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ID PMID Title PublicationDate abstract
22265260 Joint appendages: the structures which have historically been overlooked in arthritis rese 2011 Dec Rheumatologists have largely conceptualised joint disease in inflammatory and degenerative arthritis in terms of bone, cartilage and the synovial lining, but have tended to overlook other integral components of the joints which are attached close to joint margins. We discuss these structures under the umbrella term of 'appendages'. These structures include ligaments, tendons, entheses or joint insertions, regional fibrocartilages, bursae and other peri-articular joint structures including fat pads and nails. In this review, we highlight how these structures play key pathophysiological roles in inflammatory arthritis and we emphasise how an understanding of these structures is collectively important for both clinical practice and future rheumatological research.
22538842 Low-level laser therapy in different stages of rheumatoid arthritis: a histological study. 2013 Feb Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology. Treatment of RA is very complex, and in the past years, some studies have investigated the use of low-level laser therapy (LLLT) in treatment of RA. However, it remains unknown if LLLT can modulate early and late stages of RA. With this perspective in mind, we evaluated histological aspects of LLLT effects in different RA progression stages in the knee. It was performed a collagen-induced RA model, and 20 male Wistar rats were divided into 4 experimental groups: a non-injured and non-treated control group, a RA non-treated group, a group treated with LLLT (780 nm, 22 mW, 0.10 W/cm(2), spot area of 0.214 cm(2), 7.7 J/cm(2), 75 s, 1.65 J per point, continuous mode) from 12th hour after collagen-induced RA, and a group treated with LLLT from 7th day after RA induction with same LLLT parameters. LLLT treatments were performed once per day. All animals were sacrificed at the 14th day from RA induction and articular tissue was collected in order to perform histological analyses related to inflammatory process. We observed that LLLT both at early and late RA progression stages significantly improved mononuclear inflammatory cells, exudate protein, medullary hemorrhage, hyperemia, necrosis, distribution of fibrocartilage, and chondroblasts and osteoblasts compared to RA group (p < 0.05). We can conclude that LLLT is able to modulate inflammatory response both in early as well as in late progression stages of RA.
21062850 PADI4 polymorphism predisposes male smokers to rheumatoid arthritis. 2011 Mar OBJECTIVE: To elucidate the differential role of peptidyl arginine deiminase 4 (PADI4) polymorphism in rheumatoid arthritis (RA) between Asian and European populations, possible gene-environmental interactions among the PADI4 polymorphism, sex and smoking status were analysed. METHODS: Three independent sets of case-control samples were genotyped for single-nucleotide polymorphisms in PADI4; Japanese samples (first set, 1019 RA patients, 907 controls; second set, 999 RA patients, 1128 controls) using TaqMan assays and Dutch samples (635 RA patients, 391 controls) using Sequenom MassARRAY platform. The association of PADI4 with RA susceptibility was evaluated by smoking status and sex in contingency tables and logistic regression models. RESULTS: In the first set of Japanese samples, PADI4 polymorphism (rs1748033) showed a greater risk in men (OR(allele) 1.39; 95% CI 1.10 to 1.76; p(trend)=0.0054) than in women and in ever-smokers (OR(allele) 1.25; 95% CI 1.02 to 1.53; p(trend)=0.032) than in never-smokers. Moreover, the highest risk was seen in male ever-smokers (OR(allele) 1.46; 95% CI 1.12 to 1.90; p(trend)=0.0047). Similar trends were observed in the second set of Japanese samples as well as in Dutch samples. CONCLUSION: PADI4 polymorphism highly predisposes male smokers to RA, and the genetic heterogeneity observed between Asian and European populations may be partly explained by differences in smoking prevalence among men.
