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ID PMID Title PublicationDate abstract
16980210 Treating very early rheumatoid arthritis. 2006 Oct Rheumatoid arthritis (RA) is common and leads to joint damage due to persistent synovitis. The persistence of inflammation is maintained by hyperplastic stromal tissue, which drives the accumulation of leukocytes in the synovium. Aggressive treatment after the first 3-4 months of symptoms, with either disease modifying anti-rheumatic drugs or anti-tumor necrosis factor (TNF)-alpha therapy, reduces the rate of disease progression. However, it rarely switches off disease such that remission can be maintained without the continued need for immunosuppressive therapy. There is increasing evidence that the first few months after symptom onset represent a pathologically distinct phase of disease. This very early phase may translate into a therapeutic window of opportunity during which it may be possible to permanently switch off the disease process. The rationale for, and approaches to, treatment within this very early window are discussed.
18974408 Information and participation in decision-making about treatment: a qualitative study of t 2008 Nov OBJECTIVES: To elicit the perceptions and preferences of patients with rheumatoid arthritis regarding information and participation in treatment decision-making. To analyse the patients' narratives on the background of the ethical discourse on various approaches to treatment decision-making. DESIGN: In-depth interviews with themes identified using principles of grounded theory. PARTICIPANTS: 22 patients with long-standing rheumatoid arthritis. MAIN OUTCOME MEASURES: Qualitative data on patients' perceptions and preferences regarding information and participation in decision-making about treatment. RESULTS: Decision-making about treatment has been described by the patients as a process consisting of different stages with shifting loci of control and responsibility. Patients initially received one treatment recommendation and were not aware of alternative treatment options. Those participants in this study who wanted information about negative effects of a treatment cited "interest in one's own health" and the potential "use of information" as reasons for their preference. The physicians' expert knowledge and clinical experience regarding the effects of medication were cited as arguments by patients for a treatment recommendation. CONCLUSIONS: The patients' accounts of decision-making about treatment differ from models of physician-patient relationship that have been put forward in ethical discourse. These differences may be relevant with respect to the starting point of an ethical analysis of treatment decision-making. Patients' accounts with respect to a lack of information on treatment alternatives point to ethically relevant challenges regarding treatment decision-making in clinical practice.
18791056 Methods of deriving EULAR/ACR recommendations on reporting disease activity in clinical tr 2008 Oct OBJECTIVE: To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications. RESULTS: The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The "patient-reported symptom state" (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts. CONCLUSIONS: The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR.
17621798 [Current therapeutic strategy for rheumatoid arthritis]. 2006 Oct 19 The success of the treatment of rheumatoid arthritis depends primarily on early diagnosis. In most cases, basic therapy begins with methotrexate. Depending on the stage and course of the disease (radiographically detected early erosion and/or progression), basic immunosuppressive therapy can be combined or supplemented with cytokine antagonists. Furthermore, for specific indications, several alternative active substances (DMARD monotherapies) are available. Today the goal of therapy is always remission.
