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ID PMID Title PublicationDate abstract
31569873 [Thyroid hormone antibodies in rheumatoid arthritis]. 2009 Feb 15 The goal of the study was to investigate thyroid functional activity in rheumatoid arthritis (RA) and to identify the specific features of the generation of thyroid hormone antibodies in RA patients depending on the activity of the disease. Seventy-five patients with RA (61 (81.4%) females and 14(18.6%) males; mean age 54.1±11.6years) were examined. Physical examination and measurements of the level of thyroid hormones (free T4 and free TJ and the number of their antibodies were made. Thirty healthy individuals were examined as controls. The sera from RA patients showed antibodies to T4 and T3 in 45 and 39% of cases. There was a rise in thyroxine levels and T4 antibody concentrations with the higher activity of RA. Along with the routine clinical and laboratory parameters, the values of T3 and T4 antibodies may be used as an additional tool to characterize the activity of RA genesis.
21794739 [Epigenetic therapies, a step beyond biologics for rheumatoid arthritis]. 2010 Nov Over the last decade, the management of rheumatoid arthritis has evolved as a result of both the understanding of disease-related processes and the availability of the necessary high-throughput technology to provide patients with molecule-based therapies. New therapies allow the classification of patients into subsets as regards clinical response, at the same time adding to our knowledge of rheumatoid arthritis pathogenesis. New generations of molecules will likely soon be ready for "a la carte" treatment of patients. A promising field of research is epigenetics. Epigenetic regulatory mechanisms switch on and off the transcription of specific genes in individual cells. Acting as observers on non-adequate gene expression, these mechanisms yield protection against the development of tumours. The major achievement of epigenetic therapies could be their selective action on cells with altered epigenetic programs, and it is our challenge to recognize these alterations among patients with rheumatoid arthritis. Although safety concerns may arise, epigenetic drugs will likely be used to treat autoimmune diseases.
27789995 Effects of low-dose tacrolimus therapy in combination with methotrexate in patients with m 2010 The aim of the present clinical trial was to determine the efficacy and safety of low-dose administration of tacrolimus in combination with methotrexate (MTX) in rheumatoid arthritis (RA) patients with an insufficient clinical response to MTX alone. Eleven patients with active RA, despite treatment with MTX, were enrolled and given tacrolimus in combination with MTX for 24 weeks. The primary endpoint was the assessment of clinical improvement using the European League against Rheumatism criteria. Administration of tacrolimus to RA patients with an insufficient response to MTX produced significant improvement in the Disease Activity Score 28 after 8-24 weeks. In addition, after 24 weeks, 50% and 25% of patients had achieved moderate and good responses, respectively, and there were significant reductions in the Modified Health Assessment Questionnaire, the rheumatoid factor and serum matrix metalloproteinase-3 levels. The present preliminary study suggests that low-dose tacrolimus in combination with MTX is well tolerated and provides both clinical and economic benefits.
27789981 Long-term use of adalimumab in the treatment of rheumatic diseases. 2009 Adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor-alpha (TNFα), has been evaluated in various randomized placebo-controlled trials in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis. In the short time frame of these trials adalimumab has been shown to be effective in reducing disease activity, slowing radiographic disease progression and improving patients' quality of life, while at the same time demonstrating an acceptable safety profile. Furthermore, release of adalimumab on the market, prospective observational studies, as well as open-label extensions of the original double-blind trials have provided experience and data about the long-term efficacy and safety of the drug. Initial effectiveness, in terms of reducing disease activity, is sustained, while in most cases patients treated with adalimumab experienced a slower radiographic progression and consequently less disability and improved health-related quality-of-life outcomes. Moreover, long-standing treatment of thousands of patients with adalimumab outside the controlled context of clinical trials was not related to new safety signals, with the most common adverse events being respiratory infections. The most common serious adverse events seem to be tuberculosis reactivation, while a putative association with malignant lymphoma development is not yet proven. Besides, both of these adverse reactions pertain to the whole TNFα blocker group. In conclusion, adalimumab is a safe and effective option for the treatment of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis.
