis will help to identify new targets for the development of disease-modifying therapies. Thus, in this review we report new insights in RA pathogenesis, resulting from a literature research date published in the last year.
27650675 Treating rheumatoid arthritis to target: physician and patient adherence issues in contemp 2017 Jun Development of the treat-to-target (T2T) strategy, the process whereby drug therapy is adjusted until the therapeutic goal is achieved, has revolutionized how rheumatoid arthritis (RA) patients are treated. With the advent of T2T, the management of RA is more effective than ever, with the possibility of remission and other favorable clinical and patient-reported outcomes. Effective implementation of a T2T strategy in routine clinical practice mainly depends on the long-term commitment of physician and patient to T2T treatment recommendations. However, as T2T is a complex process involving aggressive early management with several steps of therapy modifications requiring frequent close monitoring of disease activity and drug toxicities, it may be more liable to suboptimal adherence in real-life clinical practice. The aim of the review is to present key issues related to patient medication adherence and physician adherence to the current RA treatment recommendations and their importance in optimizing the outcome of treatment in RA treated according to T2T strategy.
28524646 Cervical spine involvement risk factors in rheumatoid arthritis: a meta-analysis. 2017 May AIM: This study aims to discuss risk factors associated with cervical spine involvement (CSI) in patients with rheumatoid arthritis (RA). METHODS: A literature search was performed in Medline, EMBASE, Web of Science and CBMdisc databases for potential studies published before October 2016. The clinical and laboratory data were extracted, and a meta-analysis was performed to evaluate the risk factors for CSI in RA patients. RESULTS: Twelve studies involving a total of 2750 cases with RA and 733 CSI (26.65%) were eligible and included in this meta-analysis. The results showed that risk factors for CSI were female (odds ratio [OR] = 1.37, 95% confidence interval [CI]: 1.079-1.74), positive rheumatoid factor (RF) (OR = 1.351, 95% CI: 1.084-1.683), long-term corticosteroids treatment (OR = 2.208, 95% CI: 1.732-2.815), erosion in hands or feet (OR = 2.559, 95% CI: 1.985-3.299), age (weighted mean difference [WMD] = -2.464 years, 95% CI: -3.688 to -1.240), RA duration (WMD = 1.495 years, 95% CI: 0.870-2.121), erythrocyte sedimentation rate (ESR) level (standard mean difference [SMD] = 0.288, 95% CI: 0.161-0.41), C-reactive protein (CRP) level (SMD = 0.288, 95% CI: 0.161-0.415), Disease Activity Score of 28 joints (SMD = 0.5, 95% CI: 0.303-0.697). CONCLUSION: The significant risk factors for CSI in RA were female gender, positive RF, long-term corticosteroids treatment, peripheral joints erosions, younger age, long RA duration, markers of higher disease activity (ESR, CRP and Disease Activity Score).
27977821 A Possible Link Between Rheumatoid Arthritis and Periodontitis: A Systematic Review and Me 2017 Jan/Feb Previous studies have shown that patients with rheumatoid arthritis (RA) have a higher susceptibility to periodontitis, but the results of individual studies remain controversial. The aim of the present meta-analysis was to comprehensively evaluate the association between RA and periodontitis. A systematic literature search was conducted in PubMed and EMBASE. Data were extracted using standardized forms, and odds ratios (OR) with 95% confidence intervals (CI) were calculated for each study. Pooled data were estimated by fixed- and random-effects models if appropriate. Eight case-control studies were included in the present study. Study size ranged from 104 to 151,569 participants. The prevalence of periodontitis in RA patients ranged from 15.5% to 100%, compared with 10.0% to 82.1% in controls. In group 1 (control) and group 2, the heterogeneity was 38% and 11%, respectively. Using fixed-effects analysis, the overall pooled estimates of the ORs for periodontitis were 4.68 (95% CI: 3.11-7.05) and 1.28 (95% CI: 1.24-1.33) in groups 1 and 2, respectively. This meta-analysis indicates that RA was significantly associated with increased overall risk of periodontitis.
27481831 Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental 2017 Feb OBJECTIVE: Current research in rheumatoid arthritis focuses on preclinical disease phases as it is hypothesised that early preclinical treatment might prevent progression to full-blown disease. Since performance of studies in prearthritis phases in humans is challenging, animal models offer an opportunity to evaluate preventive treatments. We performed a systematic literature review and summarised treatment effects during different stages of arthritis development in animal models. METHODS: Eight medical literature databases were systematically searched. Studies were selected if they reported effects of synthetic or biological disease-modifying antirheumatic drugs in animal models of arthritis (collagen-induced arthritis and adjuvant-induced arthritis) on arthritis severity, as measured with arthritis severity scores, paw swelling or paw volume. Quality was assessed using an 11-item checklist. Study characteristics were extracted and effect sizes obtained in high-quality studies were summarised in meta-analyses. Studies were categorised into three groups: prophylactic (prior to generation of autoantibody response), prearthritis (after induction of autoantibody response) and therapeutic intervention (after arthritis development). RESULTS: Out of 1415 screened articles, 22 studies (including n=712 animals) were eligible of good quality and included in meta-analyses. Prophylactic (16 experiments, n=312 animals) and prearthritis treatment (9 experiments, n=156 animals) both were associated with a reduction of arthritis severity (p<0.001 and p=0.005, respectively). Stratified analyses for different antirheumatic drugs initiated in the prearthritis phase suggested higher efficacy of methotrexate than of anti-tumour necrosis factor. CONCLUSIONS: Data of experimental studies in animal models of arthritis suggest that prophylactic and prearthritis treatment strategies are effective and hint at differences in efficacy between antirheumatic drugs.
