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ID PMID Title PublicationDate abstract
12149042 Prevention or retardation of joint damage in rheumatoid arthritis: issues of definition, e 2002 This article discusses methodological concepts and challenges underlying the interpretation of changes in plain radiographs of the joints of patients with rheumatoid arthritis. A series of consensus conferences (OMERACT [Outcome Measures in Rheumatology]) has resulted in the formulation and execution of a research agenda to harmonise reading and interpretation of films. This is important in the light of the increasing evidence that drugs can impact on the progression of joint damage. In these conferences, methodological issues have been divided according to applicability tenets summarised in the OMERACT Filter of Truth, Discrimination, and Feasibility. To pass the Filter, a measure must measure what it is supposed to measure (Truth), must discriminate between clinically relevant states (Discrimination) and be feasible in terms of costs and interpretability. 'Truth' issues include the choice of joints, the view and other technical specifications of the radiograph, such as which abnormalities to score, the level of aggregation of the information, culminating in the choice of the scoring system. 'Discrimination' issues include reproducibility and sensitivity to change. The current research agenda includes items such as defining a criterion for 'no relevant progression', comparison between time ordered and randomly ordered reading, further comparison of methods and subscores, and methodology around missing values.
15552754 [Rheumatoid arthritis of the cervical spine: surgical management]. 2004 Sep Cervical spine involvement in patients suffering from rheumatoid arthritis significantly increases with time. This progression results in C1-C2 instability, vertical subluxation, subaxial spine subluxation or a combination of those three types of instability. It can remain asymptomatic or present with pain and/or neurological symptoms. Surgical treatment could be indicated in the presence of C1-C2 instability greater than 6 mm or even grater than 3 mm if there is associated vertical subluxation. Surgery can be associated with significant mortality and morbidity. In the presence of myelopathy surgical results can be particularly unfavourable with a mortality as high as 50%. It seems therefore important to proceed to surgical stabilisation quite early in order to prevent the onset of neurological involvement. Primary fusion extending to the upper thoracic spine should also be considered in selected patients in order to avoid the onset of caudal instability which can present with late development of progressive myelopathy.
12798660 Dietary n-3 fats as adjunctive therapy in a prototypic inflammatory disease: issues and ob 2003 Jun Eicosanoids derived from the n-6 fatty acid, arachidonic acid, and the cytokines interleukin-1beta and tumour necrosis factor-alpha are involved in the signs and symptoms of inflammatory joint disease, as well as the cartilage degradation seen in established rheumatoid arthritis (RA). Then n-3 fatty acids in fish and fish oil can inhibit production of both eicosanoid and cytokine inflammatory mediators and therefore, have the potential to modify RA pathology. Epidemiological studies suggest that fish intake may be preventive for RA and double-blind placebo-controlled studies demonstrate that dietary fish oil can alleviate the signs and symptoms of RA. The implementation of these findings will require among other things, a range of n-3 fat enriched foods, as well as physician awareness of the possibilities for dietary n-3 fat increases to be used as adjunctive therapy in RA.
12435166 Expanding role of biologic agents in rheumatoid arthritis. 2002 Nov Biologic agents are an important addition to the therapeutic armamentarium for rheumatoid arthritis (RA). Initially these drugs were reserved for use in patients with progressive RA who had an inadequate response to treatment with disease modifying antirheumatic drugs. The optimal role of biologics in the treatment of RA remains to be defined. Data from ongoing clinical trials will provide insight on when to most effectively administer these agents.
11840699 The genetics of the target tissue in rheumatoid arthritis. 2002 Feb The genetic mechanisms that are complementary in predisposing and then establishing disease are yet to be fully elucidated. During a lifetime, the genetic composition of the host is not only hereditary but undergoes rearrangements, integrations, and more subtle single-base pair alterations. These changes can be inconsequential or lead to aberrant and deleterious pathologic changes. In a complex multifactorial disease such as RA, the relative roles of the dynamic versus germline elements of the disease have yet to be fully determined. Further studies of large populations are likely to segregate out factors affecting specific ethnic, clinical, and genetic subgroups.
