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ID PMID Title PublicationDate abstract
15987496 Soluble RAGE: a hot new biomarker for the hot joint? 2005 The receptor for advanced glycation endproducts (RAGE) interacts with distinct ligand families linked to the inflammatory response. Studies in animal models suggest that RAGE is upregulated in the inflamed joint and that blockade of the receptor, using a ligand decoy soluble form of RAGE (sRAGE), attenuates joint inflammation and expression of inflammatory and tissue-destructive mediators. In this issue of Arthritis Research & Therapy, Rille Pullerits and colleagues reported that plasma levels of sRAGE were reduced in subjects with rheumatoid arthritis compared with healthy controls or subjects with non-inflammatory joint disease. These findings suggest the possibility that levels of sRAGE might be a biomarker of inflammation. Not resolved by these studies, however, is the intriguing possibility that endogenously higher levels of sRAGE might be linked to a lower incidence of arthritis or to the extent of inflammation. Nevertheless, although 'cause or effect' relationships may not be established in this report, fascinating insights into RAGE, inflammation and human arthritis emerge from these studies.
15784470 Eotaxin-3 gene polymorphisms are associated with rheumatoid arthritis in a Korean populati 2005 Mar The eotaxin gene family (eotaxin, eotaxin-2, and eotaxin-3) has been implicated in the recruitment of eosinophils, basophiles and Th2 lymphocytes that is a central aspect of allergic diseases. We previously suggested that Eo2+179T>C and Eo2+275C>T of the eotaxin-2, and Eo3+2497T>G of the eotaxin-3 were significantly associated with susceptibility to asthma. To precisely determine whether these single nucleotide polymorphisms (SNPs) are associated with susceptibility to autoimmune disease such as rheumatoid arthritis (RA) in Koreans, we analyzed the genotype and allele frequencies for four SNPs (Eo2+179T>C, Eo2+275C>T, Eo2+304A>C, and Eo2+1272A>G) of the eotaxin-2, and three SNPs (Eo3+77C>T, Eo3+1577G>A, and Eo3+2497T>G) of the eotaxin-3 by single-base extension method. Although the genotype and allele frequencies of the eotaxin-2 SNPs gene between patients with RA and controls were not significantly different, the genotype and allele frequencies of the eotaxin-3SNPs between them were significantly associated. The genotype frequencies of Eo3+1577G>A and Eo3+2497T>G in patients with RA were significantly different from those in the controls (p = 0.0001 and p < 0.0001, respectively). Our results strongly suggest that the polymorphisms of eotaxin-3 might be associated with susceptibility to RA.
17709949 Stress as a risk factor in the pathogenesis of rheumatoid arthritis. 2006 Stress is now recognized as an important risk factor in the pathogenesis of autoimmune rheumatic diseases (i.e. rheumatoid arthritis) by considering that the activation of the stress response system influences the close relationships existing between the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system and the immune system. The stress response results in the release of neurotransmitters (norepinephrine), hormones (cortisol) and immune cells which serve to send an efferent message from the brain to the periphery. Major life events lead to an intense release of stress mediators (large time integral of released neurotransmitters and hormones), whereas in minor life events, only short-lived surges of neurotransmitters and hormones are expected. Therefore, it is suggested that neurotransmitters such as norepinephrine or stress hormones such as cortisol might have different effects on immune/inflammatory responses at high and low concentrations present during short or extended periods of time, respectively. Long-lasting (chronic) stress may lead to proinflammatory effects because no adequate long-term responses of stress axes (anti-inflammatory) are to be expected.
