Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
15142257 Chemokine blockade: a new era in the treatment of rheumatoid arthritis? 2004 Blockade of chemokines or chemokine receptors is emerging as a new potential treatment for various immune-mediated conditions. This review focuses on the therapeutic potential in rheumatoid arthritis, based on studies in animal models and patients. Several knockout models as well as in vivo use of chemokine antagonists are discussed. Review of these data suggests that this approach might lead to novel therapeutic strategies in rheumatoid arthritis and other chronic inflammatory disorders.
12922967 Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates 2003 Sep OBJECTIVES: To characterise RA in a sample of Spanish patients by estimating mean clinical activity, functional ability, and radiological damage, and current and cumulative prevalence of extra-articular manifestations. METHODS: Cross sectional analysis of a cohort of patients with RA randomly selected from the clinical databases of 34 centres. Standard definitions and measurements were used, and radiographs read centrally. Estimates and confidence intervals were adjusted to sampling. RESULTS: Data were available for 788 patients. Extra-articular RA was present in 285 (36.2%) patients. Cumulative prevalence and 95% confidence intervals of extra-articular manifestations were estimated: nodules 24.5% (21.5 to 27.5), Sjögren's syndrome 17.0% (14.4 to 19.6), atlantoaxial subluxation 12.1% (9.8 to 14.4), carpal tunnel syndrome 10.7% (7.8 to 13.6), interstitial lung disease 3.7% (2.4 to 5.0), serositis 2.5% (1.4 to 3.5), eye disease 2.5% (1.1 to 3.9), vasculitis 1.3% (0.5 to 2.1), amyloidosis 0.6% (0.1 to 1.2), and Felty's syndrome 0.3% (<0.6). Mean (SD) activity/progression indexes were: DAS28-3 3.4 (1.2), HAQ 1.6 (0.4), Larsen score 54.7 (26.4). Less than 5% of the patients were in remission. 205 (72%) patients were receiving disease modifying antirheumatic drugs (DMARDs). CONCLUSION: Spanish patients with RA ever seen by a rheumatologist have, on average, a moderate degree of activity, despite widespread use of DMARDs. Measures of the degree of progression do not show a benign disease. The proportion of extra-articular manifestations in Spanish patients with RA is similar to that found in other Mediterranean populations, and lower than that reported in Anglo Saxon countries.
12508408 The Stanford Health Assessment Questionnaire: a review of its history, issues, progress, a 2003 Jan Over the last 2 decades, assessment of patient health status has undergone a dramatic paradigm shift, evolving from a predominant reliance on biochemical and physical measurements to an emphasis upon health outcomes based on the patient's personal appreciation of their illness. The Health Assessment Questionnaire (HAQ), published in 1980, was among the first instruments based on patient centered dimensions. The HAQ was designed to represent a model of patient oriented outcome assessment and has played a major role in diverse areas such as prediction of successful aging, inversion of the therapeutic pyramid in rheumatoid arthritis (RA), quantification of nonsteroidal antiinflammatory drug gastropathy, development of risk factor models for osteoarthrosis, and examination of mortality risks in RA. The HAQ has established itself as a valuable, effective, and sensitive tool for measurement of health status. It has increased the credibility and use of validated self-report measurement techniques as a quantifiable set of hard data endpoints and has contributed to a new appreciation of outcome assessment. We review the development, content, and dissemination of the HAQ and provide reference sources for its uses, translations, and validations. We discuss contemporary issues regarding outcome assessment instruments relative to the HAQ's identity and utility. These include: (1) the issue of labeling instruments as generic versus disease-specific; (2) floor and ceiling effects in scales such as "disability"; (3) distances between values on scales; and (4) the continuing introduction of new measurement instruments and their potential effects.