15180449 Common and uncommon features of rheumatoid arthritis and chronic obstructive pulmonary dis 2004 Jun Over the last decade it has become apparent that common pathogenic mechanisms are shared between many human chronic inflammatory diseases of unrelated pathology and manifestation. These mechanisms include common inflammatory networks that control tissue destructive and repair processes and their study is of major therapeutic potential as recently demonstrated for TNFalpha. Thus, early studies in rheumatoid arthritis defined TNFalpha as a major therapeutic target, the blockade of which was subsequently proved to be of great efficacy in the clinic. This paved the way for the successful blockade of TNFalpha in various other diseases including Crohn's disease, psoriasis, spondyloarthropathies and juvenile arthritis, although no similar networks with anti-TNFalpha at their apex had previously been demonstrated. In this article, we review the current knowledge of the pathogenic mechanisms involved in rheumatoid arthritis and chronic obstructive pulmonary disease with particular emphasis on the role of inflammatory cytokines, chemokines, and tissue degrading enzymes as revealed by studies in the laboratory and the clinic. Direct comparison of these mechanisms may provide clues for a future therapy for these painful and incurable diseases.
15479870 The International Classification of Functioning, Disability and Health (ICF) Core Sets for 2004 Nov Today, patients' functioning is a central issue in medicine. Concepts, classifications, and measurements of functioning and health, such as the International Classification of Functioning, Disability and Health (ICF) are of prime importance in clinical practice, teaching, and research. This report compares the contents of three of the most widely used health status measures in rheumatoid arthritis (RA), namely the Health Assessment Questionnaire disability index (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2), and the Short Form health survey (SF-36) based on the ICF. In addition, their content is compared to the Comprehensive ICF Core Set for RA. The comparisons illustrate that the different health status measures cover different components, and that they cover the different components with different level of precision. Using the ICF as a reference framework allows a researcher or a recommending instance to see which domains are covered in a specific instrument and, therefore, whether it is necessary to complement the study with other measures. Nevertheless, which specific health status measures to recommend still remains a challenge. If enough care is taken to define "what should be measured", it could form the basis for a solid and stable recommendation, adhered to for many years.
12822009 [Training effects on pain in rheumatoid arthritis]. 2003 May 29 BACKGROUND: This report considers the relationship between the effect of training on pain and joint manifestations in patients with rheumatoid arthritis. METHODS: A review of randomized controlled trials published from 1997 to February 2001. RESULTS: Six randomized controlled trials confirm results from previous research indicating that exercise leads to unchanged or reduced self-reported pain and unchanged or reduced tender joint counts in patients in ACR functional classes I or II with low to moderate disease activity. This effect may possibly be generalized to patients with higher disease activity. The effect is less clearly demonstrated in patients with serious joint destruction and loss of function. INTERPRETATION: The results indicate that exercise leads to unchanged or reduced self-reported pain and joint tenderness for patients with rheumatoid arthritis. Further studies are needed in order to demonstrate to what extent and how different kinds of exercise influence pain and joint tenderness in rheumatoid arthritis patients.
15316124 The NOAR Damaged Joint Count (NOAR-DJC): a clinical measure for assessing articular damage 2004 Dec OBJECTIVES: To evaluate the reliability and validity of the Norfolk Arthritis Register Damaged Joint Count (NOAR-DJC) in patients with early inflammatory polyarthritis (IP). METHODS: The NOAR-DJC examines deformity in 51 joints. Deformity is defined as inability to adopt the anatomical position, reduction in range of movement by at least one-third, and/or surgical alteration of the joint. Reliability was investigated by assessing intra- and inter-observer agreement in 40 and 32 patients, respectively. Validity was assessed by correlating the NOAR-DJC with the eroded joint count (criterion validity), the Health Assessment Questionnaire (HAQ) (convergent construct validity) and tender and swollen joint counts (divergent construct validity) and by discriminating between those who did and did not satisfy criteria for rheumatoid arthritis (discriminant validity). RESULTS: The intraclass correlation coefficient for the intra- and inter-rater studies were 0.88 [95% confidence interval (CI) 0.79, 0.94, P<0.00001] and 0.74 (95% CI 0.53, 0.86, P<0.00001), respectively. Correlations with eroded joint counts and HAQ scores after 5 yr follow-up were r(s) = 0.42 (95% CI 0.35, 0.49, P<0.01) and r(s) = 0.45 (95% CI 0.4, 0.5, P<0.01), respectively. Correlations with tender and swollen joint counts were weak (r(s) = 0.28 and r(s) = 0.33). CONCLUSION: The NOAR-DJC is a quick, reliable and valid tool for assessing articular damage in patients with early IP.
12468813 Evidence from clinical trials and long-term observational studies that disease-modifying a 2002 Dec Earlier reports, including a comprehensive 1983 review, had indicated that slowing of radiographic progression was relatively unusual in treatment of rheumatoid arthritis (RA) using traditional disease modifying anti-rheumatic drugs. However, in recent years, slowing of radiographic progression has been documented in a number of clinical trials, as well as long-term observational studies, with use of (in alphabetical order) adalimumab, anakinra, corticosteroids, cyclophosphamide, cyclosporin, etanercept, gold salts, infliximab, leflunomide, methotrexate and sulphasalazine. At this time, disease modification is a realistic goal in the clinical care of patients with RA. Documentation of improved long-term outcomes requires long-term observational data over 5-20 yr to supplement data from randomized controlled clinical trials over 6-24 months.