26000107 Role of regulatory T cells in rheumatoid arthritis: facts and hypothesis. 2010 May Regulatory T cells (Treg) are a CD4(+) lymphocyte subset involved in self-tolerance and autoimmunity prevention. There is evidence for a phenotypic and/or functional impairment of this cell subset during the natural history of several chronic autoimmune/inflammatory diseases, including rheumatoid arthritis (RA). Although the intracellular transcription factor FoxP3 is thought to be the master regulator of Treg cell function, a number of other molecules expressed on the cell surface have been proposed for the identification of Treg cells. This is important in order to favour their possible selective isolation and in the development of new therapeutic strategies. In the present paper, available data on phenotypic and functional characterization of Treg cells in both peripheral blood and synovial fluid from RA patients are reviewed and their possible pathogenic role in triggering and perpetuating rheumatoid joint inflammation is discussed.
22347233 Seroprevalence of Acanthamoeba Antibodies in Rheumatoid Arthritis Patients by IFAT, Tehran 2010 Mar BACKGROUND: This preliminary study was conducted to discriminate the prevalence of Acanthamoeba antibodies in rheumatoid arthritis (RA) patients and healthy controls to analyze the correlation between these two groups. METHODS: From October 2006 to August 2007 a total of 121 serum samples from RA patients attending the Rheumatolgy Department at Shariati Hospital in Tehran were obtained and stored at -20°C until using by indirect fluorescent-antibody test (IFAT). RA was diagnosed according to the American Collage of Rheumatology classification criteria. The organism used in this study was isolated from various water resources in Tehran, Iran cultured axenically and then went on a PCR assay based on 18S rRNA to identify the genus Acanthomoeba. Indirect immunofluorescence antibody (IFA) staining of serum samples was carried out to detect anti Acanthomoeba antibodies. RESULTS: In culture, out of 22 samples, 13(59%) were grown in xenic but only two in axenic medium. PCR amplified a 904bp fragment, specific for Acanthamoeba. Of examined serum samples, Acanthamoeba antibodies were present in 70 (57.8%) and 52 (41.2%), respectively. The highest titer of antibodies (1:320) was detected in one patient with RA. CONCLUSION: Our study supports the hypothesis that some parasitic microorganisms can involve and contribute toward the development of rheumatoid syndromes.
24179373 Methotrexate-induced acute leukemia: report of three cases and review of the literature. 2009 For many years, methotrexate has been used in the treatment of certain chronic medical disorders e.g. rheumatoid arthritis and psoriasis as well as a number of malignant disorders e.g. acute lymphoblastic leukemia, certain types of lymphoma and breast carcinoma. Its use has been associated with various systemic toxicities and complications. The association between methotrexate therapy and the development of lymphoma and pseudolymphoma is well established. In patients treated with methotrexate, the development of leukemia has been attributed to either the primary disorder e.g. rheumatoid arthritis or to other drugs used concomitantly e.g. cyclophosphamide. Reported here are two patients with rheumatoid arthritis and one patient with psoriasis treated with low dose methotrexate for variable periods of time. Two of these patients developed acute myeloid leukemia on myelodysplastic syndrome background, while the third patient developed pre-B acute lymphoblastic leukemia that expressed few myeloid markers and had a positive philadelphia chromosome. To our knowledge, these are the first reported cases of methotrexate-induced acute leukemia.
21808685 Multiple pelvic insufficiency fractures in rheumatoid patients with mutilating changes. 2009 Oct 10 Multiple insufficiency fractures occurred in two patients with mutilating rheumatoid arthritis (RA), leading to substantial disabilities. Both patients received long-term oral glucocorticoid therapy and underwent multiple lower-extremity surgeries such as total hip arthroplasty (THA) or Total knee arthroplasty (TKA). The multiple fractures were located in the pelvis and lumbosacral region. Fractures in both patients were treated conservatively. Although bony union and resumption of activities were achieved in one patient, the other patient was not able to resume ambulation. For RA patients with combined risk factors for insufficiency fractures, aggressive preventive intervention and careful clinical assessment for early detection and management are warranted.