21572151 Continuation of methotrexate resulted in better clinical and radiographic outcomes than di 2011 Aug OBJECTIVE: The aim of the Efficacy and Safety of Etanercept on Active Rheumatoid Arthritis Despite Methotrexate Therapy in Japan (JESMR) study is to compare the efficacy of continuation versus discontinuation of methotrexate (MTX) when starting etanercept (ETN) in patients with active rheumatoid arthritis (RA). METHODS: In total, 151 patients with active RA who had been taking MTX were randomized to either ETN 25 mg twice a week with 6-8 mg/week MTX (the E+M group), or ETN alone (the E group). The primary endpoint at Week 52 was the radiographic progression assessed by van der Heijde-modified Sharp score. RESULTS: The mean progression in total score at Week 52 was not significantly different, statistically, between the E+M group and the E group (0.8 vs 3.6, respectively; p = 0.06). However, a significant difference was observed in radiographic progression between Weeks 24 and 52 (0.3 vs 2.5; p = 0.03), and the mean progression of the erosion score was negative in the E+M group, which was significantly better than the E group at Week 52 (-0.2 vs 1.8; p = 0.02). Clinically, the cumulative probability plot of the American College of Rheumatology (ACR)-N values at Week 52 clearly demonstrated a superior response in the E+M group than in the E group. ACR20, 50, and 70 response rates at Week 52 in the E+M group (86.3%, 76.7%, and 50.7%) were significantly greater than those in the E group (63.8%; p = 0.003, 43.5%; p < 0.0001 and 29.0%; p = 0.01, respectively). CONCLUSION: MTX should be continued when starting ETN in patients with active RA. (ClinicalTrials.gov: NCT00688103).
22976394 Association of single nucleotide polymorphisms (SNPs) of PADI4 gene with rheumatoid arthri 2012 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting ~ 1% of the population worldwide. The genome wide association studies on RA patients revealed linkage with 1p36 locus containing peptidyl arginine deiminase 4 (PADI4) genes. Case-control association studies and mRNA stability assays reported the association of PADI4 gene with RA in Korean and Japanese populations. However, such association was not found in Spanish population. Differences in the association of PADI4 with RA in different populations prompted the present study in Indian population. Anti-CCP antibodies, RF antibody, disease activity scores at 28 joints (DAS28) and mutations in three exons of PADI4 were investigated in RA patients and control group. Among the patients anti-CCP antibody levels were found to be associated with high DAS28 values (r = 0.4526, P < 0.0001). Polymorphism in exon-4 (padi4_104, [rs1748033]) of PADI4 showed significant association of 'C' allele with RA in the study population (P = 0.0008). Polymorphism in exon-3 (padi4_92, [rs874881]) also exhibited moderate association with the disease (P = 0.075). However, no association of the disease was found with the SNPs padi4_89 [rs11203366] and padi4_90 [rs11203367] in exon-2 of PADI4.
22494429 MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. 2012 Jun 1 Rheumatoid arthritis (RA) is a systemic, inflammatory, autoimmune disorder with progressive articular damage that may result in lifelong disability. Although major strides in understanding the disease have been made, the pathogenesis of RA has not yet been fully elucidated. Early treatment can prevent severe disability and lead to remarkable patient benefits, although a lack of therapeutic efficiency in a considerable number of patients remains problematic. MicroRNAs (miRNAs) are small, non-coding RNAs that, depending upon base pairing to messenger RNA (mRNA), mediate mRNA cleavage, translational repression or mRNA destabilization. As fine tuning regulators of gene expression, miRNAs are involved in crucial cellular processes and their dysregulation has been described in many cell types in different diseases. In body fluids, miRNAs are present in microvesicles or incorporated into complexes with Argonaute 2 (Ago2) or high-density lipoproteins and show high stability. Therefore, they are of interest as potential biomarkers of disease in daily diagnostic applications. Targeting miRNAs by gain or loss of function approaches have brought therapeutic effects in various animal models. Over the past several years it has become clear that alterations exist in the expression of miRNAs in patients with RA. Increasing numbers of studies have shown that dysregulation of miRNAs in peripheral blood mononuclear cells or isolated T lymphocytes, in synovial tissue and synovial fibroblasts that are considered key effector cells in joint destruction, contributes to inflammation, degradation of extracellular matrix and invasive behaviour of resident cells. Thereby, miRNAs maintain the pathophysiological process typical of RA. The aim of the current review is to discuss the available evidence linking the expression of miRNAs to inflammatory and immune response in RA and their potential as biomarkers and the novel targets for treatment in patients with RA.