12121670 High dose chemotherapy and autologous hematopoietic stem cell transplantation for rheumato 2002 Aug A new treatment approach, involving intense immunosuppression and autologous hematopoietic stem cell transplantation (SCT), has emerged in recent years for the treatment of severe, refractory rheumatic autoimmune diseases including rheumatoid arthritis (RA). The rationale of this strategy is based on the concept of immunoablation by intense immunosuppression with subsequent regeneration of naïve T lymphocytes derived from reinfused hematopoietic progenitor cells. Patients with a therapy-refractory, progressively erosive disease who are at risk of functional disability and early mortality are considered eligible for treatment with autologous SCT. The goal is long-term improvement of disease activity and quality of life. However, when offering SCT to RA patients these benefits should be balanced against toxicities and treatment-related mortality. In several patients with intractable RA, long-term remissions were observed with this strategy, but failures have been reported as well. Only small numbers of RA patients have been treated thus far. Although different treatment protocols have been used, high dose chemotherapy as a means to achieve immunoablation has been invariably used in all studies. In this review we discuss background, clinical results, protocols, and future prospects of high dose chemotherapy and autologous SCT for RA.
12380395 [Significance of physical activity for bone mass and fracture risk in patients with rheuma 2002 Sep 23 Subjects with rheumatoid arthritis (RA) have reduced bone mineral density (BMD) and at least a twofold increased risk of osteoporotic fractures. Several factors, including the inflammatory process itself, treatment with glucocorticoids, and physical inactivity have been suggested as being implicated in the aetiology. Only a few studies, however, have examined the value of physical activity for the maintenance of BMD in RA. Cross-sectional studies have shown associations between BMD and indirect measures of physical activity, such as muscle strength and a self-reported degree of physical activity and functional capacity. Only three randomised controlled trials have been performed and none of these were able to demonstrate that exercise had an effect on BMD. Whether physical activity is associated with a reduced risk of fracture has only been addressed in a few cross-sectional studies, which yielded conflicting results, and has not yet been examined in longitudinal trials. Consequently, there is no evidence that physical exercise reduces bone loss and risk of fracture in RA. It is well-known, however, that immobilisation leads to rapid bone loss and should therefore be avoided.
16366138 Cardiovascular risk and rheumatoid arthritis: from mechanisms of atherosclerosis to therap 2004 Large epidemiological studies showed that one of the most important causes of death in patients with rheumatoid arthritis (RA) is represented by cardiovascular disease. Thus, the presence of RA is associated with an increased risk of the occurrence of stable angina, myocardial infarction, heart failure and stroke. However, studies performed during the last years failed to bring us clear evidence regarding the role of traditional cardiovascular risk factors (hyperlipidemia, diabetes mellitus, hypertension, smoking and obesity) in the pathogenesis of cardiovascular disease in these patients. Recently, the role of inflammation and its mediators not only in the atherosclerosis plaque development but also in the mechanisms of vulnerable plaque was clearly demonstrated. From this point of view, recent studies showed that inflammatory cells and mediators of inflammation are both markers of an increased cardiovascular risk and unfavorable cardiovascular outcome, and also cardiovascular risk factors that act in an active manner in the processes that promote atherosclerosis. Taking into account the fact that RA is a systemic inflammatory status, recent reports demonstrated the involvement of inflammation mediators in connection with prothrombotic factors and endothelial dysfunction in the development of cardiovascular disease in RA patients. There are only scarce data in the literature regarding the benefice of cardiovascular risk reduction therapies in this group. Further studies are required for the refinement of the cardiovascular risk stratification algorithms and for the improvement of the cardiovascular risk management in rheumatoid arthritis.
