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ID PMID Title PublicationDate abstract
16979537 Problems encountered during anti-tumour necrosis factor therapy. 2006 Aug Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.
15708930 Immunopathology of psoriasis and psoriatic arthritis. 2005 Mar Psoriatic arthritis (PsA) is characterised by several unique clinical features that differentiate it from rheumatoid arthritis (RA). Attempts to identify immunopathological mechanisms, some shared with psoriasis, that underlie these differences from RA have been most challenging. Recent research studies, however, highlight novel findings in PsA at the molecular, cellular, and tissue levels that form the basis for a new understanding of this relatively common form of inflammatory arthritis. In particular, the availability of new, biological antitumour necrosis factor alpha therapies have allowed further insight into the immunopathology of psoriasis and PsA. This brief review focuses on immunohistological studies in psoriatic skin, PsA synovium, and bone to demonstrate how these data advance our knowledge of disease pathogenesis.
17181917 Epidemiology of rheumatoid arthritis, juvenile idiopathic arthritis and gout in two region 2006 Sep OBJECTIVE: To estimate the annual incidence and prevalence of rheumatoid arthritis (RA), juvenile arthritis (JIA) and gout in a population based study in two regions of the Czech Republic with total population of 186,000 inhabitants. METHODS: The study was conducted in the Town of Ceske Budejovice and district of Cheb in the Czech Republic (with a total population of 186,000 inhabitants) in the years 2002 and 2003. Incident cases were registered on condition that the definite diagnosis was confirmed according to existing classification criteria during the study period. Prevalence was studied on the basis of identification of established diagnosis from registers of patients of participating rheumatologists and other specialists. They were asked to report all living patients who had been diagnosed before 1st March 2002. Patients were only included in the study if their permanent address was in the selected study area. RESULTS: Overall, we found 48 incident and 947 prevalent cases of RA among adults (16+ years), 4 incident and 43 prevalent cases of JIA among children (less than 16 years old), and 64 incident and 425 prevalent cases of gout among adults (16+ years). The total annual incidence of RA was 31/100,000 in the adult population aged 16 years and more (95% CI 20 to 42/100,000). The prevalence of RA was 610/100,000 (95% CI 561 to 658/100,000) in the adult population. An annual incidence of gout in adults was 41/100,000 (95% CI 28 to 53/100,000). The prevalence of gout was 300/100,000 (95% CI 266 to 334/100,000). The annual incidence of JIA was 13/100,000 in children less than 16 years old (95%CI 1 to 20/100,000). The prevalence of JIA in children was 140/100,000 (95% CI 117 to 280/100,000). CONCLUSION: This study estimates the annual incidence and prevalence rates of RA, gout and JIA in the first population-based survey in the Czech Republic. The rates of RA and JIA compare well with figures reported from other countries; figures in gout seem to be lower than reported elsewhere.
20477615 Toll-like receptors: a new target in rheumatoid arthritis? 2006 Jul Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases. It is characterized by chronic inflammation of the joint leading to its destruction. Although the initiating cause remains elusive, environmental factors and genetic background are known to contribute to the etiology of RA. The role of Toll-like receptors (TLRs) in innate immunity and their ability to recognize microbial products has been well characterized. TLRs are able to recognize endogenous molecules released upon cell damage and necrosis, and are present in RA synovial fluid. Although it appears unlikely that a pathogen underlies the pathogenesis or progression of RA, the release of endogenous TLR ligands during inflammation may activate TLRs and perpetuate the disease. An increasing body of circumstantial evidence implicates TLR signaling in RA, although, at present, their involvement is not defined comprehensively. Targeting individual TLRs or their signaling transducers may provide a more specific therapy without global suppression of the immune system.