17195414 Impact of treatment with infliximab on anticyclic citrullinated peptide antibody and rheum 2006 Nov OBJECTIVE: To investigate the impact of infliximab treatment on anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) levels in patients with rheumatoid arthritis (RA). METHODS: Sera from 33 RA patients receiving infliximab and disease modifying antirheumatic drugs were tested for anti-CCP antibody, IgA-, IgG- and IgM-RF using a commercially available semiquantitative ELISA at baseline, 30 and 54 weeks after treatment. RESULTS: The serum levels of anti-CCP antibody and IgA-RF decreased significantly after 30 weeks (P = 0.002 and 0.024); however, the decrease was not significant at week 54 (P = 0.147 and 0.207). The decrease in IgG-RF level was not significant at 30 and 54 weeks (P = 0.059 and 0.097). IgM-RF levels, however decreased significantly at 30 and 54 weeks (P = 0.002 and 0.004). A strong correlation between anti-CCP and IgA-, IgG- and IgM-RF was observed at baseline (r(s) = 0.48, 0.43, 0.65, P = < 0.05) and after infliximab treatment at 30 (r(s) = 0.45, 0.46, 0.62, P = < 0.05) and 54 (r(s) = 0.49, 0.45, 0.60, P = < 0.05) weeks. CONCLUSION: Treatment with infliximab results in decreased anti-CCP antibody and IgA-RF early in the course of therapy that is not sustained. IgM-RF declines and remains decreased for at least 54 weeks. Investigations in larger cohorts of RA patients (especially early RA) with longer follow-up are needed to assess the impact of specific therapeutic interventions on anti-CCP antibody and RF levels and the relationship of their levels to disease activity.
15973463 Peripheral blood gene expression profiling in rheumatoid arthritis. 2005 Aug We carried out gene expression profiling of peripheral blood mononuclear cells (PBMCs) in 29 patients with active rheumatoid arthritis (RA) and 21 control subjects using Affymetrix U95Av2 arrays. Using cluster analysis, we observed a significant alteration in the expression pattern of 81 genes (P<0.001) in the PBMCs of RA patients compared with controls. Many of these genes correlated with differences in monocyte counts between the two study populations, and we show that a large fraction of these genes are specifically expressed at high levels in monocytes. In addition, a logistic regression analysis was performed to identify genes that performed best in the categorization of RA and control samples. Glutaminyl cyclase, IL1RA, S100A12 (also known as calgranulin or EN-RAGE) and Grb2-associated binding protein (GAB2) were among the top discriminators. Along with previous data, the overexpression of S100A12 in RA patients emphasizes the likely importance of RAGE pathways in disease pathogenesis. The altered expression of GAB2, an intracellular adaptor molecule involved in regulating phosphatase function, is of particular interest given the recent identification of the intracellular phosphatase PTPN22 as a risk gene for RA. These data suggest that a detailed study of gene expression patterns in peripheral blood can provide insight into disease pathogenesis. However, it is also clear that substantially larger sample sizes will be required in order to evaluate fully gene expression profiling as a means of identifying disease subsets, or defining biomarkers of outcome and response to therapy in RA.
14530867 An open, randomized comparison study of cyclosporine A, cyclosporine A + methotrexate and 2005 Jan PURPOSE: To determine whether a regimen of cyclosporine (CSA) and methotrexate (MTX), or CSA and hydroxychloroquine (HCQ) introduced in early rheumatoid arthritis (RA) can produce a significant improvement in clinical outcome and/or retard radiographic damage in comparison with standard monotherapy with CSA alone. METHODS: One hundred five patients with active RA of less than 36 months duration, who had never previously been treated with immunosuppressive agents, were included in a 12-month, multi-center, open, randomized trial. Patients who fulfilled the criteria for early severe RA were randomized to receive either combination therapy (CSA + MTX n = 34, CSA + HCQ n = 35) or CSA alone (n = 36). RESULTS: CSA + MTX was more effective than the other two treatment groups in controlling RA symptoms. CSA+MTX did not show a significant radiographic progression according to Larsen-Dale (0.90 +/- 3.89 compared to baseline values, P > 0.05); moreover, patients treated with CSA alone or CSA+HCQ showed a significant worsening of Larsen-Dale score (2.91 +/- 5.99 and 2.97 +/- 4.28 respectively vs baseline values, P < 0.05), although not significant when compared with the CSA + HCQ group (P = 0.56 and 0.39, respectively). CONCLUSIONS: This trial indicated that CSA+MTX was more effective than the other two treatments in improving clinical data and inhibiting radiographic progression, although the differences were not significant in this relatively small study. However, the difference was significant in favor of CSA + MTX regarding ACR 50% response.