20131246 Effectiveness of rituximab treatment in primary Sjögren's syndrome: a randomized, double- 2010 Apr OBJECTIVE: To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sjögren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. METHODS: Patients with active primary SS, as determined by the revised American-European Consensus Group criteria, and a rate of stimulated whole saliva secretion of > or =0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. RESULTS: Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean +/- SD age of the patients receiving rituximab was 43 +/- 11 years and the disease duration was 63 +/- 50 months, while patients in the placebo group were age 43 +/- 17 years and had a disease duration of 67 +/- 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness-like disease. CONCLUSION: These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS.
29783543 Translational strategies to implement personalized medicine: rheumatoid arthritis examples 2009 Jul Advances in the molecular definition of disease, biomarker technologies and informatics have brought us to the threshold of a new way to individualize treatment for patients - personalized medicine. However, while the clinical translation of drug metabolism and cancer-related genomics data has resulted in accepted individualized treatment paradigms, this has not occurred as frequently or efficiently for patients with common chronic diseases such as rheumatoid arthritis. This gap between the rapidly increasing amount of disease-related genomic information and its clinical translation can be addressed through the creation and testing of personalized medicine treatment hypotheses using the same strategies that translational medicine scientists utilize to achieve proof-of-concept for drugs with novel targets. This is illustrated with three testable personalized medicine hypotheses for rheumatoid arthritis where known genetic markers in patients can potentially be used to select the most appropriate treatments and dose. Incentives resulting from changes in government and regulatory agency policies, investments in sample and data repositories, acceptance of new economic models by pharmaceutical companies and third party payers as well as more training, research support and academic opportunities for translational medicine scientists are all needed to speed up the implementation of personalized medicine for patients with rheumatoid arthritis and other common chronic diseases.
27789983 Update on the use of rituximab for intractable rheumatoid arthritis. 2009 It has been 3 years since rituximab, a mouse x human chimeric anti-CD20 monoclonal antibody that selectively depleted B cells, was approved by the FDA for the treatment of moderate to severe rheumatoid arthritis (RA) with an inadequate response to anti-TNF therapies. Since approval rituximab has become a part of standard treatment, and additional data have become available on long-term efficacy and safety both from clinical trials and from post-marketing surveillance. In open long-term follow-up from clinical trials, patients treated with multiple courses of rituximab continued to respond in terms of signs and symptoms, and damage assessed radiographically was significantly inhibited. Moreover, the rate of serious infectious events was not increased as the number of courses increased. However, because of case reports of progressive multifocal leukoencephalopathy in patients treated with rituximab for non-malignant conditions, a black box warning has been added. Studies on the immunologic correlates of response to rituximab treatment including B cell subsets in peripheral blood and synovial biopsies are providing clues into how rituximab works for autoimmune disease. However, at this time we are not able to explain why some patients do not respond and cannot predict who will respond. Future challenges for the further development of rituximab for intractable RA will be discussed.
22131727 Clinical efficacy of Rasona Pinda in the management of Amavata (rheumatoid arthritis). 2010 Jul In the present clinical study, 63 patients of Amavata were registered from the Kayachikitsa out patient department/indoor patient department (OPD/IPD) of Sir Sunder Lal Hospital (Indian Medicine Wing), IMS, BHU, Varanasi-5. In group I (Rasona Pinda), 27 patients completed the study of a total of 33patients registered in the group (six patients dropped out mid-therapy). In group II (control group), 23 patients completed all three follow-ups out of 30 patients (there were seven dropouts in mid-therapy). In group I, complete remission in 29.6%, major improvement in 59.3% and minor improvement in change font so as to appear 11.1% were observed. In group II, complete remission in 13%, major improvement in 21.7%, minor improvement in 39.1% and unchanged in 26.9% of the patients were observed.
