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ID PMID Title PublicationDate abstract
24283221 MicroRNA-323-3p with clinical potential in rheumatoid arthritis, Alzheimer's disease and e 2014 Feb INTRODUCTION: MicroRNAs (miRNAs) are a group of noncoding RNAs,∼ 20 - 22 nucleotides in length, that repress target gene expression through mRNA degradation and translation inhibition. The gene encoding miR-323-3p, which is a biomarker in immune and inflammatory responses, exists in a miRNA cluster in chromosomal region 14q32.31. It has been shown that miR-323-3p associates with the pathogenesis of several diseases, such as rheumatoid arthritis, Alzheimer's disease and ectopic pregnancy. AREAS COVERED: This review provides a current view on the association of miR-323-3p with several human diseases and is focused on the recent studies of miR-323-3p regulation, discussing its potential as an epigenetic biomarker and therapeutic target for these diseases. In particular, the mechanisms of miR-323-3p in these diseases and how miR-323-3p is regulated are also discussed. EXPERT OPINION: Although the exact role of miR-323-3p in these diseases has not been fully elucidated, targeting miR-323-3p may serve as a promising therapy strategy.
24989966 Influence of angulation on metacarpal bone mineral density measurements using digital X-ra 2015 May OBJECTIVE: Digital X-ray radiogrammetry (DXR) is a computer-assisted technique used to quantify cortical bone density of the metacarpals. The influence of metacarpal bone rotation and type of cast material on bone mineral density (BMD) measurements using the DXR technique was tested. METHODS: The bone mineral density of the hand was measured by DXR, and rotation error (DXR-RE) as coefficients of variation were calculated, to verify reliability and reproducibility of this radiogeometric technique to assess in particular minor disease-related changes in the metacarpal bone mass. The reproducibility of the DXR measurements was also investigated using different cast materials (mull, elastic, and plastic). RESULTS: There were no significant changes in absolute values of DXR-BMD observed between 0 to [Formula: see text] angulation. The relative DXR-RE ranged between 0 % (degree 1) and 0.70 % (degrees 15 and 19) for DXR-BMD. Regarding the different cast materials, DXR-BMD revealed a coefficient of variation with 0.41 % (mull cast) and 0.21 % (elastic cast). For the plastic cast, the DXR technique was not able to perform an analysis of DXR-BMD. CONCLUSION: The study revealed no significant influence of metacarpal rotation on the measurements of metacarpal bone mineral density as estimated by DXR. DXR measurements are not optimal when cast material is used. DXR can accurately quantify periarticular cortical bone mass. This is significant especially for rheumatoid arthritis and related conditions where X-ray imaging of arthritic hands with varying degrees of deformity is performed.
23932312 Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, ca 2014 Feb OBJECTIVE: We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker. METHODS: The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early response was evaluated at week 16 as ±20% improvement in swollen/tender joint counts; and ACR50 was evaluated at week 52. Biomarkers (tissue inflammation: C3M, CRPM, and VICM; cartilage degradation: C2M; and bone turnover: CTx and osteocalcin) were tested in serum from baseline, week 4, 16, 24, and 52, and dose-dependent effect was investigated. Patients were divided into the following three groups: early non-responders (ENR), ACR50 responders, and non-responders; their biomarker profiles were compared. RESULTS: At week 52, CRP was inhibited to 4% and 40% of baseline by TCZ8 and TCZ4, respectively. CRPM (63%), C2M (84%), C3M (69%), and VICM (42%) were significantly (p < 0.05) reduced by TCZ8, but not by TCZ4. MMP3 and osteocalcin changed to <58% and >111%, respectively, in response to TCZ. CTx was not changed significantly. ENRs had significantly less inhibition of CRPM (p < 0.05), C2M (p < 0.01), and C3M (p < 0.01) compared to early responders. There was a significant difference in the C2M, C3M, and CRPM profiles of the ENRs, non-responders, and responders. ACR50 responders had significantly inhibited levels (p < 0.001), irrespective of dose. CONCLUSIONS: TCZ8 strongly inhibited the biomarkers of joint tissue remodeling suggesting that TCZ actively suppresses key pathobiological processes at the site of inflammation in RA patients. The differences in biomarkers' profiles of responders and non-responders indicate that specific responder profiles exist.