16112850 Neutrophil gene expression in rheumatoid arthritis. 2005 Oct There is now a growing awareness that infiltrating neutrophils play an important role in the molecular pathology of rheumatoid arthritis. In part, this arises from the fact that neutrophils have potent cytotoxic activity, but additionally from the fact that inflammatory neutrophils can generate a number of cytokines and chemokines that can have a direct influence on the progress of an inflammatory episode. Furthermore, the molecular properties of inflammatory neutrophils are quite different from those normally found in the circulation. For example, inflammatory neutrophils, but not blood neutrophils, can express cell surface receptors (such as MHC Class II molecules and FcgammaRI) that dramatically alter the way in which these cells can interact with ligands to modulate immune function. Cytokine/chemokine expression and surface expression of these novel cell surface receptors is dependent upon the neutrophil responding to local environmental factors to selectively up-regulate the expression of key cellular components via signalling pathways coupled to transcriptional activation. However, major changes in the expression levels of some proteins are also regulated by post-translational modifications that alter rates of proteolysis, and hence changes in the steady-state levels of these molecules.
15804667 Septic arthritis due to Salmonella enteritidis associated with infliximab use. 2005 A unique case of septic arthritis caused by Salmonella enteritidis in a patient receiving infliximab for rheumatoid arthritis is presented. Antimicrobial chemotherapy with surgical intervention was necessary for eradication of the infection. Physicians should be aware of rare manifestations of Salmonella infections associated with infliximab use, especially in endemic areas.
16382308 Pannus resolution after occipitocervical fusion in a non-rheumatoid atlanto-axial instabil 2006 Mar Periodontoid pseudotumor or pannus is considered to be an inflammatory mass most frequently associated with rheumatoid arthritis. Transoral resection of the pannus has been the treatment of choice for patients with associated myelopathy, followed in many instances by posterior stabilization. However, some authors have reported resolution of pannus associated with rheumatoid arthritis and other forms of chronic atlanto-axial instability only after posterior stabilization. We report a case of a 69-year-old man who presented with a rapidly progressing myelopathy due to a retro-odontoid mass produced by chronic atlanto-axial instability associated with an occipital assimilation of C1 and tight posterior fossa. An urgent posterior fossa craniectomy followed by occipitocervical fixation was performed. After surgery, the patient's clinical condition improved and 1 year after surgery was asymptomatic, walked without any help and had normal strength. Control MR showed complete resolution of the retro-odontoid pannus.
17151007 Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory 2007 May BACKGROUND: Rheumatoid arthritis is a chronic autoimmune disease of unknown aetiology characterised by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. AIM: To propose a new strategy for the treatment of arthritis based on the administration of cortistatin, a newly discovered neuropeptide with anti-inflammatory actions. METHODS: DBA/1J mice with collagen-induced arthritis were treated with cortistatin after the onset of disease, and the clinical score and joint histopathology were evaluated. Inflammatory response was determined by measuring the levels of various inflammatory mediators (cytokines and chemokines) in joints and serum. T helper cell type 1 (Th1)-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with collagen and by assaying the content of serum autoantibodies. RESULTS: Cortistatin treatment significantly reduced the severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of cortistatin was associated with a striking reduction in the two deleterious components of the disease-that is, the Th1-driven autoimmune and inflammatory responses. Cortistatin downregulated the production of various inflammatory cytokines and chemokines, decreased the antigen-specific Th1-cell expansion, and induced the production of regulatory cytokines, such as interleukin 10 and transforming growth factor beta1. Cortistatin exerted its effects on synovial cells through both somatostatin and ghrelin receptors, showing a higher effect than both peptides protecting against experimental arthritis. CONCLUSION: This work provides a powerful rationale for the assessment of the efficacy of cortistatin as a novel therapeutic approach to the treatment of rheumatoid arthritis.