19727885 Effects of the Sri Lankan medicinal plant, Salacia reticulata, in rheumatoid arthritis. 2010 Mar Salacia reticulata is a native plant of Sri Lanka. In the traditional medicine of Sri Lanka and India, Salacia reticulata bark is considered orally effective in the treatment of rheumatism, gonorrhea, skin disease and diabetes. We have investigated, both in vivo and in vitro, whether the leaf of Salacia reticulata (SRL) can ameliorate collagen antibody-induced arthritis (CAIA) in mice as the rheumatoid arthritis (RA) model. The mice were fed a lard containing chow diet (AIN-93G) or the same diet containing 1% (w/w) SRL powder. All mice were bred for 23 days. On day 7 or 14 after LPS injection, mice were killed, and tissue and blood samples were collected. Histological analysis was performed, and serum levels of inflammatory mediators and the mRNA levels of inflammation-related genes and osteoclast-related genes were measured. SRL treatment ameliorated the rapid initial paw swelling, inflammatory cells infiltration, skeletal tissues damage, osteoclast activation and the mRNA levels for osteoclast-related genes compared with the CAIA mice. However, the serum and mRNA levels of inflammatory mediators did not differ between the CAIA mice and the SRL-treated mice. SRL might reduce the inflammatory cells induction and skeletal tissue degradation by CAIA by the regulating osteoclastogenesis.
23555393 Acute palmer digital artery occlusion treated using endoscopic ablation of the thoracic sy 2010 Acute occlusion of the digital arteries frequently causes painful infarction requiring digital amputation. We describe a 55-year-old male patient who presented with acute onset of digital ischemia with impending gangrene on the right hand. Because angiography revealed bypass surgery was not feasible, he underwent thoracoscopic sympathectomy (TS) one week after onset of the symptom, which resulted in rapid pain resolution. He was diagnosed, thereafter, with malignant rheumatoid arthritis and methotrexate was administered. Postoperative angiography revealed that the occluded digital artery had become recanalized. Timely TS is therefore a treatment of choice for acute digital ischemia.
21927605 Microsomal prostaglandin e synthase-1 in rheumatic diseases. 2010 Microsomal prostaglandin E synthase-1 (mPGES-1) is a well-recognized target for the development of novel anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases and other inflammatory conditions. In this review, we focus on mPGES-1 in rheumatic diseases with the aim to cover the most recent advances in the understanding of mPGES-1 in rheumatoid arthritis, osteoarthritis, and inflammatory myopathies. Novel findings regarding regulation of mPGES-1 cell expression as well as enzyme inhibitors are also summarized.
21701623 Efficacy, tolerability and safety of biologic therapy in rheumatoid disease: patient consi 2010 Rheumatoid arthritis (RA) is a systemic inflammatory disease in which chronic inflammation leads to joint destruction and extra-articular complications. Early and effective inhibition of inflammation is critical in order to prevent the progressive joint damage that occurs rapidly after onset of the disease. In the past, treatment for this purpose was limited to conventional disease-modifying antirheumatic drugs (DMARDs), which were often suboptimal. Within the last decade however, the development of biologic therapies, targeted against cytokines and cells involved in the inflammatory process, has revolutionized the management of RA. Disease remission is now an achievable goal in newly diagnosed patients. Since the advent of the first tumor necrosis factor-α inhibitor in 1999, other biologics have proved necessary as individuals respond to varying degrees with different therapies. Several are now available for the treatment of patients with RA that remains active despite DMARD treatment. This article reviews the evidence, over the last decade, of the efficacy and safety of biologic therapies used in this context, and the recent clinical data supporting the use of biologic therapy earlier in the disease process as first-line therapy.