22941768 Association between a history of periodontitis and the risk of rheumatoid arthritis: a nat 2013 Jul OBJECTIVE: To investigate the association between the risk of rheumatoid arthritis (RA) and a history of periodontitis. METHODS: This nationwide, population-based, case-control study used administrative data to identify 13 779 newly diagnosed patients with RA (age ≥16 years) as the study group and 137 790 non-patients with RA matched for age, sex, and initial diagnosis date (index date) as controls. Using conditional logistic regression analysis after adjustment for potential confounders, including geographical region and a history of diabetes and Sjögren's syndrome, ORs with 95% CI were calculated to quantify the association between RA and periodontitis. To evaluate the effects of periodontitis severity and the lag time since the last periodontitis visit on RA development, ORs were calculated for subgroups of patients with periodontitis according to the number of visits, cumulative cost, periodontal surgery and time interval between the last periodontitis-related visit and the index date. RESULTS: An association was found between a history of periodontitis and newly diagnosed RA (OR=1.16; 95% CI 1.13 to 1.21). The strength of this association remained statistically significant after adjustment for potential confounders (OR=1.16; 95% CI 1.12 to 1.20), and after variation of periodontitis definitions. The association was dose- and time-dependent and was strongest when the interval between the last periodontitis-related visit and the index date was <3 months (OR=1.64; 95% CI 1.49 to 1.79). CONCLUSIONS: This study demonstrates an association between periodontitis and incident RA. This association is weak and limited to lack of individual smoking status.
23651570 The two directions of TNF-related apoptosis-inducing ligand in rheumatoid arthritis. 2013 Aug The TNF-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) superfamily that has been recognized for its specific pro-apoptotic effect on cancer cells and has been therefore proposed as a treatment in cancer. Studies on animal models have shown that TRAIL could also have a beneficial effect in rheumatoid arthritis (RA). This includes reports suggesting that TRAIL could be used to control the synovial hyperplasia and hyperactivation of immune cells observed in RA, but recent reports suggest a disease promoting role of TRAIL in RA. Indeed, adverse effects and mechanism of resistance could counteract beneficial effect of TRAIL. This review focuses on the role of TRAIL in immune regulation, synovial hyperplasia and joint remodeling in RA. We will also discuss the potential use of TRAIL in RA treatment.
23334450 Epigenome-wide association data implicate DNA methylation as an intermediary of genetic ri 2013 Feb Epigenetic mechanisms integrate genetic and environmental causes of disease, but comprehensive genome-wide analyses of epigenetic modifications have not yet demonstrated robust association with common diseases. Using Illumina HumanMethylation450 arrays on 354 anti-citrullinated protein antibody-associated rheumatoid arthritis cases and 337 controls, we identified two clusters within the major histocompatibility complex (MHC) region whose differential methylation potentially mediates genetic risk for rheumatoid arthritis. To reduce confounding factors that have hampered previous epigenome-wide studies, we corrected for cellular heterogeneity by estimating and adjusting for cell-type proportions in our blood-derived DNA samples and used mediation analysis to filter out associations likely to be a consequence of disease. Four CpGs also showed an association between genotype and variance of methylation. The associations for both clusters replicated at least one CpG (P < 0.01), with the rest showing suggestive association, in monocyte cell fractions in an independent cohort of 12 cases and 12 controls. Thus, DNA methylation is a potential mediator of genetic risk.
25261597 Increased levels of serum myeloperoxidase in patients with active rheumatoid arthritis. 2014 Nov 4 AIMS: The clinical significance of myeloperoxidase (MPO) has been the focus of investigation because it may contribute to the chronic, non-microbial inflammatory process in various diseases. Here, we determined serum MPO levels in rheumatoid arthritis (RA) and other autoimmune or inflammatory conditions, and investigated the associations between MPO levels and disease activity indicators in RA. MAIN METHODS: The distribution of MPO was determined in serum samples from patients with RA, systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), dermatomyositis (DM), or ankylosing spondylitis (AS) and from healthy controls using commercial ELISA kits. Associations of serum MPO levels with the disease variables of RA patients were evaluated. KEY FINDINGS: All patient samples analyzed showed higher serum levels of MPO than healthy controls. Furthermore, MPO levels in RA were significantly higher than those in the other diseases with the exception of DM. Higher MPO levels were observed in RA patients with increased C-reactive protein (p=0.005) or neutrophil percentage (p<0.001), as well as in those with highly active disease (p<0.001). Moderate positive correlations between MPO levels and IgM (r=0.334, p=0.001), C-reactive protein (r=0.293, p=0.003), erythrocyte sedimentation rate (r=0.240, p=0.016), or DAS28 (r=0.350, p<0.001) were also demonstrated. SIGNIFICANCE: The MPO concentration is likely to increase in patients with chronic inflammation. The associations between MPO and the disease variables of RA patients support a role for MPO in the inflammatory process of the disease.