16876600 Long-term incidence of subaxial cervical spine instability following cervical arthrodesis 2006 Aug OBJECTIVE: Cervical spine deformities are well-known complications of RA. A 5- to 20-year follow-up of 51 consecutive rheumatoid patients who underwent posterior cervical arthrodesis is presented to evaluate the recurrence of instability and need for further surgery. METHODS: We conducted a retrospective review of the clinical features of 11 men and 40 women with an established diagnosis of RA and associated cervical deformities who underwent cervical spine surgery at the Mayo Clinic (Rochester, MN) between 1979 and 1990. Their mean age was 61 +/- 10 years (SD), and their duration of RA averaged 21 +/- 8.9 years (SD). There were 22 patients who presented with myelopathy, 7 with radiculopathy, and 22 with instability/neck pain. There were 33 patients with AAS, 2 with SMO process into the foramen magnum, 8 with SAS, and 8 with combinations of these. Preoperative reduction was followed by decompression and fusion using wiring techniques and autologous bone graft. Postoperative halo orthosis was provided for at least 3 months. The mean follow-up was 8.3 +/- 6 years (SD). RESULTS: There were 31 patients (61%) who underwent atlantoaxial arthrodesis, 17 patients (33%) who underwent subaxial, and 3 patients (6%) who underwent occipitocervical arthrodesis. During follow-up, 39% (13/33) of patients with AAS developed nonsymptomatic (6) or symptomatic/unstable (7) SASs subsequent to C1-C2 fusion. The latter 7 patients (21%) subsequently required extension of their arthrodesis. Adjacent segment disease was most common at the C3-C4 interspace after atlantoaxial fusion in 62% (8/13). Among the 8 patients who underwent isolated cervical fusion for SAS, 1 patient (1/8, 12%) developed adjacent instability after a fall and required extension of the previous fusion. No secondary procedure was required for the 6 patients initially stabilized by C1-(C6-T1) fusions for combinations of AAS + SAS. None of the patients initially treated by C1-C2 arthrodesis for AAS progressed to SMO. CONCLUSIONS: The incidence of subaxial instability in patients with rheumatoid disease who underwent cervical arthrodesis may be higher than previously reported, indicating the need for continued follow-up in these patients. Adjacent segment disease may be most common at the C3-C4 level following atlantoaxial fusion. Early stabilization of the C1-C2 complex in the patients with AAS may potentially prevent progression of SMO.
17715172 Cytokines in arthritis--the 'big numbers' move centre stage. 2008 Jan More than 20 yrs ago, T-helper lymphocytes were divided into Th1 and Th2 subsets on the basis of their cytokine production. The pro-inflammatory Th1 subset was considered predominant in inflammatory arthritis, but evidence for this notion was incomplete, and some called into question the role of helper T cells. The identification of a novel T cell subset, Th17 cells, which appears to be critical for several forms of autoimmune inflammation, including arthritis, requires a reconsideration of arthritis pathogenesis and the role of T cells. This review deals with several of the newly described ('big number') cytokines which are involved in the differentiation and action of Th17 cells, and pays particular attention to the pathogenesis of spondyloarthritis because of the implication of the same cytokine networks in psoriasis and inflammatory bowel disease. The role of dendritic cells as coordinators of T cell differentiation in response to pathogen-derived signals in also emphasized.
16358365 Patient, disease, and therapy-related factors that influence discontinuation of disease-mo 2006 Feb OBJECTIVE: A major challenge in management of rheumatoid arthritis (RA) is prediction of longterm response to disease-modifying antirheumatic drug (DMARD) treatment. Our objective was to identify the predictors of DMARD discontinuation in an incidence cohort of patients with RA followed continuously from their incidence date. METHODS: Members of a population-based incidence cohort of Rochester, Minnesota, residents aged > or = 18 years diagnosed with RA (by 1987 American College of Rheumatology criteria) from January 1, 1955, to January 1, 1995, were followed longitudinally through their complete medical records until January 1, 2001. Detailed drug exposure data were collected on all DMARD and glucocorticoid regimens. Subjects were considered exposed to a DMARD if duration of use was > or = 30 days. Time to discontinuation of DMARD was estimated using survival analysis techniques. Andersen-Gill models with multiple events per patient were used to assess the influence of demographics, calendar time, comorbidities, disease characteristics [disease duration, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), joint counts, radiographic changes, nodules, RA complications], and