21909945 Serum level of oxidative stress marker is dramatically low in patients with rheumatoid art 2012 Dec Regarding the pathobiology of rheumatoid arthritis, oxidative stress induced by reactive oxygen species is an important mechanism that underlies destructive and proliferative synovitis. Abundant amounts of reactive oxygen species have been detected in the synovial fluid of inflamed rheumatoid joints. It is reported that drugs that block tumor necrosis factor-α reduce the oxidative stress marker levels in patients with rheumatoid arthritis. In this study, we measured reactive oxygen species using a free radical analytical system in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, tumor necrosis factor-α-blocking drugs (infliximab, etanercept), and an interleukin-6-blocking drug (tocilizumab). The serum level of oxidative stress was drastically low in patients with rheumatoid arthritis treated with tocilizumab, suggesting that interleukin-6 blocking therapy reduces not only joint damage, but also vascular degeneration in patients with rheumatoid arthritis. We believe that such a drastic effect would reduce the incidence of cardiovascular events and mortality in patients with rheumatoid arthritis.
21210348 Rheumatoid nodule and combined pulmonary carcinoma: topographic correlations; a case repor 2011 Mar An association between rheumatoid arthritis (RA) and malignancies has been ascertained and patients with RA appear to be at higher risk of lymphoma and lung cancer. The higher risk of the latter malignancy may be related to rheumatoid interstitial lung disease and immunosuppressive therapies. Herein we illustrate the case of a 59-year-old male smoker affected by RA and treated with cortisone, methotrexate and TNF-α antagonists, who underwent right lower lobectomy for a nodular lesion. On microscopic examination, the lesion consisted of two distinct areas: a central area of fibrinoid necrosis, bordered by histiocytes in a palisaded arrangement, lymphocytes and a 0.4 cm thick peripheral area constituted by a combined small cell anaplastic carcinoma, adenocarcinoma and squamous cell carcinoma. The combination of three histotypes is very rare in such a small tumour. In our case, it may be hypothesized that synchronous, heterogeneous mutations occurred in different type of committed cells or in stem cells, due to the production of cytokines by RA nodule histiocytes and lymphocytes, which are contiguous to the carcinomatous area. Since few studies have evaluated the topographic correlation between tumors and rheumatoid lung lesions, further morphological and molecular studies are needed to clarify this association and the pathogenetic relationship between RA and cancer of the lung.
22577892 Vaccination under TNF blockade - less effective, but worthwhile. 2012 May 14 Only after biological response modifiers have become available have we begun to understand some of the complex functions of TNF in the human immune system. TNF is clearly essential for fighting intracellular pathogens, but probably not essential for fighting tumors. TNF influence on the humoral immune response, in contrast, has been more complicated to decipher, since TNF blockade is associated with both autoantibody formation and (somewhat) reduced responses to vaccination. Novel data now show that TNF is good for the humoral immune response. Vaccinations still work, however, and should be strongly recommended.