16273784 The consequences of rheumatoid arthritis: quality of life measures in the individual patie 2005 Sep Despite conventional treatment, RA still has many deleterious consequences. From the patients' perspective, these include persistent pain, functional disability, fatigue, and depression modified by health beliefs and underlying psychological problems. Disability is a consequence of pain, active synovitis and joint damage. It is usually assessed by self-reported questionnaire; the Health Assessment Questionnaire (HAQ) remains the dominant disability measure, although generic health measures such as Short Form-36 and Nottingham Health Profile provide similar information. Treatment with disease modifying drugs and biologic agents improves pain, fatigue and disability. We specifically evaluated the effects of both these drugs and also disease duration on disability assessed by HAQ scores, as there is most information on this topic and it is of fundamental importance to patients. In early RA HAQ gives a 'J-shaped' curve; the initial fall is due to the immediate benefits of treatment and the subsequent gradual rise due to the inability of therapy to fully suppress the disease or prevent progressive joint damage. In established RA HAQ scores increase by about 1% annually and over 25 years average HAQ scores increase by 1.0. Disease modifying drugs and biologics both significantly reduce HAQ scores and the reduction is maintained for 2-5 years. This reduction is seen in both early and established disease. Early steroid therapy has immediate symptomatic treatment, but does not have long-term benefits. Over 5 years the impact of aggressive therapy with disease modifying drugs declines and there is evidence that insufficient treatment is given to many patients with RA. The outcome of RA is greatly improved by current treatment with disease modifying drugs and biologic agents. However, more needs to be done and achieving better results is enhanced by routinely measuring the impact of the disease in routine practice.
17170055 Ultrasonographic measurement of the median nerve in patients with rheumatoid arthritis wit 2007 Jun OBJECTIVES: Ultrasonography (US) has shown increased cross-sectional area of the median nerve in carpal tunnel syndrome (CTS). Knowledge of the normal distribution of the areas is a prerequisite to evaluate pathology. Presently, the distribution of cross-sectional areas of the median nerve was explored in patients with rheumatoid arthritis (RA). METHODS: The median nerves of patients with RA having no symptoms or signs of CTS were examined with bilateral US at the entrance of the carpal tunnel. RESULTS: A total of 154 patients with RA were included. The median nerve was divided in 11.7% of the hands. The mean (SD) cross-sectional areas of the undivided median nerves were not significantly different on either sides (8.3 (1.5) mm(2) on the right side and 8.3 (1.4) mm(2) on the left side). The areas of the examined 308 median nerves ranged from 5.0 to 12.8 mm(2), with the 97.5 centile being 11.1 mm(2). Areas >10.0 mm(2) were found in 10% of the patients. CONCLUSIONS: The mean cross-sectional areas of the median nerve in patients with RA were similar to those reported in healthy controls. However, 10% of the patients had values that overlap with areas commonly reported in patients with mild idiopathic CTS.
16941197 Anxiety and depression in patients with rheumatoid arthritis. 2007 Jun Rheumatoid arthritis (RA) mostly follows a painful, progressively disabling course, and individuals with RA experience more psychological distress than healthy individuals. The objective of the present study is to examine the prevalences of accompanying anxiety and depression in RA cases. The study included 82 RA cases and 41 age- and sex-matched healthy volunteers as the control group. Psychiatric examinations of all cases of the patient and control groups were performed according to DSM-IV criteria. Hamilton Anxiety Scale or Hamilton Depression Scale was applied to those who were found to have anxiety or depression. Total prevalence of anxiety, depression, and mixed anxiety-depressive disorder was found to be 70.8% (n=58) in the patient group and 7.3% (n=3) in the control group, and the difference was significant (p<0.001). Of the RA patients, 41.5% (n=34) was found to have depression, 13.4% (n=11) anxiety, and 15.9% (n=13) mixed anxiety-depressive disorder. The disease duration in patients with anxiety was shorter than the RA patient with depression (p<0.05). The disease duration was positively correlated with the degree of depression and negatively correlated with the degree of anxiety (r=0.341, p<0.05; r=-0.642, p<0.05, respectively). The results of our study suggest that prevalences of anxiety and mainly depression, increase in RA cases. When the clinical picture in RA cases becomes complicated with anxiety or depression, some problems at patients' adaptation and response to treatment may be possible. RA cases should be monitored for accompanying anxiety or depression during follow-up.