therapy characteristics (DMARD use, singly or in combination, glucocorticoid use, first or subsequent regimen, effect of previous therapy) on time from DMARD initiation to discontinuation. RESULTS: The study population comprised 345 DMARD-treated patients (73% female) with mean age of 53.1 years and mean followup 15.4 years. Median time taking any DMARD was 16.0 months for the first, and 17.9 months for all regimens. Methotrexate (MTX) had the longest time to discontinuation, with a median of 30.3 months without folate, and 61.7 months with folate supplementation. Among the various disease characteristics examined, only higher ESR at DMARD initiation was significantly associated with a shorter time taking DMARD [hazard ratio (HR) 1.05 per 10 mm/h increase, 95% CI 1.02, 1.08]. In multivariable Andersen-Gill models considering all DMARD regimens, hydroxychloroquine use (HR 0.77, 95% CI 0.64, 0.92) and MTX use (HR with folate 0.39, 95% CI 0.30, 0.51; HR without folate 0.51, 95% CI 0.39, 0.67) were significantly associated with longer time to DMARD discontinuation, whereas prior MTX use (HR 1.96, 95% CI 1.57, 2.45) was associated with shorter time to DMARD discontinuation, after adjusting for age, sex, calendar year, Charlson comorbidity index, disease duration, and ESR at DMARD initiation. Disease duration was negatively associated with time to DMARD discontinuation; each 10 year increase in disease duration corresponded to a 14% decrease in the risk of discontinuation (HR 0.86, 95% CI 0.75, 0.98). CONCLUSION: Longer RA disease duration does not appear to increase the risk of DMARD discontinuation. However, high disease activity (as assessed by ESR) is associated with a higher likelihood of discontinuing DMARD. MTX failure may identify a subgroup of patients who are less likely to respond to other DMARD and therefore could be considered as candidates for biological therapies.
18254021 Post-operative therapy for metacarpophalangeal arthroplasty. 2008 Jan 23 BACKGROUND: Metacarpophalangeal (MCP) arthroplasty with implants, which is the replacement of painful knuckle joints with artificial knuckle joints, has been performed for people with rheumatoid arthritis (RA) since the 1960s. The surgery is done because RA can cause damage of the knuckle joints making them unable to straighten out (flexion deformity) and causing them to lean over toward the small finger (flexion or ulnar deviation deformity). For eight to 12 weeks following surgery, patients wear hand splints and perform exercises to maintain and increase motion in the healing hand. Post-operative therapy regimes share common aims of encouraging MCP flexion and extension without the recurrence of flexion or ulnar deviation deformity. OBJECTIVES: To compare the effectiveness of post-operative therapy regimes for increasing hand function after MCP arthroplasty in adults with rheumatoid arthritis. SEARCH STRATEGY: The Cochrane Musculoskeletal Group Register, MEDLINE (January 1950 to August 2006), EMBASE (January 1993 to August 2006), CINAHL (January 1982 to August 2006), Digital Dissertations (January 1960 to August 2006), DARE (The Cochrane Library 2006, Issue 3), Current Contents Connect (January 1998 to August 2006), and AMED (January 1985 to August 2006) were searched for randomised controlled trials and controlled clinical trials using rheumatoid arthritis and hand as the search terms. The bibliographies of all trials identified by this strategy were also searched and primary authors were contacted for unpublished data and also clarification regarding study protocols. We performed handsearches of all relevant society conference proceedings and reference lists of retrieved articles. No language limits were applied, although searches were only relevant after the 1950s when MCP arthroplasty began to be performed. SELECTION CRITERIA: Randomised controlled trials and controlled clinical trials were accepted if they evaluated the efficacy of a post-operative therapy regime for MCP arthroplasty. DATA COLLECTION AND ANALYSIS: No data analyses were performed as only one controlled clinical trial was found. The data from that study are described. MAIN RESULTS: Our search only identified one controlled clinical trial involving 22 participants. The majority of the evidence for various splinting and exercise regimes consisted of case series and case studies. Results from the one (poor quality) trial suggest that the use of continuous passive motion is not effective in increasing motion or strength after MCP arthroplasty. AUTHORS' CONCLUSIONS: Well-designed randomised controlled trials which compare the efficacy of different therapeutic splinting programmes following MCP arthroplasty are required. At this time, the results of one study (silver level evidence) suggest that continuous passive motion alone is not recommended for increasing motion or strength after MCP arthroplasty.