23973526 RhoA/ROCK-dependent pathway is required for TLR2-mediated IL-23 production in human synovi 2013 Nov 1 IL-23 is produced by antigen presenting cells and plays critical roles in immune response in rheumatoid arthritis. In this study, we investigated whether the RhoA/Rho-kinase pathway is required to elevate TLR2-mediated IL-23 production in synovial macrophages from patients with rheumatoid arthritis (RA), and then examined the suppressive effect of cilostazol on these pathways. IL-23 production was elevated by lipoteichoic acid (LTA), a TLR2 ligand, and this elevation was more prominent in RA macrophages than in those from peripheral blood of normal control. LTA increased the activation of RhoA in association with increased the nuclear translocation of NF-κB and its DNA-binding activity. Pretreatment of RA macrophages with the pharmacological inhibitors exoenzyme C3 (RhoA), Y27632 (Rho-kinase) or BAY11-7082 (NF-κB) inhibited IL-23 production by LTA. Inhibition of the RhoA/Rho-kinase pathway by these drugs attenuated NF-κB activation. Cilostazol suppressed the TLR2-mediated activation of RhoA, decreased NF-κB activity with down-regulated IL-23 production, and these effects were reversed by Rp-cAMPS, as an inhibitor of cAMP-dependent protein kinase. The expression of IL-23, which colocalized with CD68⁺ cells in knee joint of CIA mice, was significantly attenuated by cilostazol along with the decreased severity of arthritis. Taken together, the RhoA/Rho-kinase pathway signals TLR2-stimulated IL-23 production in synovial fluid macrophages via activation of NF-κB. Thus it is summarized that cilostazol suppresses TLR2-mediated IL-23 production by suppressing RhoA pathway via cAMP-dependent protein kinase activation.
23348744 iRHOM2 is a critical pathogenic mediator of inflammatory arthritis. 2013 Feb iRHOM2, encoded by the gene Rhbdf2, regulates the maturation of the TNF-α convertase (TACE), which controls shedding of TNF-α and its biological activity in vivo. TACE is a potential target to treat TNF-α-dependent diseases, such as rheumatoid arthritis, but there are concerns about potential side effects, because TACE also protects the skin and intestinal barrier by activating EGFR signaling. Here we report that inactivation of Rhbdf2 allows tissue-specific regulation of TACE by selectively preventing its maturation in immune cells, without affecting its homeostatic functions in other tissues. The related iRHOM1, which is widely expressed, except in hematopoietic cells, supported TACE maturation and shedding of the EGFR ligand TGF-α in Rhbdf2-deficient cells. Remarkably, mice lacking Rhbdf2 were protected from K/BxN inflammatory arthritis to the same extent as mice lacking TACE in myeloid cells or Tnfa-deficient mice. In probing the underlying mechanism, we found that two main drivers of K/BxN arthritis, complement C5a and immune complexes, stimulated iRHOM2/TACE-dependent shedding of TNF-α in mouse and human cells. These data demonstrate that iRHOM2 and myeloid-expressed TACE play a critical role in inflammatory arthritis and indicate that iRHOM2 is a potential therapeutic target for selective inactivation of TACE in myeloid cells.
24219428 Safety of anti-tumor necrosis factor agents in psoriatic arthritis - an update. 2014 Feb INTRODUCTION: Tumor necrosis factor (TNF) blockers have represented a real revolution in the treatment of rheumatoid arthritis and spondyloarthritides (SpAs). In the case of psoriatic arthritis (PsA), anti-TNF agents are much more effective than conventional disease modifying antirheumatic drugs on all manifestations of the disease, that is, axial involvement, peripheral arthritis, peripheral enthesitis, dactylitis and skin lesions. A complete understanding of their safety is fundamental in clinical practice. AREAS COVERED: This article addresses the safety of anti-TNF therapy in PsA. A systematic literature review was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE). The reported data were derived from randomized controlled trials, open-observational studies and meta-analyses. Useful information derived from the experiences in rheumatoid arthritis has also been reported. EXPERT OPINION: Anti-TNF therapies are as safe as conventional disease-modifying antirheumatic drugs in the management of psoriatic arthritis when the candidate patients are accurately selected. An adverse event could still occur when the patient is managed according to current national and/or international recommendations; therefore, tight controls aimed to detect adverse events early is mandatory.