17279204 Care pathways in early rheumatoid arthritis. 2006 Nov OBJECTIVE: To determine the proportion of family physicians who diagnose rheumatoid arthritis (RA) correctly and to note how they report they would manage RA patients. DESIGN: Mailed survey (self-administered questionnaire) requesting comments on vignettes. SETTING: Province of Quebec. PARTICIPANTS: Computer-generated random sample of family physicians registered with the Quebec College of Family Physicians. MAIN OUTCOME MEASURES: The proportion of family physicians who recognized RA and their reported management strategies. RESULTS: Most respondents recognized the vignette presentation as a case of RA; 133/138 (96.4%) indicated RA as their provisional diagnosis, and all but 1 of the remaining respondents listed RA as a differential diagnosis. Of those who considered RA as a provisional or possible diagnosis, 107 (77.5% of all respondents) suggested referring the patient to a rheumatologist. Among the physicians who suggested referral, none indicated they would initiate disease-modifying antirheumatic drugs (DMARDs). CONCLUSION: Almost all respondents considered RA as a provisional or differential diagnosis. Although many suggested referring the patient to a rheumatologist, almost a quarter did not. Initiating DMARDs before referring patients to rheumatologists appears to be rare. Since DMARDs given during the early stages of RA are known to decrease damage and dysfunction, ways to increase their use and optimize care pathways for new-onset inflammatory arthritis are urgently needed.
16920570 Treatment of rheumatoid arthritis with rituximab: an update and possible indications. 2006 Aug Based on new biologic and clinical insights, the number of drugs blocking different biologic targets in rheumatoid arthritis (RA) [e.g., tumor necrosis factor alpha (TNFalpha), CTLA4, interleukin (IL)-1, IL-6, IL-15, IL-18, B lymphocyte stimulator (BLyS), CD20] has increased considerably over the last decade. Rituximab, a chimeric monoclonal antibody that was developed for the treatment of B-cell lymphomas, has been used in different autoimmune diseases where B-cells are thought to play a pivotal role. However, blinded randomised controlled trials have been completed only for RA so far, indicating the clear efficacy of B-cell blockade in RA and highlighting the pathogenetic B-cell in rheumatoid synovitis. The use of rituximab in RA is herein updated, from early preliminary studies to more recent presentations in International Conferences. Key clinical and biologic issues are discussed, i.e., efficacy and safety of rituximab, role of concomitant therapies, use in the long term and retreatment strategies, differences with anti-TNFalpha therapy. The possible indications in RA are finally discussed, also on the ground of personal experience with rituximab in RA and other rheumatic diseases associated with B-cell lymphoproliferation. Further clinical research should go hand in hand with laboratory research, and tissue studies are now needed.
15838230 Rheumatoid arthritis and cardiovascular disease: the role of systemic inflammation and evo 2005 May PURPOSE OF REVIEW: The incidence and mortality of cardiovascular disease are increased in the context of rheumatoid arthritis. The purpose of this review is to examine our evolving understanding of the pathogenesis of cardiovascular disease in rheumatoid arthritis and to underscore the importance of tailored prevention of cardiovascular disease in this select population. RECENT FINDINGS: Recent reports have highlighted the shared pathobiology of cardiovascular disease and rheumatoid arthritis, both of which represent inflammatory disorders. Several reports have also provided much-needed insight into the deleterious impact that select therapies (including cyclo-oxygenase-2-specific inhibitors) may have in terms of the risk of cardiovascular disease in rheumatoid arthritis. Although further study is warranted, preliminary investigations also suggest that aggressive anti-inflammatory therapy, including the adjunctive use of statins, may play important cardioprotective roles in rheumatoid arthritis. SUMMARY: The pathogenesis of cardiovascular disease in rheumatoid arthritis is complex and involves several intermediate factors, including dyslipidemia, elevations in serum homocysteine, impaired insulin sensitivity, and endothelial dysfunction. Given the burden of cardiovascular disease in this population, it is important that health care providers caring for rheumatoid arthritis patients adopt a treatment course that is both comprehensive and individualized to address specific risk factors for cardiovascular disease.