15130461 The clinical and cost-effectiveness of anakinra for the treatment of rheumatoid arthritis 2004 May OBJECTIVES: To review the evidence of the clinical and cost-effectiveness of anakinra, an interleukin-1 receptor antagonist (IL-1Ra), for the treatment of rheumatoid arthritis (RA) in adults. DATA SOURCES: Electronic bibliographic databases. Scrip, Food and Drug Administration (FDA) submissions for new drug applications, European Agency for the Evaluation of Medicinal Products (EMEA) reports and the pharmaceutical company submission to the National Institute for Clinical Excellence. REVIEW METHODS: Studies were identified that included randomised controlled trials (RCTs) or economic evaluations of anakinra in adult patients with RA. Existing health economic reviews were also assessed. Data were extracted and quality assessed using a structured approach. The Birmingham Rheumatoid Arthritis Model (BRAM) was used to compare disease-modifying antirheumatic drug (DMARD) sequences, chosen to reflect current clinical practice, with and without anakinra, at different points in the DMARD sequence. RESULTS: Five high-quality RCTs of anakinra in adult patients with RA, involving a total of 2905 patients, of whom 2146 received anakinra, were identified. The results of the clinical trials were consistent with clinical benefit (compared with placebo) as measured by American College of Rheumatology (ACR) composite response rate at 6 months. Variation in response rate was seen across the trials, which is likely to be a reflection of the size of the trials and the wide range of doses evaluated. Consistent benefit was seen at the higher dose evaluated. Benefit was evident both with monotherapy and when used in combination with methotrexate. Data on the efficacy end-points evaluated in a large pragmatic safety study have not been made available, which is of concern. Anakinra treatment was associated with a high incidence of injection-site reactions. Serious adverse events were infrequent, but longer term follow-up is required. No fully published economic evaluations of anakinra in patients with RA were identified. The BRAM gives a base-case estimate of the incremental cost-effectiveness ratio (ICER) of anakinra of 106,000 pounds to 604,000 pounds/quality-adjusted life-year (QALY). In the sensitivity analyses substantial variations were made in key parameters and ICERs were shown to be responsive. However, ICERs did not drop below 50,000 pounds/QALY in any univariate sensitivity analysis. CONCLUSIONS: Anakinra can be considered modestly effective in the treatment of RA based on ACR response, although no conclusion can currently be made on the effect of treatment on disease progression. Adjusted indirect comparison suggests that anakinra may be significantly less effective at relieving the clinical signs and symptoms of RA, as measured by the ACR response criteria, than tumour necrosis factor (TNF) inhibitors all used in combination with methotrexate, although these results should be interpreted with caution. The BRAM produces an ICER for anakinra substantially higher than those for infliximab and etanercept. However, patients may respond to anakinra when they have not responded to other TNF inhibitors, as these agents have a different mechanism of action. Thus, anakinra may produce a clinically significant and important improvement in some patients that they could not otherwise have achieved. Further research would be valuable in the following areas: RCTs to evaluate the efficacy, safety and cost of anakinra over the longer term; comparative trials of anakinra with other DMARDs and biological modifiers; assessment of the role of anakinra in the treatment of patients who have failed to achieve a benefit while taking infliximab or etanercept; assessment on the impact of DMARDs and anakinra on joint replacement, mortality and quality of life; controlled clinical trials of combination therapy with two anticytokines; investigations into newer biological therapies; and the utility of radiographic outcomes in clinical trials of RA.
15271772 Lower limb arterial incompressibility and obstruction in rheumatoid arthritis. 2005 Mar BACKGROUND: Despite increased cardiovascular morbidity and mortality in rheumatoid arthritis, the peripheral arteries remain understudied. OBJECTIVE: To examine the lower limb arteries in age and sex matched, non-smoking subjects with and without rheumatoid arthritis. METHODS: The ankle-brachial index (ABI) was measured at the posterior tibial and dorsal pedal arteries. Arteries were classified as obstructed with ABI < or =0.9, normal with ABI >0.9 but < or =1.3, and incompressible with ABI >1.3. Multinomial logistic regression was used to estimate differences in ABI between patients and controls, adjusting for cardiovascular risk factors, rheumatoid arthritis manifestations, inflammation markers, and glucocorticoid dose. RESULTS: 234 patients with rheumatoid arthritis and 102 controls were studied. Among the rheumatoid patients, 66 of 931 arteries (7%) were incompressible and 30 (3%) were obstructed. Among the controls, three of 408 arteries (0.7%) were incompressible (p = 0.002) and four (1%) were obstructed (p = 0.06). At the person level, one or more abnormal arteries occurred among 45 rheumatoid patients (19%), v five controls (5%, p = 0.001). The greater frequency of arterial incompressibility and obstruction in rheumatoid arthritis was independent of age, sex, and cardiovascular risk factors. Adjustment for inflammation markers, joint damage, rheumatoid factor, and glucocorticoid use reduced rheumatoid arthritis v control differences. Most arterial impairments occurred in rheumatoid patients with 20 or more deformed joints. This subgroup had more incompressible (15%, p< or =0.001) and obstructed arteries (6%, p = 0.005) than the controls, independent of covariates. CONCLUSIONS: Peripheral arterial incompressibility and obstruction are increased in rheumatoid arthritis. Their propensity for patients with advanced joint damage suggests shared pathogenic mechanisms.