25543267 Consensus statement on a framework for the management of comorbidity and extra-articular m 2015 Mar The objective of the study was to develop evidence-based and practical recommendations for the detection and management of comorbidity in patients with rheumatoid arthritis (RA) in daily practice. We used a modified RAND/UCLA methodology and systematic review (SR). The process map and specific recommendations, based on the SR, were established in discussion groups. A two round Delphi survey permitted (1) to prioritize the recommendations, (2) to refine them, and (3) to evaluate their agreement by a large group of users. The recommendations cover: (1) which comorbidities should be investigated in clinical practice at the first and following visits (including treatments, risk factors and patient's features that might interfere with RA management); (2) how and when should comorbidities and risk factors be investigated; (3) how to manage specific comorbidities, related or non-related to RA, including major adverse events of RA treatment, and to promote health (general and musculoskeletal health); and (4) specific recommendations to assure an integral care approach for RA patients with any comorbidity, such as health care models for chronic inflammatory patients, early arthritis units, relationships with primary care, specialized nursing care, and self-management. These recommendations are intended to guide rheumatologists, patients, and other stakeholders, on the early diagnosis and management of comorbidity in RA, in order to improve disease outcomes.
23070992 Hospitalizations of patients treated with anti-tumor necrosis factor-α agents -- a retros 2013 Jan OBJECTIVE: To assess the association between treatment with anti-tumor necrosis factor-α (TNF-α) agents and the occurrence of hospitalizations, their causes and complications, compared to treatment with traditional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). METHODS: A retrospective cohort study was conducted of patients with RA, AS, and PsA treated with anti-TNF-α agents between April 2002 and December 2007. Patients were assessed during the period of anti-TNF-α treatment (Group B) and compared to an equivalent period before initiation of anti-TNF-α therapy (Group A). All hospitalization charts were reviewed and diagnoses, comorbidities, concomitant medications, and clinical course were analyzed. Statistical analysis was performed using multivariate mixed Poisson regression. RESULTS: In the study period of 57 months, 735 hospitalization events of 327 patients were analyzed. Statistically significant decreases were seen in the total number of hospitalization events as well as hospitalizations due to exacerbation of rheumatic diseases in Group B compared to Group A (44.4 vs 74.2 and 21.9 vs 47.5 per 100 patient-years, respectively; p < 0.0001). More infectious events (7.4 in Group B compared to 4.6 per 100 patient-years in Group A; p = 0.043) were associated with anti-TNF-α treatment, older age, and underlying disease, because patients with RA had higher rates of infections compared to patients with PsA and patients with AS. CONCLUSION: The overall effect of anti-TNF-α therapy was a significant decline in total hospitalization events. The decrease was more prominent in patients with RA than in patients with AS and patients with PsA, and reflected the significant decrease in hospitalizations due to rheumatic disease exacerbation. The decrease was more pronounced than the observed increase in infectious events.
24339699 A clinical trial and extension study of infliximab in Korean patients with active rheumato 2013 Dec Currently, infliximab is given for disease control for active rheumatoid arthritis (RA) patients despite methotrexate treatment. However, the efficacy and safety of infliximab in Korean patients has not been assessed appropriately. Therefore, we performed placebo-controlled, double-blind, randomized study and extension study. One-hundred forty-three patients with active RA were randomized to receive placebo or infliximab 3 mg/kg intravenously at week 0, 2, 6, 14, and 22 with methotrexate maintenance. Primary endpoint was American College of Rheumatology 20% improvement criteria (ACR20) at 30 week. After the clinical trial, patients on placebo (Group 1) and patients on infliximab who showed ACR20 response (Group 2) were treated with infliximab through another 84 week for evaluation of safety. During clinical trial, patients in infliximab group showed higher ACR20 at week 30 than patients in placebo group (50.1% vs 30.6%, P=0.014). A total of 92 patients participated in the extension study. The maintenance rate of infliximab was 62.0% at 84 weeks of extension study. The overall rate of adverse events was not different between Group 1 and Group 2. In Korean patients with active RA despite methotrexate treatment, infliximab in combination with methotrexate is effective and the long-term treatment with infliximab is well tolerated. (ClinicalTrials.gov No. NCT00202852, NCT00732875).