21649536 Abatacept: a biologic immune modulator for rheumatoid arthritis. 2011 Aug INTRODUCTION: Abatacept is a biologic drug that belongs to the class of T-cell co-stimulation modulators and is used for the treatment of rheumatoid arthritis (RA). AREAS COVERED: This article covers major randomized clinical trials and meta-analyses concerning abatacept in the treatment of RA, as identified in a Pubmed search. Scientific meeting abstracts describing long-term extension data of the identified trials are also included. Efficacy outcomes and the safety profile are the focus of this evaluation. EXPERT OPINION: Abatacept in combination with methotrexate (MTX) or other synthetic disease-modifying anti-rheumatic drugs (DMARD) has been proven effective for the treatment of RA in different groups of patients: with early RA and no prior exposure to DMARD; with DMARD-resistant RA; and with RA not responding to TNF-α-blocking agents. Significant reductions of disease activity are achieved, with 1-year remission rates reaching up to 41% of DMARD-naïve patients with early RA receiving a combination of abatacept plus MTX. Abatacept treatment has been shown to improve function and quality of life and to suppress radiographic progression. No major safety issues have emerged during clinical trials and long-term extensions. Therefore, abatacept is a drug with a favorable efficacy and safety profile, which may offer substantial benefits to RA patients.
21421646 Long-term patterns of depression and associations with health and function in a panel stud 2011 May Long-term patterns of depression, and associations with health and function were examined among 1115 individuals with rheumatoid arthritis, using 18 years of panel data, summarized in 9653 interviews. Depression was defined by scores on the Geriatric Depression Scale (6 or above). Participants were classified, using cluster analysis, into three distinct patterns of depression over repeated assessments: nondepressed (65.8%), intermittent (25.2%), and chronic (9.0%). GEE analyses assessed outcomes over time as a function of patterns of depression; controlling for demographic and clinical factors. Results indicated that patterns of depression had significant adverse effects on health and function over time.
22749821 Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. 2012 Nov Rheumatoid arthritis (RA) is a chronic inflammatory disorder that primarily involves the joints. Accurate and frequent assessment of RA disease activity is critical to optimal treatment planning. A novel algorithm has been developed to determine a multi-biomarker disease activity (MBDA) score based upon measurement of the concentrations of 12 serum biomarkers in multiplex format. Biomarker assays from several different platforms were used in feasibility studies to identify biomarkers of potential significance. These assays were adapted to a multiplex platform for training and validation of the algorithm. In this study, the analytical performance of the underlying biomarker assays and the MBDA score was evaluated. Quantification of 12 biomarkers was performed with multiplexed sandwich immunoassays in three panels. Biomarker-specific capture antibodies were bound to specific locations in each well; detection antibodies were labeled with electrochemiluminescent tags. Data were acquired with a Sector Imager 6000, and analyte concentrations were determined. Parallelism, dynamic range, cross-reactivity, and precision were established for each biomarker as well as for the MBDA score. Interference by serum proteins, heterophilic antibodies, and common RA therapies was also assessed. The individual biomarker assays had 3-4 orders of magnitude dynamic ranges, with good reproducibility across time, operators, and reagent lots; the MBDA score had a median coefficient of variation of <2% across the score range. Cross-reactivity as well as interference by serum rheumatoid factor (RF), human anti-mouse antibodies (HAMA), or common RA therapies, including disease-modifying antirheumatic drugs and biologics, was minimal. The same MBDA score was observed in different subjects despite having different biomarker profiles, supporting prior literature reports that multiple pathways contribute to RA.
21800407 The suitability of yoga as a potential therapeutic intervention for rheumatoid arthritis: 2011 Dec OBJECTIVES: The aim of this study was to explore the views of patients with rheumatoid arthritis (RA) regarding the suitability of yoga as a potential therapeutic intervention in the management of RA. METHODS: Twenty-two participants with RA were recruited from outpatient clinics at a regional hospital in New Zealand and divided into four focus groups. Heterogeneity between groups in terms of age, gender, duration of RA and functional ability provided opinions from a cross-section of RA patients. Transcripts were analysed using thematic analysis, with four themes predominating. RESULTS: Firstly, participants described their experience of symptoms related to their RA in three independent but linked categories of physical, mental and social well-being. Secondly, participants perceived the management of their RA to be prescriptive, medicalized and failing to address their wider health concerns. Thirdly, participants perceived yoga as a safe, adaptable therapy that may allow self-management of their RA. However, there was some concern that functional limitations may inhibit ability to practise the physical aspects of yoga. Fourthly, requirements for a yoga intervention that would be feasible for people with RA were presented by participants. CONCLUSIONS: Patients with RA perceive a disparity between their personal experience of living with RA and their current medical management. Yoga is perceived as a potential therapy to address this disparity. Based on opinions expressed by participants, future research regarding a yoga intervention as an adjunctive therapy for managing RA should meet patients' views on feasibility and test outcome measures reflecting the domains of physical, mental and social well-being.