12969323 Molecular targets in immune-mediated diseases: the case of tumour necrosis factor and rheu 2003 Oct Rheumatoid arthritis is a common autoimmune condition in which, for unknown reasons, synovial joints become the target of a sustained immune response. For many years, rheumatoid arthritis was in the 'too hard basket' in terms of understanding disease mechanisms and providing rational therapy. This has changed dramatically over the last 10 years and rheumatoid arthritis is now at the forefront of biotechnology. In this review, we outline one of the most exciting recent developments, namely antagonists of the cytokine TNF. The preclinical evaluation of TNF in animal models of rheumatoid arthritis, and subsequent clinical trials of TNF inhibitors in patients, provides insight into the 'bench to bedside' paradigm. We therefore briefly review rheumatoid arthritis, animal models of rheumatoid arthritis, the biology of TNF, the pivotal clinical trials of TNF antagonists and the emerging data on side-effects. Tumour necrosis factor inhibitors in rheumatoid arthritis represent the first attempt to achieve sustained blockade of a single cytokine in a human disease. Whilst this approach has been even more successful than might have been predicted, we suggest it is only the beginning of what has become a new therapeutic era.
12966617 Wegener's granulomatosis in patients with rheumatoid arthritis. 2003 Sep OBJECTIVE: To describe 2 cases of coexisting rheumatoid arthritis (RA) and Wegener's granulomatosis (WG), and to summarize the clinical and serological data for all 6 patients reported in the English literature since 1966. METHODS: Medline review over a 35-year period (1966-2002) revealed 4 reported cases of RA associated with WG. Patients were diagnosed based on symptoms, radiographic changes, bronchoalveolar lavage fluid analysis, hematuria, serology, and biopsy. We describe 2 additional cases of WG developing in Caucasian women with RA. These are the first reported patients to possess positive antineutrophil cytoplasmic antibodies (ANCA) and autoantibodies to proteinase 3 (PR3). RESULTS: All 6 cases of coexisting RA and WG were female. The diagnosis of RA preceded WG diagnosis in all cases; mean age at RA onset was 43.7 +/- 15.0 years, duration of RA prior to WG diagnosis 7.9 +/- 9.1 years. Clinical findings included erosive articular disease on radiographs (n = 4; 67%), positive rheumatoid factor (n = 6; 100%), upper respiratory involvement (n = 5; 83%), lower respiratory signs (n = 4; 67%), renal involvement (n = 2; 33%), and positive ANCA (n = 2/3; 67%). Five patients were treated with corticosteroids and cyclophosphamide, with clinical improvement. CONCLUSION: Although rare, WG may develop in patients with preexisting RA and may present with end-organ involvement.
12833650 Inhibitors of p38 mitogen-activated protein kinase for the treatment of rheumatoid arthrit 2003 May The p38 mitogen-activated protein kinase pathway is involved in a number of cellular processes critical to the development of rheumatoid arthritis. The activation and infiltration of leukocytes as well as the production of inflammatory cytokines are p38-dependent processes. In addition, p38 regulates the differentiation of osteoclasts, which are directly involved in bone loss. Numerous inhibitors of p38 have demonstrated efficacy in animal models of arthritic disease and at least two p38 inhibitors are currently in phase II clinical trials for rheumatoid arthritis. Several other p38 inhibitors are currently undergoing phase I clinical trials.
15302339 Stem cell transplantation for autoimmune disorders. Rheumatoid arthritis. 2004 Jun Haematopoietic stem cell transplantation (HSCT) is now being investigated as a potential therapy for patients with severe refractory rheumatoid arthritis unresponsive to conventional therapies, including tumour necrosis factor-alpha blockade. Pilot studies and an analysis of worldwide cases included in the European Group for Blood and Marrow Transplantation/Autologous Blood and Marrow Transplant Registry registry have enabled the progression of the technique. HSCT is well tolerated in patients with rheumatoid arthritis, and there has been no transplant-related mortality. Although HSCT is not a cure, an improved response to previously ineffective therapies is often seen. Further research is, however, required, and this procedure is still considered appropriate only for those patients for whom there is no reasonable therapeutic alternative. This paper reviews all the previous data relating to HSCT in rheumatoid arthritis, outlines the current stand and discusses future protocol options and research.
15593110 Managing arthritis and employment: making arthritis-related work changes as a means of ada 2004 Dec 15 OBJECTIVE: To understand arthritis-related workplace changes, including occasional work loss and changes to the type and hours of work, and the factors associated with them using theories of adaptation and behavior change as a framework. METHODS: Participants were 492 employed individuals with rheumatoid arthritis or osteoarthritis. They completed an interview-administered, structured questionnaire assessing demographic, workplace, and psychosocial variables, as well as such work transitions as changes to the hours, type, and nature of work. Hypotheses were examined using multiple linear regression. RESULTS: Seventy percent of respondents made at least 1 work change. Younger participants and those with greater workplace activity limitations reported more changes. Work changes were associated with greater depression. A hypothesized 3-way interaction among people's perceptions of their capacity, their future job expectations, and whether they had told their employer about their arthritis was significant. CONCLUSION: This study extends arthritis employment research by examining a range of work changes. It highlights the dynamic interplay among arthritis, workplace, and psychosocial variables to understand adaptation to arthritis disability.