16088875 Quantifying dynamic contrast-enhanced MRI of the knee in children with juvenile rheumatoid 2005 Sep Quantification of dynamic contrast-enhanced (DCE) MRI based on pharmacokinetic modeling requires specification of the arterial input function (AIF). A full representation of the plasma concentration data, including the initial rise and decay parts, considering the delay and dispersion of the bolus contrast is important. This work deals with modeling of DCE-MRI data from the knees of children with a history of juvenile rheumatoid arthritis (JRA) by using an AIF extracted from the signal enhancement data from the nearby popliteal artery. Three models for the AIFs were considered: a triexponential (AIF1), a gamma-variate plus a biexponential (AIF2), and a biexponential (AIF3). The pharmacokinetic parameters obtained from the model were Ktrans', kep, and V'p. The results from AIF1 and AIF2 showed no statistically significant difference. However, some statistically significant differences were seen with AIF3, particularly for parameters Ktrans' and V'p in the synovium (SNVM). These results suggest the importance of obtaining an appropriate AIF representation in pharmacokinetic modeling of JRA. Specifically, the initial rising part of the AIF should be incorporated for optimal pharmacokinetic modeling results. The pharmacokinetic parameters (mean+/-SD) derived from AIF1, using the average plasma concentration data, were as follows: SNVM Ktrans'(min-1)=0.52+/-0.34, kep(min-1)=0.71+/-0.39, and V'p=0.33+/-0.16, and for the distal femoral physis (DFP) Ktrans'(min-1)=1.83+/-1.78, kep(min-1)=2.65+/-1.80, and V'p=0.46+/-0.31. The pharmacokinetic parameters in the SNVM may be useful for investigating activity and therapeutic efficacy in studies of JRA. Longitudinal studies are necessary to find or demonstrate the parameter that is more sensitive to disease activity.
15568208 Prediction of ordinal outcomes when the association between predictors and outcome differs 2005 May 15 There are a number of regression models which are widely used to predict ordinal outcomes. The commonly used models assume that all predictor variables have a similar effect at all levels of the outcome variable. If this is not the case, for example if some variables predict susceptibility to a disease and others predict the severity of the disease, then a more complex model is required. One possibility is the multinomial logistic regression model, which assumes that the predictor variables have different effects at all levels of the outcome variable. An alternative is to use the stereotype family of regression models. A one-dimensional stereotype model makes the assumption that the effect of each predictor is the same at all outcome levels. However, it is possible to fit stereotype models with more than one dimension, up to a maximum of min(k-1, p) where k is the number of outcome categories and p is the number of predictor variables. A stereotype model of this maximum dimension is equivalent to a multinomial logistic regression model, in that it will produce the same predicted values and log-likelihood. If there are sufficient outcome levels and/or predictor variables, there may be a number of stereotype models of differing dimension. The method is illustrated with an example of prediction of damage to joints in rheumatoid arthritis.
16569257 Magnetic resonance imaging in psoriatic arthritis: a review of the literature. 2006 Psoriatic arthritis is a diverse condition that may be characterized by peripheral inflammatory arthritis, axial involvement, dactylitis and enthesitis. Magnetic resonance imaging (MRI) allows visualization of soft tissue, articular and entheseal lesions, and provides a unique picture of the disease process that cannot be gained using other imaging modalities. This review focuses on the literature on MRI in psoriatic arthritis published from 1996 to July 2005. The MRI features discussed include synovitis, tendonitis, dactylitis, bone oedema, bone erosions, soft tissue oedema, spondylitis/sacroiliitis and subclinical arthropathy. Comparisons have been drawn with the more extensive literature describing the MRI features of rheumatoid arthritis and ankylosing spondylitis.