25016825 The relationship between SNPs in the genes of TLR signal transduction pathway downstream e 2014 May Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLRs have been reported to be associated with rheumatoid arthritis (RA). This study was conducted to investigate correlation between SNP of downstream mononucleotide in signal transduction of Toll-like receptors and predisposing genes of RA. There was obviously correlative between single nucleotide polymorphism and predisposing genes of RA. G-type of IL-1RAP rs766442 may be protecting genes of RA, while T-type alleles of IL-6R rs11265618 and IL-1RAP rs766442 may be susceptible genes of RA. In conclusion, the studies on the nucleis acid polymorphism in TLRs signal pathway contribute to disclose genes' influence on the attack mechanism of RA, early diagnosis and treatment of RA.
23149905 New-onset multiple sclerosis associated with adalimumab treatment in rheumatoid arthritis: 2013 Feb Tumor necrosis factor (TNF) antagonists have brought about a significant advancement in treatment for autoimmune diseases such as rheumatoid arthritis (RA) and Crohn's disease; however, they are accompanied with a risk of severe adverse effects. We report the case of a 68-year-old female with a 33-year history of RA that developed multiple sclerosis (MS) during adalimumab (ADM) treatment at 22 months after the initial administration. Her first neurological symptom was mild dizziness, which progressed to severe dizziness with gait disturbance within 2 weeks. Fortunately, when she had this neurological disorder, ADM treatment was being transiently stopped because she was in the perioperative period. Repeated magnetic resonance imaging examinations revealed multiple demyelinating lesions in her brain, leading to the diagnosis of MS. The patient completely recovered spontaneously from the symptoms in several days. A review of the literature revealed another 15 cases of MS associated with anti-TNF-α treatment, emphasizing the importance of detecting neurological symptoms and discontinuing the anti-TNF-α therapy.
24800661 Therapeutic efficacy of three bispecific antibodies on collagen-induced arthritis mouse mo 2014 Jul Interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are inducible factors and important cytokines in the pathogenesis of rheumatoid arthritis (RA). In the present study, three bispecific and neutralizing antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1β and hIL-17A were constructed, their therapeutic efficacy was compared on collagen induced arthritis (CIA) model mice. In vitro assays demonstrated that the three antibodies could simultaneously bind to target both hIL-1β and hIL-17A. Mice with CIA were subcutaneously administered with one of three antibodies every two days for 29 days, we noticed that, compared with the BsAB-2 and BsAB-3, BsAB-1 antibody therapy resulted in more significant effect on alleviating the severity of arthritis by preventing bone damage and cartilage destruction and substantially decreasing production of CII-specific antibodies. In addition, BsAB-1 antibody was more potent in the inhibition of mRNA expression of IL-2, IL-1β, IL-17A, TNF-α and MMP-3 in the spleen of CIA mice compared to the other two. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 for the treatment of RA model mice, and may be chosen as an ideal candidate for further development of therapeutic drugs for treatment of RA.
23773882 Arthritis mimicking sports-related injuries. 2013 Jul Arthritis, including inflammatory, crystal deposition, and synovial proliferative disorders, may mimic sports injury. The purpose of this article is to review the clinical and radiologic findings of arthropathies that can present in athletes and be confused with internal derangement.
24196384 Therapeutic drug monitoring in rheumatic diseases: utile or futile? 2014 Jun Rapid and effective suppression of inflammation is a primary goal in the treatment of rheumatic diseases. However, the therapeutic effect of most medications may be slow to manifest, in the order of weeks or months in the case of DMARDs. Monitoring of drug concentrations allows the possibility of appropriate dose adjustment or changes in medication to achieve more rapid or better outcomes. We review the evidence for drug concentration monitoring. Despite the theoretical utility for monitoring of MTX polyglutamate concentrations in red blood cells in patients with RA, studies have not shown a clear association between concentrations and either efficacy or toxicity and routine measurement is not yet recommended. Small studies associating disease control with concentrations of anti-TNF therapies and anti-drug antibodies suggest that routine monitoring may be useful in the future. However, the data are not yet sufficient for this recommendation. With the use of allopurinol in gout, there is a putative therapeutic range for the active metabolite oxypurinol; however, adjusting the allopurinol dose to achieve a target urate concentration is likely to be most effective, and measuring oxypurinol may be best suited to assessing drug adherence. Although measuring thiopurine metabolite concentrations with AZA therapy has been shown to be useful in IBD, studies in rheumatic diseases have so far failed to confirm a useful association between concentrations and disease control or drug toxicity. Whole blood concentrations of HCQ have been associated with disease control in SLE and future studies may be able to determine a therapeutic range.