22098699 Primary care physicians' perspectives towards managing rheumatoid arthritis: room for impr 2011 INTRODUCTION: Many people with rheumatoid arthritis (RA) do not receive care from a rheumatologist. We surveyed primary care physicians (PCPs) to better understand their attitudes, knowledge, and practices regarding the optimal treatment of RA. METHODS: Randomly selected PCPs practicing in the US were surveyed. The survey encompassed their experience with RA, use of disease modifying anti-rheumatic drugs (DMARDs), and experience with rheumatology referrals. Logistic regression analyses described the responses and examined the correlation between physician variables and use of DMARDs. RESULTS: E-mail invitations were opened by 1, 103 PCPs and completed by 267 (25%). Most respondents were men (68%) in practice for over 10 years (64%) who reported 6 or more RA patients under their care in the last year (71%). The majority reported some RA training after medical school (59%), but only one-third felt very confident managing this condition. Most (81%) reported prescribing DMARDs, but 37% do not initiate them, with only 9% reporting being very confident starting a DMARD. In unadjusted analyses, several respondent characteristics were strongly associated with not prescribing DMARDs, but none was significant after adjustment. Almost half (44%) of PCPs noted that patients report difficulty getting appointments with rheumatologists. CONCLUSIONS: We found many PCPs are uncomfortable managing RA with DMARDs, despite common beliefs that their patients lack access to a rheumatologist. Lack of accessibility to rheumatologists and discomfort in prescribing DMARDs for patients with RA are potential barriers to optimal treatment.
22035432 TNF inhibitors for rheumatoid arthritis - a year in review. 2011 The identification of tumor necrosis factor-alpha (TNF-a) as an important mediator in the pathogenesis of rheumatoid arthritis (RA) led to the development of TNF inhibitors (TN- FIs), which has ushered in a revolution not only in therapies for RA, but other rheumatic diseases as well. Treatment strategies for RA will continue to evolve as new agents are developed and as new data become available. This article provides a summary of clinical studies with TNFIs conducted in RA patients and reported over the previous 18 months based on a PubMed search using the terms TNFIs (with their individual generic names) and RA.
21858583 Clinical and radiological results of GSB III total elbow arthroplasty in patients with rhe 2012 Apr Total elbow arthroplasty (TEA) with the GSB III prosthesis was performed in 32 patients (36 elbows) with rheumatoid arthritis between 2001 and 2009. At final follow-up, 31 patients (35 TEAs) were available for clinical and radiological evaluation. The mean follow-up period was 6.3 (2.0-10.3) years, with a minimum follow-up of 2 years. The mean Mayo elbow performance score was significantly improved from 48 points preoperatively to 83 points at final follow-up. The radiographic loosening rate was 14.3% for humeral components and 5.7% for ulnar components. There were 4 cases of intraoperative fracture and 1 case of humeral shaft fracture at 4 months after surgery. The rates for loosening and fracture were relatively low when compared with those in other studies of linked TEA. There were 2 cases of ulnar nerve palsy, but there was no deep infection or triceps disruption. The clinical results of TEA using the GSB III prosthesis in patients with rheumatoid arthritis were found to be satisfactory.