15638416 From immunohistochemistry to pathophysiology of rheumatoid arthritis: cross reactivity of 2004 The mechanism of initiation and development of rheumatoid arthritis was a subject of several hypotheses. None of those hypotheses has, however, convincingly explained all important facts, related to clinical, immunological and pathological aspects of the disease. A hypothesis is presented here, suggesting that, in the course of rheumatoid arthritis, an immune system produces anti-immunoglobulin antibodies, cross-reacting with self collagen(s). This cross-reactivity may be a significant part of the complex set of pathological phenomena, characteristic for rheumatoid arthritis. The hypothesis originated from the author's own observations of binding of the anti-immunoglobulin antibodies to the fibrous connective tissue (presumably to collagens contained in it) in histological sections, subjected to immunohistochemical procedures.
12491120 [Current aspects of cost effectiveness of TNF-alpha blocking agents in patients with rheum 2002 Facing increasing health-related costs and limited health care resources, the assessment of cost effectiveness (CE) of medical procedures is also gaining considerable importance in the field of rheumatology. Since high annual therapy costs of 17,000-21,000 Euro are related to the employment of TNF-alpha blocking agents such as etanercept and infliximab (compared to annual costs of 350-5000 Euro of other disease modifying drugs (DMARDs) in the treatment of rheumatoid arthritis (RA)), their CE has become an important issue. The present investigation summarizes economic evaluations of cost and effectiveness of TNF-alpha blocking agents and compares the results to those of traditional DMARD therapies in patients with RA. The implications of these economic results on the further use of TNF-alpha blocking drugs and methodological improvements of their economic evaluation are discussed. The current literature provides evidence for the CE of the combination therapy with methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SASP). In comparison to this finding, the use of etanercept and MTX yields much higher costs, although the highest rate of ACR20 responses is achieved by this combination (additional costs of $42,000 per ACR20 response compared to combination of MTX, HCQ, and SASP). Two recent studies show more promising results of about $12,000/QUALY and even cost savings per QUALY administering etanercept and infliximab, respectively. The wide range of the CE ratios is mainly explained by different methodological approaches. Whether the wider employment of TNF-alpha blocking drugs (comprising not only selected patients) proves to be economically effective, remains to be investigated by further economic analyses. In contrast to the initial disappointing results of the comparison of established DMARD therapies and TNF-alpha blocking drugs in terms of CE, recently published data renders evidence that the CE of the TNF-alpha blocking drugs is comparable to other accepted therapies in internal medicine.
12645407 [Risk factors of rheumatoid arthritis]. 2003 Mar 3 Rheumatoid arthritis is a chronic inflammatory joint disease with an annual incidence rate between 25 and 50 per 100,000 individuals. Most likely, a combination of inherited and environmental factors, such as infections, reproductive or hormonal factors, and factors related to life style, is responsible for the disease. Future etiological studies should aim at providing a better insight into the interaction between different risk factors.
11954894 Hyperviscosity syndrome in rheumatoid arthritis with Felty's syndrome: case report and rev 2002 Feb Hyperviscosity syndrome (HVS) is characterised by high serum viscosity and the involvement of multiple organs, commonly causing retinal haemorrhage, bleeding diathesis, pulmonary hypertension, congestive heart failure (CHF), neurologic deficits and death. It has been reported that HVS is mostly encountered in Waldenström's macroglobulinaemia (80%-90% of all HVS cases) and occasionally in multiple myeloma. HVS in patients with connective tissue diseases (CTD) has rarely been reported. Of 28 cases of HVS reported in patients with CTD, 19 were with seropositive rheumatoid arthritis (RA). However, only six of these 19 cases had Felty's syndrome. Here we report another case of HVS in a patient with RA as well as Felty's syndrome.
12102273 Clinical practice among rheumatologists: managing patients with rheumatoid arthritis. 2002 May The objective of this study was to review evaluations of current clinical practice among rheumatologists managing patients with rheumatoid arthritis. We reviewed articles retrieved through PubMed using the search terms 'rheumatoid arthritis', 'clinical practice', 'physician's practice patterns', and 'health service research'. We set the time limits at January 1990 and May 2001. Marked variability was found in initial tests, initial treatment, changes in clinical status by number of visits, second-line treatment prescription and monitoring, use of monitoring criteria, clinical outcomes by type of health care insurance, and management of a fictional case. The data were obtained by survey in some studies and by prospective collection in others. This literature review indicates a need for developing recommendations for the management of rheumatoid arthritis.