16426939 Fever of unknown origin caused by late-onset rheumatoid arthritis. 2006 Jan Fever of unknown origin (FUO) is always a diagnostic challenge. The causes of FUO are legion and may be due to malignancy, infection, collagen vascular disease, and a variety of other unusual disorders. Currently, malignancies-followed by infectious etiologies-are the most common cause of FUO. We present an elderly female patient with an FUO who was thought to have subacute bacterial endocarditis because of an antecedent history of recent dental work. Subacute bacterial endocarditis was ruled out on the basis of negative cultures and negative transesophageal echocardiography. No evidence for an infectious disease or neoplastic etiology could be demonstrated in this patient. The diagnosis of FUO is most difficult when there is a paucity of clues from the history and physical examination, as was the case in this patient. Nonspecific laboratory tests included highly increased erythrocyte sedimentation rate (>or=100 mm/h), highly increased C-reactive protein, relative lymphocytopenia, and chronic thrombocytosis. These findings are compatible with a variety of infectious and inflammatory disorders. No evidence could be found for vasculitis. The only laboratory diagnostic findings present in her case were a highly increased rheumatoid factor titer and perinuclear antineutrophilic cytoplasmic antibody level. Polymyalgia rheumatica/temporal arteritis, systemic lupus erythematosus, and adult Still's disease were ruled out. The patient's FUO was best explained by the finding of late-onset rheumatoid arthritis (LORA), which is characterized by acute onset in elderly patients without the usual musculoskeletal manifestations of rheumatoid arthritis. Both the highly increased rheumatoid factor titer and perinuclear antineutrophilic cytoplasmic antibody level in the absence of an alternate explanation indicate that the FUO in this patient was caused by LORA.
16079171 Growth and infectious exposure during infancy and the risk of rheumatoid factor in adult l 2006 Mar BACKGROUND: The contribution of the environment to rheumatoid arthritis (RA) remains uncertain. Intrauterine and early postnatal life may be important. Rheumatoid factor (RF) found in around 10% of the normal population confers a risk of developing RA and may be present years before onset of clinical disease. The immune pathology leading to RA and RF may have similar genetic and environmental influences. OBJECTIVE: To measure RF in people for whom data on birth weight, infant growth, and markers of infectious exposure during infancy and childhood, had been previously recorded. METHODS: 675 men and 668 women aged 59-67 years, born and still resident in Hertfordshire, UK, were studied. RF was measured with an ELISA. Associations between presence of RF, early growth, and markers of hygiene in infancy, were investigated. RESULTS: RF was detected in 112/675 (16.6%) men and 79/668 (11.8%) women. No significant relationships existed between early growth and presence of RF in men or women. Among women, sharing a bedroom during childhood was associated with a lower risk of RF positivity (OR = 0.48, 95% CI 0.30 to 0.78, p = 0.003). CONCLUSIONS: A developing immune system exposed to increased infectious exposure is less likely to produce RF in adult life; this may reduce the pathological process which leads to RA.