15077290 Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressi 2004 Apr OBJECTIVE: To categorize radiographic joint damage as progressive or nonprogressive in individuals with rheumatoid arthritis (RA) participating in clinical studies. METHODS: Using the total Sharp radiographic damage score, erosion score, and joint space narrowing (JSN) score for 751 serial films of the hand/wrist and forefoot obtained from 190 patients with early RA during 6-60 months of followup (mean 31 months), various threshold values for progression of joint damage were evaluated singly and in various combinations. For each patient, the progression rate was estimated from the linear regression line for all available radiographic time points. After preliminary screening, 23 candidate definitions were tested to select a definition that discriminated well between radiographic progression and radiographic nonprogression. RESULTS: The definition selected describes radiographic nonprogression in individual patients as an increase of < or =0.1 in the standardized response mean of the trimmed population (the central 95% of patients) for > or =5 of 6 change measures (erosion scores and JSN scores for the fingers, wrists, and feet). Using this definition, 59% of the 190 patients with early RA were defined as having nonprogressive radiographic damage. Moreover, 95% of 95 patients with progression of the total Sharp score at or below the median and 24% of 95 patients with progression of the total Sharp score above the median were defined as having nonprogressive joint damage (chi(2) = 98, P < 0.0001), as were 97% of patients in the lowest quintile of total Sharp score progression rates and none of the patients in the highest progression quintile. Patients defined as nonprogressors had significantly lower baseline levels of C-reactive protein and lower erythrocyte sedimentation rates compared with patients defined as progressors, and those patients in the nonprogressive joint damage group more frequently had American College of Rheumatology 20% and 50% improvement criteria responses, "good" improvements (decrease of > or =1.2) in the Disease Activity Score, and > or =50% decreases in the swollen joint counts during the first 2 years of followup. CONCLUSION: RA joint damage in an observational cohort can be classified as progressive or nonprogressive with the use of a composite definition. Validation and/or refinement of this definition is needed by utilizing the data from controlled clinical trials that compare placebo with active treatment.
14673965 Effects of concurrent strength and endurance training in women with early or longstanding 2003 Dec 15 OBJECTIVE: To investigate the effects of a 21-week concurrent strength and endurance training protocol on physical fitness profile in women with early or longstanding rheumatoid arthritis (RA) compared with healthy subjects. METHODS: Twenty-three female patients with RA volunteered for the study. Twelve had early RA and eleven had longstanding RA. Twelve healthy women served as controls. Maximal strength of different muscle groups was measured by dynamometers, walking speed with light cells, and vertical squat jump on the force platform to mirror explosive force. Maximal oxygen uptake was measured by gas analyzer. Six training sessions (3 strength training and 3 endurance training) were carried out in a 2-week period for 21 weeks. RESULTS: The training led to large gains in maximal strength both in women with RA and in healthy women (P < 0.043-0.001). The strength gains were accompanied by increases in walking speed (P < 0.034-0.001) and vertical squat jump (P < 0.034-0.001). Significant improvements also occurred in maximal aerobic capacity in all groups (P < 0.023-0.014). CONCLUSIONS: Both early and longstanding RA patients with stable disease can safely improve all characteristics of their physical fitness profile using a progressive concurrent strength and endurance training protocol.