23078913 Interest of modelling in rheumatoid arthritis. 2012 Jul Such as prospective studies can provide evidence-based information for clinicians and regulatory agencies, modelling studies provide useful information when experimental studies are to complex, too long, or too expensive to carry out. If modelling has been widely used in pharmacokinetics, it is in the field of pharmacoeconomics that numerous models have been published in recent years, including models relevant to the management of rheumatoid arthritis (RA). The most common modelling techniques published in RA are decision trees and Markov models which are used to perform cost-effectiveness and cost-utility analyses using real or simulated populations. This paper reviews the main types of modelling techniques used in pharmacoeconomic studies with the aim of clarifying their interest and limitations for the clinicians. Generating such evidence is highly relevant to assisting clinical recommendations and reimbursement decisions towards enabling the optimal management of RA and reducing its overall clinical and economic burden, for the benefits of patients and health systems.
21607710 Induction of clinical remission with adalimumab-methotrexate combination therapy in a pati 2011 Dec The patient described here is a 49-year-old woman who had hepatitis C virus (HCV) infection and rheumatoid arthritis (RA). Her RA had been successfully managed with methotrexate for about 10 years. After a sustained virological response was achieved with interferon therapy, treatment with adalimumab was instituted. This resulted in a rapid and sustained remission that lasted for more than a year, without HCV reactivation. The results in this case suggest that a sequential strategy, with initial HCV clearance followed by the targeting of remission with biologics, may be a favorable option in patients with RA and concomitant HCV infection.
22956596 The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthrit 2013 Jul PURPOSE: To determine the sensitivity to change of the US7 score among RA patients under various therapies and to analyze the effect of each therapeutic option over 1 year. To estimate predictors for development of destructive bone changes. METHODS: Musculoskeletal ultrasound (US7 score), DAS28, CRP and ESR were performed in 432 RA patients at baseline and after 3, 6 and 12 months. The cohort was divided into four sub-groups: first-line DMARDs (Group 1; 27.3%), therapy switch: DMARDs to second DMARDs (Group 2; 25.0%), first-line biologic after DMARDs therapy (Group 3; 35.4%) and therapy change from biologic to second biologic (Group 4; 12.3%). RESULTS: The US7 synovitis and tenosynovitis sum scores in grey-scale (GSUS) and power Doppler ultrasound (PDUS) as well as ESR, CRP decreased significantly (p<0.05) after 12 months in group 1 to 3. Group 1+2 also illustrated a significant change of DAS28 after 1 year (p<0.001). Only in Group 4, the US7 erosion sum score decreased significantly from 4.3 to 3.6 (p=0.008) after 1 year. Predictors capable of forecasting US erosions after one year were: higher score of US7 synovitis (p<0.001), of US7 erosions in GSUS (p<0.001), as well as of DAS28 (p<0.001) at baseline. CONCLUSIONS: The comparable developments of the US7 score with clinical and laboratory data illustrates its potential to reflect therapeutic response. Therefore, the novel US7 score is sensitive to change. Patients who switched from one biologic to another exhibited a significant decline in erosions after 12 months, while the erosions scores in the other groups were stable.
23002057 Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis. 2013 Dec Rheumatoid arthritis (RA) is a chronic inflammatory disease preferentially affecting the joints and leading, if untreated, to progressive joint damage and disability. Cytokines, a group of small inducible proteins, which act as intercellular messengers, are key regulators of the inflammation that characterizes RA. They can be classified into pro-inflammatory and anti-inflammatory groups. Numerous cytokines have been implicated in the regulation of RA with complex up and down regulatory interactions. This paper considers a two-variable model for the interactions between pro-inflammatory and anti-inflammatory cytokines, and demonstrates that mathematical modelling may be used to investigate the involvement of cytokines in the disease process. The model displays a range of possible behaviours, such as bistability and oscillations, which are strongly reminiscent of the behaviour of RA e.g. genetic susceptibility and remitting-relapsing disease. We also show that the dose regimen as well as the dose level are important factors in RA treatments.