15804701 Autoantibodies to citrullinated proteins: ACPA. 2005 Feb Anti-perinuclear factor and anti-keratin antibodies have long been known to be specifically associated with rheumatoid arthritis (RA). They were first demonstrated to target various forms of (pro)filaggrin, a protein of stratified epithelia. Then, they were found to belong to a single family of autoantibodies targeting proteins that bear peptidic epitopes centered by a citrullyl residue: the anti-citrullinated protein autoantibodies (ACPA). The main targets of ACPA in the synovial tissue were demonstrated to be citrullinated forms of the a- and beta-chains of fibrin. A chronic conflict between locally produced ACPA and deposits of citrullinated fibrin is probably responsible for self-maintaining of RA synovial inflammation. Various tests for the detection of ACPA have been developed: recent ELISAs confirm their high diagnostic specificity and improve their diagnostic sensitivity. Since ACPA appear very early in the course of the disease, their detection is of major interest to identify RA among recent arthritides. Moreover, their prognostic value may lead to start early 'aggressive' treatments to prevent irreversible joint damage.
16840501 Polyarticular psoriatic arthritis is more like oligoarticular psoriatic arthritis, than rh 2007 Jan BACKGROUND: and objective: Since the original description of psoriatic arthritis (PsA) subgroups by Moll and Wright, there has been some discrepancy in the precise prevalence of the different subgroups and in particular the proportion of patients with polyarthritis. The higher prevalence of the polyarthritis subgroup may be due to the inclusion of patients with seronegative rheumatoid arthritis with coincidental psoriasis. The classification of psoriatic arthritis (CASPAR) study database provided an opportunity to examine this question. METHODS: The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician-diagnosed PsA and 525 controls with other inflammatory arthritis, 70% of whom had rheumatoid arthritis. Patients with PsA were divided into two groups: polyarthritis and non-polyarthritis (which included the Moll and Wright subgroups of spinal disease, distal interphalangeal predominant and arthritis mutilans) and were compared with patients with rheumatoid arthritis. Comparisons were made between all three groups and, if a significant difference occurred, between the two groups with PsA. RESULTS: The three groups differed significantly with regard to all clinical and laboratory variables except duration of disease. Significant differences were also found between the two groups of PsA in terms of age, sex, total number of involved joints, disability score and symmetry. However, no differences were found between the groups of patients with PsA in terms of seropositivity for rheumatoid factor and antibodies to cyclic citrullinated peptide, enthesitis, and spinal pain and stiffness. Further, dactylitis was commonly seen in patients with PsA (57% in the polyarticular group and 45% in non-polyarticular group), and uncommonly found in patients with rheumatoid arthritis (5%). With the exception of entheseal changes, syndesmophytes and osteolysis, typical radiological features of PsA could not be used to distinguish between the PsA subgroups. CONCLUSIONS: The evidence suggests that the changing prevalence of the polyarticular subgroup of PsA is not because doctors include patients with seronegative rheumatoid arthritis with coincidental psoriasis.
16229336 Evaluation of efficacy and tolerability of dothiepin hydrochloride in the management of ma 2005 May Several studies have shown that 20 to 66.2% of patients with rheumatoid arthritis have associated psychiatric comorbidity especially depression. Dothiepin hydrochloride is a well-established and effective antidepressant in patients with depressive symptoms of varying severity and co-existing anxiety. To document the efficacy and tolerability of dothiepin hydrochloride in the management of major depressive disorder (MDD) in rheumatoid arthritis patients a phase IV, open, single arm, prospective study was initiated with dothiepin hydrochloride in the dose of 75 mg/day, duration of therapy was 6 weeks. Twenty-five rheumatoid arthritis patients suffering from co-morbid MDD completed the 6-week dothiepin hydrochoride treatment and were considered for final analysis. There was significant reduction (p < 0.05) in mean HAM-D scores at week 2 (13.92 +/- 5.45), week 4 (9.28 +/- 4.13) and week 6 (5.72 +/- 3.26) compared to baseline (21.64 +/- 5.93). There was significant reduction (p < 0.05) in mean HAM-A scores at week 2 (6.52 +/- 3.34), week 4 (4.0 +/- 2.25) and week 6 (2.76 +/- 1.59) compared to baseline (10.68 +/- 3.68). The global impression of efficacy at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as marked and moderate improvement in 20 (80%) and 5 patients (20%) respectively. Only 2 patients reported dry mouth as an adverse event in the study. The overall assessment of tolerability at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as good and fair in 19 (76%) and 6 patients (24%) respectively. Dothiepin hydrochloride was found to be an effective and well-tolerated drug in the management of MDD and anxiety in patients suffering from rheumatoid arthritis.