28051887 Autoimmunity as a trigger for structural bone damage in rheumatoid arthritis. 2017 Mar Bone loss is a central feature of rheumatoid arthritis (RA). It is considered to represent a sign of irreversible structural damage triggered by chronic inflammation. Recent evidence, however, suggests that autoantibodies are an important and earlier driver for bone damage in RA. This article summarizes current evidence for the role of RA-related autoantibodies in mediating bone loss. Rheumatoid factor and antibodies recognizing modified (citrullinated) proteins are the central features of autoimmunity in RA patients. Despite being used as diagnostic markers for many years, ascertaining the differentiation of RA from other forms of inflammatory arthritides, the role of these antibodies as pathogenic players has long been unrecognized. Recently, several pieces of evidence suggested that bone-resorbing osteoclasts are highly responsive to RA-related autoantibodies, providing a novel link between autoimmunity and bone. These developments have allowed unraveling the underlying mechanisms, which are responsible for the well-known clinical observation that RA-related autoantibodies are associated with a more severe disease course. At present, rheumatoid factor and antibodies recognizing citrullinated proteins are considered as potent osteoclast inducers and triggers for bone loss in arthritis.
28774454 What the Rheumatologist Is Looking for and What the Radiologist Should Know in Imaging for 2017 Sep This article outlines what the rheumatologist is looking for and wants to know in the clinical diagnosis and imaging of rheumatoid arthritis, and what the radiologist should know to facilitate this.
29221601 Magnetic resonance imaging in individuals at risk of rheumatoid arthritis. 2017 Feb Individuals with rheumatoid arthritis (RA) benefit from early diagnosis and initiation of therapy. There can be delays in both due to diagnostic uncertainties. Imaging modalities, including magnetic resonance imaging (MRI), can detect inflammation earlier than clinical examination alone in early RA patients. Furthermore, the predictive role of MRI for the future development of RA has recently been explored in 'at-risk' individuals. This review details the use of MRI in early and undifferentiated arthritis and summarises the studies to date in individuals at risk of RA.
27976535 Patient goals in rheumatoid arthritis care: A systematic review and qualitative synthesis. 2017 Dec OBJECTIVE: During the clinical encounter, rheumatoid arthritis (RA) patient goals for care often go unexplored. The aim of the present systematic review was to identify needs, goals and expectations of RA patients in order better to guide systematic elicitation of patient goals in clinical encounters. METHODS: An academic librarian searched MEDLINE, PsychINFO and the Cochrane Library using a specialized algorithm developed to identify articles about patient goals for RA care. Investigators screened search results according to prespecified inclusion criteria and then reviewed included articles and synthesized the evidence qualitatively, utilizing an inductive approach. RESULTS: A total of 909 titles were retrieved in the literature search, of which 871 were excluded after a title/abstract screen. Of the remaining 38, 22 papers were included in the final review. Investigators identified four major themes in the literature: (a) the bodily experience of RA; (b) achieving normalcy and maintaining wellness; (c) social connectedness and support; and (d) interpersonal and healthcare system interactions. CONCLUSION: Patients' goals when receiving care for RA are multidimensional and span several facets of everyday life. Goals for RA care should be collaboratively developed between patients and providers, with particular attention to the patient's life context and priorities.
27990682 Is there potential for therapeutic drug monitoring of biologic agents in rheumatoid arthri 2017 May The use of biologics has significantly changed the management of rheumatoid arthritis over the last decade, becoming the cornerstone treatment for many patients. The current therapeutic arsenal consists of just under 10 biologic agents, with four different mechanisms of action. Several studies have demonstrated a large interindividual pharmacokinetic variability, which translates to unpredictability in clinical response among individuals. The present review focuses on the pharmacokinetics and pharmacodynamics of biologic agents approved for rheumatoid arthritis. The literature relating to their concentration-effect relationship and the use of pharmacokinetic-pharmacodynamic modelling to optimize drug regimens is analysed. Due to the scarcity and complexity of these studies, the current dosing strategy is based on clinical indexes/aspects. In general, dose individualization for biologics should be implemented increasingly in clinical practice as there is a direct benefit for treated rheumatoid arthritis patients. Moreover, there is an indirect benefit in terms of cost-effectiveness.