25155522 Redox-mediated angiogenesis in the hypoxic joint of inflammatory arthritis. 2014 Dec OBJECTIVE: Inflammatory arthritis is associated with joint inflammation, synovial tissue proliferation, and degradation of articular cartilage and bone. Angiogenesis is an early and fundamental component of synovial inflammation. Oxygen metabolism is recognized as an important mediator of joint vascular remodeling. The aim of this study was to determine whether in vivo synovial hypoxia (tissue PO2 [tPO2 ]) and tumor necrosis factor (TNF) blocking therapy alter synovial vascular expression of NADPH oxidase (NOX) and how this action regulates angiogenic mechanisms. METHODS: NOX-2 protein and messenger RNA expression was examined in patients with inflammatory arthritis before and after receiving TNF inhibitor (TNFi) therapy and in mice with collagen-induced arthritis (CIA). Proangiogenic processes were assessed in human microvascular endothelial cells (HMVECs) following culture with NOX-2 activators (TNFα and 4-hydroxynonenal), small interfering RNA (siRNA) for NOX, and the inhibitor diphenyleneiodonium (DPI) under conditions of normoxia or 3% hypoxia. RESULTS: We demonstrated significantly increased NOX-2 expression in the joints of patients with inflammatory arthritis and the joints of mice with CIA as compared to controls. NOX-2 expression was higher in patients with synovial tPO2 levels <3% than in those with tPO2 levels >3% (P < 0.05), and correlated with in vivo macroscopic/microscopic measures of angiogenesis, such as vascularity and levels of vascular endothelial growth factor, angiopoietin 2, factor VIII, neural cell adhesion molecule, and α-smooth muscle actin (P < 0.05 for all). A decrease in NOX-2 expression was paralleled by an increase in in vivo tPO2 levels only in those patients who were defined as TNFi responders. In vitro NOX-2 activators and 3% hypoxia significantly promoted HMVEC migration, angiogenic tube formation, and secretion of proangiogenic mediators, effects that were blocked by siRNA for NOX-2 or the NOX-2 inhibitor DPI. CONCLUSION: We demonstrated that hypoxia activates NOX-2 protein expression, and NOX-2-induced oxidative stress may be an initiating factor in driving angiogenesis.
24066023 Copper bracelets and magnetic wrist straps for rheumatoid arthritis--analgesic and anti-in 2013 BACKGROUND: Folklore remedies for pain and inflammation in rheumatoid arthritis include the application of magnets and copper to the skin. Despite the popular use of devices containing magnets or copper for this purpose, little research has been conducted to evaluate the efficacy of such treatments. OBJECTIVE: To investigate whether the practice of wearing magnetic wrists straps, or copper bracelets, offers any specific therapeutic benefit for patients with rheumatoid arthritis. DESIGN: Randomised double-blind placebo-controlled crossover trial. METHODS: 70 patients, aged 33 to 79 years and predominantly female (n = 52), with painful rheumatoid arthritis were recruited from general practices within Yorkshire. Participants were randomly allocated to wear four devices in a different order. Devices tested were: a standard (1502 to 2365 gauss) magnetic wrist strap, a demagnetised (<20 gauss) wrist strap, an attenuated (250 to 350 gauss) magnetic wrist strap, and a copper bracelet. Devices were each worn for five weeks, with treatment phases being separated by one week wash-out periods. The primary outcome measured was pain using a 100 mm visual analogue scale. Secondary pain measures were the McGill Pain Questionnaire and tender joint count. Inflammation was assessed using C-reactive protein and plasma viscosity blood tests and by swollen joint count. Physical function was assessed using the Health Assessment Questionnaire (Disability Index). Disease activity and medication use was also measured. RESULTS: 65 participants provided complete self-report outcome data for all devices, four participants provided partial data. Analysis of treatment outcomes did not reveal any statistically significant differences (P>0.05) between the four devices in terms of their effects on pain, inflammation, physical function, disease activity, or medication use. CONCLUSIONS: Wearing a magnetic wrist strap or a copper bracelet did not appear to have any meaningful therapeutic effect, beyond that of a placebo, for alleviating symptoms and combating disease activity in rheumatoid arthritis. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN51459023 ISRCTN51459023.