15691217 TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. 2005 Psoriasis is a chronic inflammatory skin disease that can lead to significant physical and psychologic distress for patients. Psoriatic arthritis (PsA), originally thought to be quite a mild disorder, is now recognized as a progressive and destructive arthritis. To date, therapies for both these conditions have been non-specific and unable to maintain long-lasting remission. In addition, many of the current therapies have significant adverse effects, limiting their usefulness. However, elucidation of the pathogenesis of psoriasis and PsA at a molecular level and the development of selective biologic agents have led to an enormous expansion of the armamentarium available to psoriasis patients. Two agents (infliximab and etanercept) selectively block the role of the cytokine tumor necrosis factor (TNF)-alpha and have proved effective in clinical trials in the treatment of both the skin and the joint manifestations of psoriasis. A third anti-TNF alpha agent (adalimumab Humira) is licensed for the treatment of rheumatoid arthritis; however, no studies have been published to date on its use in PsA or psoriasis. It is known that TNF alpha is elevated in both the skin and synovium of psoriatic patients and the effectiveness of its blockade by these two agents in psoriasis and PsA confirms its role in their pathogenesis. Randomized, double-blind, placebo-controlled trials have been performed with both agents in the treatment of psoriasis and PsA; in the case of etanercept these have been to support US FDA approval for use in psoriatic arthropathy. These studies are supported by smaller cohorts in open-label studies and anecdotal reports in the literature. Anti-TNF alpha therapy has proved to have disease-reducing activity in PsA and psoriasis and appears to be well tolerated. These studies have generally featured small numbers of patients and, until a larger cohort of treated patients is available, vigilance must be exercised. A considerable body of post-marketing safety data exists on the use of infliximab in rheumatoid arthritis and Crohn disease and for etanercept in rheumatoid arthritis and PsA. Certain issues, particularly the risk of infection, have emerged as features of the use of these agents. It remains to be seen whether effects seen in other disease entities may be extrapolated to psoriatic patients. More long-term data and experience are needed to define the role of anti-TNF alpha agents in the management of psoriasis and PsA. In particular, more studies are required to elucidate the finer points of co-medication; in some studies both agents have been used with other medications but there have been no formal trials of various possible combinations.
28224585 Septic hip after a fractured neck of femur in a rheumatoid patient: A case report. 2005 Jan A 63-year-old rheumatoid patient presented with severe pain in her left hip without a preceding history of trauma. An initial clinical and radiological examination revealed no "obvious" abnormality and the patient was symptomatically treated. The patient presented again five weeks later as weightbearing became increasingly difficult due to worsening pain. Inflammatory markers were found to be elevated and a repeat radiological examination revealed a displaced ununited fracture of the neck of femur. Isotope imaging suggested increased activity around the hip. A formal arthrotomy revealed pus in the joint. She continued to deteriorate and subsequently died due to sepsis. Spontaneous fractures without any history of trauma have been described in patients with rheumatoid arthritis. The fracture haematoma serves as a good culture medium for micro-organisms in immuno-compromised rheumatoid patients. Any hip pain arising in a rheumatoid patient should be thoroughly investigated and a high index of suspicion is necessary for both sepsis and fracture. (Hip International 2005; 15: 59-61).
15834053 How to assess the impact of arthritis on the individual patient: the WHO ICF. 2005 May The ICF is not only a comprehensive and adequate framework for assessing the impact of arthritis on individual patients but also its impact on populations. The ICF framework and applications such as the ICF Core Sets for rheumatoid arthritis, osteoarthritis, osteoporosis, and low back pain are therefore likely to be used extensively not only in clinical practice but also in outcomes and rehabilitation research, education, health statistics, and regulation.
16738903 Psoriasis onset during infliximab treatment: description of two cases. 2006 Oct The authors describe two patients with no personal or family history of psoriasis who developed psoriatic lesions during infliximab treatment: a woman affected by seronegative rheumatoid arthritis and a man affected by ankylosing spondylitis.
16778596 Comparison of health-related quality of life between heterozygous women with Fabry disease 2006 Jun PURPOSE: Fabry disease is an X-linked lysosomal disorder due to mutations in the GLA gene. Manifestations of the disease are documented in hemizygous males. Recent studies have indicated that women with GLA mutations may report symptoms. The impact on their health-related quality of life is unclear. This study compares the quality of life of obligate heterozygotes to a historical healthy control population and to populations with multiple sclerosis and rheumatoid arthritis. METHODS: The RAND-36 and Fabry-disease specific questions were administered to study participants. Study subjects were obligate heterozygotes for mutations in GLA. Mean scores in each of the subscales from the RAND-36 were compared between study subjects and previously published data from the Women's Health Initiative and studies on multiple sclerosis and rheumatoid arthritis. RESULTS: Comparisons between 202 study participants and the Women's Health Initiative indicated that all eight subscale scores of the RAND-36 were significantly lower for women with Fabry disease (P < 0.0001). The mean scores of the study participants more closely resembled the mean scores of the participants in the multiple sclerosis and rheumatoid arthritis studies. CONCLUSION: Study participants reported clinically important effects on health-related quality of life. It is critical to develop management protocols for this population.