18843428 Effectiveness of a night-time hand positioning splint in rheumatoid arthritis: a randomize 2008 Oct OBJECTIVE: To evaluate the effectiveness of a night-time hand positioning splint in patients with rheumatoid arthritis. DESIGN: Randomized controlled trial. METHODS: Fifty patients with rheumatoid arthritis were divided randomly into 2 groups. The study group used a night-time splint starting at baseline, while the control group used the splint only during evaluations. All patients attended evaluations wearing their splints, so that the assessor remained blinded to patient allocation. The splints used in the control group were stored in a cabinet between assessments. Participants were evaluated at baseline, 45 and 90 days, using the visual analogue scale for pain; the Jamar dynamometer for grip strength; a pinch gauge for pinch strength; a Health Assessment Questionnaire for function; the Disability of the Arm, Shoulder and Hand (DASH) questionnaire for upper limb disability and symptoms; and a Likert scale for patient satisfaction with treatment. RESULTS: The groups were homogenous for all parameters at baseline. Pain, Health Assessment Questionnaire score, DASH score, grip strength and pinch strength were significantly different between groups over time and satisfaction with the splint was reported as "better" and "much better" by most participants. CONCLUSION: The use of a night-time hand positioning splint reduces pain, improves grip and pinch strength, upper limb function and functional status in patients with rheumatoid arthritis.
18951353 [Dry cough, chest pain and difficult breathing in a patient with rheumatoid arthritis]. 2008 Oct 22 Pulmonary involvement is the most frequent extra-articular manifestation of rheumatoid arthritis. The occurrence of a chronic hydro-pneumo-thorax associated with pulmonary nodules is rare. Cavitation of the most superficial nodules and their rupture into the pleural cavity are most likely involved in this complication. The presence of broncho-pleural fistulae may be responsible for the persistence of the phenomenon in our patient.
17036505 [Difficulties in differential diagnosis of Sjögren's syndrome and systemic lupus erythema 2006 Sjögren's Syndrome (SS) is the second most common autoimmune disorder after rheumatoid arthritis (RA). It can be found as a lone condition (primary Sjögren's Syndrome) or may accompany other autoimmune rheumatic diseases (secondary Sjögren's Syndrome). Despite such frequent occurrence, accurate diagnosis of Sjögren Syndrome is difficult. These difficulties result from highly variable symptoms of SS as well as from common presence of other autoimmune disorders. In the following article authors present current knowledge concerning clinical symptoms, diagnostic methods and latest clinical guidelines on the diagnosis of SS. Differential diagnosis of SS and systemic lupus erythematosus (SLE) is also discussed.
16739068 Anti-arthritic activity of a lipophilic woad (Isatis tinctoria) extract. 2006 Jun A dichloromethane extract of Isatis tinctoria was tested in the adjuvant-induced arthritis model in rats. The extract (150 mg/kg p. o.) leads to a significant reduction of paw oedema. Radiographic, histological and clinical assessment confirmed reduced damage of cartilage and signs of inflammatory response in comparison to untreated control. No significant differences were observed in the tissular levels of cyclooxygenases 1 and -2, and of inducible nitric oxide synthase in Isatis treated and untreated animals. High dose treatment with Isatis extract for two weeks did not result in macroscopic lesions of the gastric mucosa.
16973114 Recent advances in the genetics of rheumatoid arthritis. 2006 Oct Recent progress in defining the role of genetic factors in rheumatoid arthritis (RA) has been remarkable. Anticyclic citrullinated peptide (anti-CCP) antibody-positive disease appears to be immunogenetically distinct from anti-CCP-negative disease, with the former subgroup primarily responsible for association and linkage with the HLA-DRB1 shared epitope (SE). There is preliminary evidence that non-HLA genes contribute differentially to anti-CCP-positive and negative disease. The phenotypic differences evident in anti-CCP-positive and negative disease suggest a need to reclassify RA based on the presence or absence of this autoantibody. Some recent work also suggests marked interactions between cigarette smoking, anti-CCP antibodies, and the SE, though these relationships may vary across populations. Lastly, a recent single nucleotide polymorphism-based genome-wide linkage analysis of multicase RA families revealed novel genomic regions that likely contain genes that predispose to RA or more specific phenotypes.