15801012 Physical function and health related quality of life: analysis of 2-year data from randomi 2005 Apr OBJECTIVE: To determine whether improvements in physical function and health related quality of life (HRQOL) are sustained over 2 years of blinded treatment with leflunomide (LEF), methotrexate (MTX), or sulfasalazine (SSZ) in patients with active rheumatoid arthritis (RA). METHODS: Three phase III randomized, controlled trials compared LEF, MTX, and SSZ in patients with active RA. Improvements in physical function were assessed by Health Assessment Questionnaire Disability Index (HAQ-DI) and Modified Health Assessment Questionnaire (MHAQ); monthly MHAQ and mean HAQ scores were used to calculate American College of Rheumatology responses; HAQ-DI was assessed at baseline and 6-month intervals. In US301, the Medical Outcomes Study 36-Item Short-Form questionnaire (SF-36) assessed treatment-associated changes in HRQOL at baseline and 6-month intervals. RESULTS: Mean and median improvements in HAQ-DI after 12 and 24 months of active treatment in all phase III protocols significantly exceeded -0.22 or a minimum clinically important difference (MCID). These improvements closely reflected positive changes in SF-36 that met or exceeded MCID in all domains with LEF and MTX treatment. Problem Elicitation Technique Top 5 scores reflected improvements in performance of physical activities most important to patients. CONCLUSION: Improvements in physical function were sustained over 24 months of successful treatment with LEF, MTX, and SSZ, and reflected improvements in mental as well as physical domains of HRQOL.
15987497 Modeling human arthritic diseases in nonhuman primates. 2005 Models of rheumatoid arthritis (RA) in laboratory animals are important tools for research into pathogenic mechanisms and the development of effective, safe therapies. Rodent models (rats and mice) have provided important information about the pathogenic mechanisms. However, the evolutionary distance between rodents and humans hampers the translation of scientific principles into effective therapies. The impact of the genetic distance between the species is especially seen with treatments based on biological molecules, which are usually species-specific. The outbred nature and the closer anatomical, genetic, microbiological, physiological, and immunological similarity of nonhuman primates to humans may help to bridge the wide gap between inbred rodent strain models and the heterogeneous RA patient population. Here we review clinical, immunological and pathological aspects of the rhesus monkey model of collagen-induced arthritis, which has emerged as a reproducible model of human RA in nonhuman primates.
15940763 Can progressive resistance training reverse cachexia in patients with rheumatoid arthritis 2005 Jun OBJECTIVE: . A Phase II trial was performed as a preliminary test of the efficacy and safety of progressive resistance training (PRT) as adjunct treatment for rheumatoid cachexia. METHODS: Ten mildly disabled patients with well-controlled rheumatoid arthritis (RA) trained, on average, 2.5 times per week for 12 weeks. Ten age and sex matched RA patients with similar disease characteristics were non-randomly assigned to a control group. Body composition, physical function, and disease activity were assessed pre and post intervention period. RESULTS: Between group comparisons at followup by ANCOVA using baseline scores as covariate showed significant increases in fat-free mass (+1253 g, p = 0.004), total body protein (+1063 g, p = 0.044), and arm (+280 g, p = 0.005) and leg (+839 g, p = 0.001) lean mass (a proxy measure of total body skeletal muscle mass) in response to PRT with no exacerbation of disease activity. There was also a trend for loss of fat mass in the trunk (-752 g, p = 0.084) and a significant reduction in percent body fat (-1.1%, p = 0.047). Changes in body composition were associated with improvements in various measures of physical function. CONCLUSION: Intense PRT with adequate volume seems to be an effective and safe intervention for stimulating muscle growth in patients with RA. Pending confirmation of these results in a larger randomized controlled trial that includes patients with more active and severe disease, a similar PRT program should be included in the management of RA as adjunct treatment for cachexia.