23424348 Emerging therapies offer new methods for treating rheumatoid arthritis. 2006 Apr The approvals of abatacept and rituximab have invigorated the already competitive market for biologic RA treatments. The new generation of RA therapies now reaching the market presents opportunities for patients - and challenges for payers.
16568212 WITHDRAWN: Validation of the Tunisian version of the rheumatoid arthritis quality of life 2006 Jul 13 Ahead of Print article withdrawn by publisher
15965816 [Importance of the new biologicals and cytokine antagonists in the treatment of juvenile i 2005 Jun Juvenile idiopathic arthritis is group of diseases of unknown aetiology characterised by the occurrence of chronic arthritis during childhood. Compared to adult onset rheumatoid arthritis, its course is more variable. Increasing knowledge of the inflammatory process as well as in molecular genetics and biotechnology has enable the production of new drugs, the biologicals. These are able to specifically block mechanisms of immune activation and thereby interfere with the inflammatory process. An increasing number of biologicals have been tried in clinical studies in adults suffering from rheumatoid arthritis, psoriasis or psoriasis arthritis and a couple of them were already licensed for treatment. Treatment of juvenile idiopathic arthritis by blockade of tumournecrosis-factor (TNF) using the soluble receptor Etanercept or the monoclonal antibodies Infliximab and Adalimumab showed comparable clinical efficacy. Blockade of TNF therefore already reached a certain place in the therapeutic algorythm for treatment of juvenile idiopathic arthritis. Currently, only Etanercept is licensed for treatment of active juvenile polyarthritis refractory to methotrexate. Studies using Infliximab and Adalimumab will be completed in the near future. However, antibodies blocking TNF may already be used in patients suffering from active uncontrolled chronic uveitis in whom visual impairment is threatening. TNF blockers may also be indicated in juvenile ankylosing spondylitis. The use of further biologicals, the interleukin-1 receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell membrane molecule CD28, remain experimental and should be preserved for clinical studies.
16892138 [Effect of multiple amino acid substitutions of collagen II 263-272 on collagen-induced ar 2006 Aug 18 OBJECTIVE: To evaluate the effect of multiple amino acid substitutions of C II 263-272 peptide on collagen-induced arthritis, and explore a therapeutic strategy of rheumatoid arthritis. METHODS: A panel of altered C II 263-272 peptides was synthesized with substitutions of TCR-contact residues of C II 263-272 with alanine. The competitive inhibition of APL to wild type C II 263-272 was analyzed by 3H incorporation assay. CIA model was induced by intradermal injection of bovine CII. Altered CII peptide was injected subcutaneously in different doses (1, 10, 100 microg, respectively, twice per week) after onset of CIA. The arthritis index, radiologic and histologic scores were recorded to evaluate the severity change of arthritis. Serum levels of IFN-gamma were examined by ELISA. RESULTS: Competitive inhibition to wild type C II 263-272 of the altered C II 263-272 peptides (APL1, APL2, APL3) was found in PBMC from RA patients. Among them, APL3 with substitution of residues 267(Q), 270(K) and 271(G) to A showed the most significant effect and thus was used in the treatment of CIA rats. We observed significantly reduced arthritis scores in CIA rats treated with 100 microg/dose of APL as compared with rats treated with PBS and peptide control. The mean radiographic and histologic scores was also markedly lower in APL-treated CIA rats than in PBS or peptide control-treated rats. On day 35 after immunization, the serum level of IFN-gamma in rats was examined and a significantly low level of serum IFN-gamma was found in APL-treated rats. CONCLUSION: C II 263-272 peptide with TCR-contact residues substitutions inhibited joint destruction in CIA rats and down-regulated IFN-gamma production, suggesting that altered CII peptide might be potentially therapeutic in rheumatoid arthritis.