12392337 Cervical myelopathy and rheumatoid arthritis: a retrospective analysis of management. 2002 Sep BACKGROUND: Although a number of recent studies have described the outcome of surgical treatment of patients with rheumatoid cervical myelopathy, few have reported outcome in those unable to have surgery. We sought to examine the outcome in this group of patients regardless of surgical intervention. DESIGN: Retrospective and descriptive. SETTING: Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne, UK. METHODS: Retrospective review of case notes of 40 patients (31 females, 9 males) with rheumatoid cervical myelopathy diagnosed 1988-1997. RESULTS: The mean age was 64 years (range 36-80 years). The mean duration of rheumatoid arthritis (RA) before the development of myelopathy was 21 years (range 5-44 years). The common impairments were paraesthesia in the arms, neck pain and weakness. Twenty-five patients (60%) were deemed fit for surgery (group I). Twenty-two patients successfully had operative treatment and the others refused. Twelve of the 15 patients who reported pain preoperatively obtained pain relief. Six of the 11 patients who were nonambulant (Ranawat class IIIB) were able to walk postoperatively. There were two deaths within six months (9% mortality) after primary surgery due to pneumonia and sepsis. Seven of the 15 patients managed conservatively (group II) because of coexisting medical complications died within six months of presentation (47% mortality). CONCLUSIONS: The study confirms the overall benefit of surgical intervention in those who are medically stable. Following surgery some functional improvement may occur even in patients with severe myelopathy.
12515284 Is pregnancy a model how we should control some autoimmune diseases? 2002 Aug Pregnancy and parturition are the physiological conditions that affect the course and severity of numerous autoimmune diseases. If genotype might be primarily considered as a determinant of whether or not autoimmunity develops, clinical heterogeneity of the disease might arise from the interaction of the genotype and the environment. Numerous external factors with extremely important immunoregulatory properties, including hormones, affect an in vivo open complex immune system. The further investigation of the role of neuroendocrine-immunological network, including a pregnancy-associated immunomodulation, as much as the role of "causative" or "trigger" agents, may allow the rational basis of new alternative treatment of numerous autoimmune diseases.
15638049 Ultrasonography detection of early bone erosions in the metacarpophalangeal joints of pati 2004 Nov OBJECTIVE: To compare ultrasonography (US) and magnetic resonance imaging (MRI) in their capability to detect bone erosions in early-advanced rheumatoid arthritis, where no erosion was evident on conventional radiography (X-ray). METHODS: Metacarpophalangeal (MCP), radiocarpal and ulnocarpal joints of 13 patients with rheumatoid arthritis, with bone erosion that was not detected by conventional X-ray, were examined by US and MRI. Ten controls underwent examination of the same joints by US. RESULTS: None of the controls showed bone erosions at US examination. No significant difference between US and MRI in detecting bone erosion was observed in wrist joints, whereas a significantly higher number of erosions was detected by US in MCP joints. CONCLUSION: US is at least as sensitive as MRI in detecting bone erosions in MCP and wrist joints. Since US examination is a more easily available and less expensive procedure than MRI, our findings justify its use as a diagnostic tool for early arthritis. In addition US may also be utilized in the follow up of patients with an established diagnosis of inflammatory arthritis.
14969049 The role of ultrasonography and magnetic resonance imaging in early rheumatoid arthritis. 2003 Sep Advances in ultrasound (US) and magnetic resonance imaging (MRI) techniques have provided new methods for evaluating early rheumatoid arthritis (RA). Their diagnostic properties in terms of detecting primary pathology of RA (i.e., erosions, bone changes, synovitis, tenosynovitis, and effusion) are reviewed. High-resolution US plays a significant role in therapeutic and diagnostic procedures. MRI also assists in the understanding of RA pathogenesis and joint mechanics.
15223658 Chronic clonal proliferative disease of gamma-delta (gammadelta) T-cells in a patient with 2004 Sep Normal gammadelta T-lymphocytes have the morphology of large granular lymphocytes (LGL) and, as the LGL of alphabeta T-cells, they express pan-T antigens, NK-associated antigens and the cytotoxic molecules, perforin and granzime B. In this report we describe an unusual patient with rheumatoid arthritis and neutropenia who has a chronic gammadelta T-cell proliferation with a chronic, indolent clinical course and atypical lymphocytes, lacking the classical LGL morphology, not expressing NK-associated antigens, and not expressing perforin or granzyme B. In spite of the atypical morphological features of the clonal cells, which were suggestive of a more malignant process, the patient has been followed for 4 years without aggressive therapy. It is important to recognize this entity and to distinguish it from other gammadelta T proliferations such as the hepatosplenic gammadelta T-cell lymphoma.
15380045 Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone de 2004 This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.