17984580 [Rheumatoid arthritis and interleukin-32]. 2007 Oct Inflammatory cytokine cascade plays a pivotal role in the pathogenesis of rheumatoid arthritis. Recently, a novel human cytokine, interleukin-32, was reported to induce TNF-alpha. Interleukin-32 is expressed mainly in lymphoid tissues and leukocytes, but also in stimulated epithelial cells and synovial fibroblasts. Although the interleukin-32 receptor has not been reported, interleukin-32 can induce other inflammatory cytokines, such as TNF-alpha, interleukin-1beta, and interleukin-6 from monocytes/macrophages in vitro and in vivo, and synergizes with signals from pattern-recognition receptors. Notably, in the inflamed synovial tissues from rheumatoid arthritis patients, interleukin-32 is prominently expressed and correlates with the severity of arthritis and the expression of other cytokines, including TNF-alpha and interleukin-1. In experimental mice models of arthritis, joint injection of interleukin-32 induces joint inflammation, and overexpression of interleukin-32beta in haematopoietic cells exacerbates collagen-induced arthritis. Herein, interleukin-32 plays an important role in the pathogenesis of rheumatoid arthritis.
17406499 Collagen antibody-induced arthritis. 2006 Collagen antibody-induced arthritis (CAIA) is a simple mouse model of rheumatoid arthritis that can be used to address questions of pathogenic mechanisms and to screen candidate therapeutic agents. Arthritis is stimulated by the administration of a cocktail of monoclonal antibodies that are directed to conserved auto-antigenic epitopes in collagen type II, followed by endotoxin. The antibody-induced arthritis model offers several key advantages over the classic collagen-induced arthritis (CIA) model. These include rapid disease onset, high uptake rate, synchronicity, and the capacity to use genetically modified mice, such as transgenics and knockouts. This protocol takes 1-2 weeks to be completed.
17172717 Collagen-induced arthritis in mice: a major role for tumor necrosis factor-alpha. 2007 Collagen-induced arthritis is the most widely used animal model for the evaluation of novel therapeutic strategies for rheumatoid arthritis. The disease is induced by immunization of genetically susceptible strains of mice or rats with type II collagen in adjuvant. Susceptibility to collagen-induced arthritis is associated with major histocompatibility complex (MHC) class II genes, although non-MHC genes also play a role. Both B- and T-lymphocytes are important in the pathogenesis of collagen-induced arthritis, with the peak of the T-cell response occurring around the time of disease onset. Histopathological assessment of the joints of animals with collagen-induced arthritis reveal a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, the formation of an erosive pannus, cartilage degradation, and fibrosis. As in human rheumatoid arthritis, a number of both pro- and anti-inflammatory cytokines are expressed in the joints of mice with collagen-induced arthritis, including tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta, IL-6, IL-1Ra, IL-10, and transforming growth factor beta. The use transgenic and knockout strains of mice, as well as biological inhibitors, have revealed important pathological roles for multiple cytokines. Of these, TNFalpha emerged as a valid therapeutic target for rheumatoid arthritis and this led to the setting up of clinical trials of anti-TNFalpha antibody therapy. Three anti-TNFalpha biologics(infliximab, etanercept, and adalimumab) are now approved for use and TNFalpha blockade therefore represents an important advance in our ability to treat rheumatoid arthritis.