20216941 Nucleoprotein Diet Ameliorates Arthritis Symptoms in Mice Transgenic for Human T-Cell Leuk 2010 Mar Because rheumatoid arthritis (RA), an autoimmune disease, the patients often recognize side-effects due to the medication, alternative therapeutic strategies might potentially offer a clinical advantage. We evaluated the effect of nucleoprotein from salmon soft roe on animal model of arthritis. Mice transgenic for human T-cell leukemia virus type I (HTLV-1 Tg) were divided into three experimental groups and supplemented on either nucleoprotein-free (nonNP), or 0.6% or 1.2% nucleoprotein mixed (NP0.6 or NP1.2) diet for 3 months. The mice were evaluated arthritis by morphology, and measured with rheumatoid factor (RF). Moreover, macrophages and oxidative metabolites were assessed in the ankle and/or serum. Anti-oxidative potentials in nucleoprotein were determined with biological anti-oxidative potential (BAP) test, and electron spin resonance (ESR) analysis. NonNP-diet HTLV-1 Tg mice increased an arthritis symptoms and RF. The symptoms were ameliorated in NP-diet groups. Macrophages detected by F4/80 staining, and oxidative metabolites in the serum and/or joints were clearly decreased in 1.2% NP-diet HTLV-1 Tg mice. Nucleoprotein and DNA-nucleotide, but less protamine, had direct anti-oxidative potency with BAP test and/or ESR in vitro. These observations suggest that dietary nucleoprotein ameliorates arthritis symptoms in HTLV-1 Tg mice and offers hope as an alternative treatment for this debilitating medical condition.
23226040 Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and 2010 Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disorder of unknown etiology resulting in inflammation in the synovium, cartilage, and bone. Genetic factors play an important role in susceptibility to RA as the heritability of RA is between 50% and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Outside the major histocompatibility complex (MHC) region, six additional risk loci have been identified and validated including PTPN22, STAT4, PADI4, CTLA4, TNFAIP3-OLIG3, and TRAF1/C5. Genetic factors are also important in RA pharmacotherapy due to the gene-dependent activity of enzymes involved in the pharmacokinetics and/or pharmacodynamics of RA medications. Indeed, there is great variability in drug efficacy as well as adverse events associated with any anti-rheumatic therapy and genetics is thought to contribute significantly to this inter-individual variability in response. This review will summarize the genetic factors that have been implicated in the pathogenesis of RA, and how these determinants may factor into the potential pharmacogenetics of this disease. We will also review the therapeutic agents that are currently being utilized or presently being evaluated in the treatment of RA, along with potential pharmacogenetic markers that have been proposed for such medications.
20018075 Genome-wide association study of rheumatoid arthritis by a score test based on wavelet tra 2009 Dec 15 BACKGROUND: We have conducted a genome-wide association study on the Genetic Analysis Workshop (GAW) 16 rheumatoid arthritis data using a multilocus score test based on wavelet transform proposed recently by the authors. The wavelet-based test automatically adjusts for the amount of noise suppressed from the data. The power of the test is also increased by using the genetic information contained in the spatial ordering of single-nucleotide polymorphisms on a chromosome. RESULTS: After adjusting for the effect of population stratification, the test identified some previously discovered rheumatoid arthritis susceptibility loci (HLA-DRB1 and rs3761847) as well as some loci (rs2076530 and rs3130340) known to have association with sarcoidosis and bone mineral density. It was previously reported that patients with rheumatoid arthritis have elevated prevalence of sarcoidosis and have reduced bone mass. CONCLUSION: This new test provides a useful tool in genome-wide association studies.
21537466 Role of sphingosine kinase and sphingosine-1-phosphate in inflammatory arthritis. 2010 Nov 26 The importance of sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) in inflammation has been extensively demonstrated. As an intracellular second messenger, S1P plays an important role in calcium signaling and mobilization, and cell proliferation and survival. Activation of various plasma membrane receptors, such as the formyl methionyl leucyl phenylalanine receptor, C5a receptor, and tumor necrosis factor α receptor, leads to a rapid increase in intracellular S1P level via SphK stimulation. SphK and S1P are implicated in various chronic autoimmune conditions such as rheumatoid arthritis, primary Sjögren's syndrome, and inflammatory bowel disease. Recent studies have demonstrated the important role of SphK and S1P in the development of arthritis by regulating the pro-inflammatory responses. These novel pathways represent exciting potential therapeutic targets.