Browse

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

ID PMID Title PublicationDate abstract
26953930 Label-free detection of immune complexes with myeloid cells. 2016 Jul The aim of this study was to provide proof-of-concept for quantitative and qualitative label-free detection of immune complexes through myeloid cells with imaging surface plasmon resonance. Surface plasmon resonance imaging was first applied to monitor the binding of human sera from healthy and rheumatoid arthritis (RA) patients to immobilized citrullinated RA-specific peptide antigens, histone citrullinated peptide 2 (HCP2) and viral citrullinated peptide 2 (VCP2). Next, the binding of monocytoid cell line U937 to the resulting immune complexes on the sensor surface was monitored. As control, binding of U937 was monitored to immunoglobulin (Ig)G subclasses simultaneously. Cell response results were compared to results of cyclic citrullinated peptide 2 (CCP2) enzyme-linked immunosorbent assay (ELISA), clinical RA diagnosis and antigen-specific antibody distribution of the samples. Human IgG3 triggered the most pronounced response, followed by IgG1 and IgG4, while IgG2 did not result in U937 cell binding. Serum samples obtained from RA patients resulted in a significantly increased cell response to VCP2 compared to healthy controls. The strength of cell response towards VCP2 immune complexes showed significant correlation with levels of antigen-specific IgA, IgG and IgG3. Cellular responses on VCP2 immune complexes showed significant association with both CCP2-based serological positivity and European League Against Rheumatism (EULAR) criteria-based clinical RA diagnosis. Immunoglobulin-triggered binding of monocytoid cells can be monitored using a label-free multiplex technology. Because these binding events are presumably initiated by Fc receptors, the system provides a tool for biological detection of autoantibodies with diagnostic value, here exemplified by anti-citrullinated antibodies. This provides added information to antibody levels, as interaction with Fc-receptor-expressing cells is also affected by post-translational modification of the immunoglobulins.
27142742 Equol suppresses inflammatory response and bone erosion due to rheumatoid arthritis in mic 2016 Jun Rheumatoid arthritis (RA) is a chronic and systemic autoimmune inflammatory disease. Typical pathological findings of RA include persistent synovitis and bone degradation in the peripheral joints. Equol, a metabolite of the major soybean isoflavone daidzein, shows superior bioactivity than other isoflavones. We investigated the effects of equol administration on inflammatory response and bone erosion in mice with collagen-induced arthritis (CIA). The severity of arthritis symptoms was significantly low in the equol-administered CIA mice. In addition, equol administration improved the CIA-induced bone mineral density decline. In the inflamed area of CIA mice, equol administration suppressed the expression of interleukin-6 and its receptor. Furthermore, equol reduced the expression of genes associated with bone formation inhibition, osteoclast and immature osteoblast specificity and cartilage destruction. These results suggest that equol suppresses RA development and RA-induced bone erosion by regulating inflammation and bone metabolism.
27036977 Persistence of babesiosis for >2 years in a patient on rituximab for rheumatoid arthritis. 2016 Jun We report a patient who was being treated with rituximab for rheumatoid arthritis who developed Babesia microti infection that persisted for 26 months despite prolonged anti-babesia drug therapy. The explanation for the persistence was likely to have been the long-term immunocompromising effects of rituximab, as evidenced by seronegativity for B. microti antibodies that lasted for more than 1 year after onset of infection.
26370008 Low Serum Levels of Interleukin 35 in Patients with Rheumatoid Arthritis. 2015 Oct Interleukin 35 (IL-35) is a newly discovered anti-inflammatory cytokine. Recent studies have indicated that it plays a crucial role in the pathogenesis of autoimmune diseases. In humans, IL-35 is predominantly secreted from regulatory T cells. This study aimed to measure serum IL-35 levels in patients with rheumatoid arthritis (RA) and in control individuals, and analyze its association with disease indicators of RA. One hundred patients with RA were recruited, and 50 volunteers were enrolled as healthy controls. Serum IL-35 levels were measured using an enzyme-linked immunosorbent assay kit. RA patients showed significantly lower serum levels of IL-35 compared with healthy controls (p < 0.001). RA patients suffering from erosive arthritis (n = 31) had lower IL-35 levels than those with non-erosive arthritis (n = 69, p = 0.022). In addition, serum IL-35 level was significantly lower in 22 patients with elevated percentage (> 75%) of neutrophils (p < 0.001). Correlation analysis indicated a significantly negative association between IL-35 and age, rheumatoid factor (RF), or percentage of neutrophils. In contrast, the serum IL-35 levels were not significantly different between patients with anti-cyclic citrullinated peptide (CCP) antibodies (n = 78) and those without anti-CCP antibodies (n = 22). However, among patients without anti-CCP antibodies, the serum IL-35 levels were lower in patients with erosive arthritis (n = 8) than those patients without erosion (n = 14) (p < 0.001), although no significant difference was detected in patients with anti-CCP antibodies. In conclusion, IL-35 plays a protective role in the pathogenesis of RA.
26590174 Value of ultrasonography as a marker of early response to abatacept in patients with rheum 2016 Oct OBJECTIVES: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). METHODS: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology-European League Against Rheumatism (OMERACT-EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT-EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2-5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. RESULTS: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2-5): -0.7 (95% CIs -1.2 to -0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. CONCLUSIONS: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. TRIAL REGISTRATION NUMBER: NCT00767325.