12635942 Shoulder joint involvement in patients with newly diagnosed rheumatoid arthritis. Prevalen 2003 OBJECTIVE: To estimate the prevalence of reduced function, compared to normative values, and tenderness in the shoulder in patients with newly diagnosed rheumatoid arthritis (RA), and to investigate associated factors. METHODS: Eighty consecutive patients with RA, participating in a prospective study of early rheumatoid arthritis, were examined and assessed within one year of the onset of symptoms. RESULTS: The prevalence of tenderness from any of the shoulder joints was 50%, while 30% had decreased shoulder function, compared with age matched controls, in at least one shoulder. Both tender shoulder joints and decreased shoulder function were related to higher age and more severe disease, reflected by disability (HAQ) and the patient's assessment of pain and global disease activity. CONCLUSION: The shoulder girdle is involved early and often in rheumatoid arthritis and involvement is associated with a substantially more severe disease status. The study suggests that the shoulder should be given attention in patients with newly diagnosed rheumatoid arthritis, and that both tenderness and shoulder function should be evaluated.
15077266 History of affective disorder and the experience of fatigue in rheumatoid arthritis. 2004 Apr 15 OBJECTIVE: To evaluate how a prior affective disorder (major depression or generalized anxiety disorder) affects current fatigue among individuals with rheumatoid arthritis (RA). To determine whether that relationship is mediated by self-efficacy expectations. METHODS: Forty-eight RA patients with a prior affective disorder and 74 without a history of affective disorder completed a mailed questionnaire that included the Multidimensional Assessment of Fatigue and indicators of neuroticism and self efficacy. RESULTS: RA patients with a history of affective disorder reported higher levels of fatigue than those with no previous affective disturbance. Controlling for neuroticism and self efficacy, affective disorder history continued to predict current fatigue. Mediational analyses revealed both direct and indirect effects (via self efficacy) of history of affective disorder on the experience of fatigue in RA. CONCLUSION: History of affective disorder independently predicts higher levels of fatigue in RA patients, and self efficacy plays a mediating role in this relationship.
11777359 Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical 2002 Jan 1 BACKGROUND: Oral glucocorticoids combined with disease-modifying antirheumatic drugs are beneficial and retard radiologic joint damage in rheumatoid arthritis. OBJECTIVE: To investigate the clinical efficacy, disease-modifying properties, and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis. DESIGN: 2-year randomized, double-blind, placebo-controlled clinical trial. SETTING: 2 outpatient rheumatology clinics. PATIENTS: 81 patients with early active rheumatoid arthritis who had not been treated with disease-modifying antirheumatic drugs. INTERVENTION: 41 patients were assigned to 10 mg of oral prednisone per day, and 40 were assigned to placebo. Nonsteroidal anti-inflammatory drugs were allowed in both groups. After 6 months, sulfasalazine (2 g/d) could be prescribed as rescue medication. MEASUREMENTS: Clinical variables were assessed at baseline and every 3 months; radiologic studies were performed every 6 months. Adverse effects were documented every 3 months. RESULTS: In the first 6 months, the prednisone group showed more clinical improvement than the placebo group. This effect was not seen after 6 months except in grip strength and the 28-joint score for tenderness. Use of additional therapies was significantly less common in the prednisone group, particularly in the first 6 months. More than 65% of those who completed the study were not taking sulfasalazine. After month 6, radiologic scores showed significantly less progression in the prednisone group than in the placebo group. No clinically relevant adverse effects were observed, except for a higher incidence of osteoporotic fractures in the prednisone group. CONCLUSIONS: Prednisone, 10 mg/d, provides clinical benefit, particularly in the first 6 months, and substantially inhibits progression of radiologic joint damage in patients with early active rheumatoid arthritis and no previous treatment with disease-modifying antirheumatic drugs. Because of their limited disease-modifying effects, glucocorticoids should be combined with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.
15501186 Quantification of radiological damage in inflammatory arthritis: rheumatoid arthritis, pso 2004 Dec Quantification of radiological damage in inflammatory arthritis is important. It has proven its value in clinical trials, but its use in clinical practice is becoming more important as well. Scoring methods for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are available. These differ in the joints and features assessed. This results in differences in the scoring range, but also in the method of performance. The various methods for the three diseases are detailed in this chapter. Most information is available for rheumatoid and for this disease the relationship between radiological damage and long-term outcome is summarised.