17515956 Molecular profile of peripheral blood mononuclear cells from patients with rheumatoid arth 2007 Jan Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. Currently, diagnosis of RA may take several weeks, and factors used to predict a poor prognosis are not always reliable. Gene expression in RA may consist of a unique signature. Gene expression analysis has been applied to synovial tissue to define molecularly distinct forms of RA; however, expression analysis of tissue taken from a synovial joint is invasive and clinically impractical. Recent studies have demonstrated that unique gene expression changes can be identified in peripheral blood mononuclear cells (PBMCs) from patients with cancer, multiple sclerosis, and lupus. To identify RA disease-related genes, we performed a global gene expression analysis. RNA from PBMCs of 9 RA patients and 13 normal volunteers was analyzed on an oligonucleotide array. Compared with normal PBMCs, 330 transcripts were differentially expressed in RA. The differentially regulated genes belong to diverse functional classes and include genes involved in calcium binding, chaperones, cytokines, transcription, translation, signal transduction, extracellular matrix, integral to plasma membrane, integral to intracellular membrane, mitochondrial, ribosomal, structural, enzymes, and proteases. A k-nearest neighbor analysis identified 29 transcripts that were preferentially expressed in RA. Ten genes with increased expression in RA PBMCs compared with controls mapped to a RA susceptibility locus, 6p21.3. These results suggest that analysis of RA PBMCs at the molecular level may provide a set of candidate genes that could yield an easily accessible gene signature to aid in early diagnosis and treatment.
18828888 Are biologics more effective than classical disease-modifying antirheumatic drugs? 2008 Major achievements have been reached in the treatment of rheumatoid arthritis during past decades due to the recognition of methotrexate as an anchor drug for treatment of rheumatoid arthritis, due to the notion of a treatment window of opportunity in patients with recent-onset rheumatoid arthritis necessitating early aggressive therapy, due to the development of biologics and due to remission as a treatment target. Most biologics have a much faster onset of action than synthetic disease-modifying anti-rheumatic drugs, but presently there is no convincing evidence that biologic drugs have a superior clinical efficacy in comparison with the synthetic drugs. Biologics are, however, accompanied by less radiological deterioration.
20103932 Inflammaging (inflammation + aging): A driving force for human aging based on an evolution 2008 Dec Aging, and especially human aging, can be explained by the emerging concept of parainflammation-driven inflammaging, i.e. a combination of inflammation and aging. Inflammaging posits that aging either physiologically or pathologically can be driven by the pro-inflammatory cytokines and substances produced by the innate immune system. Animals must maintain homeostasis as they age despite incessant attack from both intrinsic and extrinsic stimuli/antigens. These potentially harmful pro-inflammatory signals at a later stage of life may act antagonistically to the beneficial role they had in an earlier stage of life, like serving as developmental engines for body system formation. The concept of inflammaging is based on an antagonistic pleiotropy theory programmed during evolution. Clinical trials including caloric restriction, sirtuin activators, and p38 MAPK inhibitors against both pathological aging such as metabolic syndrome, diabetes mellitus, rheumatoid arthritis, and Werner syndrome and physiological aging have been proposed.
16897114 The changes in monosaccharide composition of immunoglobulin G in the course of rheumatoid 2007 May The objective of this study was to determine whether galactosylation of immunoglobulin G (IgG) in patients with rheumatoid arthritis (RA) correlates with severity and duration of illness. Serum IgG glycosylation from 50 patients with RA in comparison with 30 healthy controls was analyzed. IgG from sera was isolated and monosaccharide composition was determined by means of gas chromatography. Ratio of galactose to mannose content was calculated. Patients were divided into groups according to three different criteria: disease duration, severity of RA (disease activity score index), and radiological degree of advancement of illness according to Steinbrocker. In patients with RA, significant decrease (p<0,01) of galactose ratio was observed in comparison with healthy control. In patients with long duration of RA (more than 15 years), significant decrease of galactose (p<0.05) ratio in comparison with patients who have had arthritis for less then 5 years was observed. For the group of patients with severe RA, we found reduction of galactose (p<0.001) ratio vs the group of patients in remission. For those patients who had radiological stage IV according to Steinbrocker, IgG galactose (p<0.01) content per oligosaccharide chain were also more decreased than in those patients who had stage I RA. Decreased galactosylation and of IgG in RA was observed. The lack of this carbohydrate component of IgG correlates with severity and duration of RA and could be used in monitoring the progression in early arthritis.