26266998 Pain in systemic inflammatory rheumatic diseases. 2015 Feb The sometimes intense, persistent and disabling pain associated with rheumatoid arthritis (RA) and spondyloarthritis frequently has a multifactorial, simultaneously central and peripheral origin, and it may be due to currently active inflammation or joint damage and tissue destruction caused by a previous inflammatory condition. The symptoms of inflammatory pain symptoms can be partially relieved by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in central pain regulation mechanisms, as in the case of the chronic widespread pain (CWP) characterising fibromyalgia. The importance of distinguishing CWP from inflammatory pain is underlined by the fact that drugs such as tumour necrosis factor inhibitors are expensive, and direct costs are higher in patients with concomitant CWP than in those without. The management of pain requires a combination approach that includes pharmacological analgesia, and biological and non-biological treatments because, although joint replacement surgery can significantly improve RA-related pain, it may only be available to patients with the most severe advanced disease.
27105894 Increased numbers of CD23(+) CD21(hi) Bin-like B cells in human reactive and rheumatoid ar 2016 Jul A unique population of CD23(+) CD21(high) B cells in inflamed nodes (Bin) has been shown to accumulate in lymph nodes (LNs) draining inflamed joints of TNF-transgenic (TNF-tg) mice. Bin cells contribute to arthritis flare in mice by distorting node architecture and hampering lymphatic flow, but their existence in human inflamed LNs has not yet been described. Here, we report the characterization of resident B-cell populations in fresh popliteal lymph nodes (PLNs) from patients with severe lower limb diseases (non-RA) and rheumatoid arthritis (RA) patients, and from banked, cryopreserved reactive and normal human LN single cell suspension samples. Bin-like B cells were shown to be significantly increased in reactive LNs, and strikingly elevated (>30% of total) in RA samples. Histopathology and immunofluorescence analyses were consistent with B follicular hyperplasia and histological alterations in RA vs. non-RA PLNs. This is the first description of Bin-like B cells in human inflamed LNs. Consistent with published mouse data, this population appears to be associated with inflammatory arthritis and distortion of LN architecture. Further analyses are necessary to assess the role of CD23(+) CD21(hi) Bin-like B cells in RA pathogenesis and arthritic flare.
26487241 Pain intensity, temperament traits and social support as determinants of trauma symptoms i 2016 Apr AIM: The main goal of our study was to investigate the relationship between age, duration of pain, pain intensity, temperament traits as postulated by the Regulative Theory of Temperament (RTT), social support dimensions and the level of trauma symptoms, as appear in post-traumatic stress disorder (PTSD) in a sample of 300 patients suffering from chronic pain in two groups comprised of 150 patients with a clinical diagnosis of rheumatoid arthritis (RA) and 150 patients with a clinical diagnosis of low-back pain (LBP). They were analyzed together as a one group of 300 patients with chronic pain. METHOD: Temperament was measured with the Formal Characteristics of Behaviour - Temperament Inventory (FCB-TI). Social support was tested with the Berlin Social Support Scales (BSSS). The Numerical Rating Scale (NRS-11) was used to measure pain intensity. The level of trauma symptoms was assessed with the Post-Traumatic Stress Disorder Factorial Version Inventory (PTSDF). RESULTS: The results of our study suggest that the intensity of pain, participants' age, Emotional Reactivity and Sensory Sensitivity as temperament traits, need for support, and actually received social support were related to the level of trauma symptoms. The sum of the squared semi-partial correlations showed that all six variables (age, pain intensity, Emotional Reactivity, Sensory Sensitivity, need for support and actually received support), account for 20% of the variance of general trauma symptoms level. CONCLUSION: The importance of temperament traits, social support and trauma symptoms should be taken into an account in psychotherapy accompanying pharmacotherapy for pain.
27050636 Deep clinical remission: an optimised target in the management of rheumatoid arthritis? Ex 2016 Jul OBJECTIVES: Treat-to-target strategy, aiming at clinical remission, has greatly improved the prognosis of RA. However, ultrasonographic subclinical synovitis is correlated with bone erosion and disease flare. The aim of this study was to evaluate whether deeper clinical remission (DAS28(ESR)≤1.98) reflects the better control of subclinical synovitis. METHODS: One hundred and twenty-six RA patients in clinical remission were enrolled in the study. Disease activity and ultrasongraphy were evaluated at baseline, and every 3 months during a 12-month follow-up. The power Doppler (PD) synovitis and synovial hypertrophy (SH) of 22 joints were recorded semi-quantitatively. The relationship between the extent of clinical remission, flare and ultrasonographic features was analysed. RESULTS: In 126 RA patients, 76 achieved deep clinical remission (defined as DAS28(ESR)≤1.98) and 50 achieved mild clinical remission (defined as 1.98
26891576 IMPACT OF MORNING STIFFNESS, EDUCATION, AND AGE ON THE FUNCTIONAL STATUS OF PATIENTS WITH 2015 The purpose of this study was to explore the relationship between disability status and duration of morning stiffness in hands with regard to age, level of education, and gender in patients with rheumatoid arthritis (RA). Also, the authors wanted to investigate this relationship with regard to the presence of rheumatoid factor, i.e., the serological status. A retrospective study was conducted in 250 patients with the classic form of RA (186 females, s64 males, mean age Xb = 49.96 y ears, range 25-60 years, disease duration 1-27 years, Xb = 6.41) previously diagnosed with RA according to the ACR (American College of Rheumatology 1987 criteria). All patients were in Steinbrocker functional classes II and III. The probability level was expressed by p < 0.01 and p < 0.05. The relationship between the variables was measured by point-biserial correlation. The correlation between duration of morning stiffness and functional class was positive but low [(r = 0.10, y = 0.00x + 2.37, p > 0.05) seronegative, (r = 0.12, y = 0.00x + 2.30, p > 0.05) seropositive]. High positive values were obtained for the linear correlation coefficient between duration of the disease and functional class (p < 0.01). Also, high values were obtained regarding the coefficient of correlation between age and functional class [(r = 0.29, p < 0.01) seronegative, (r = 0.47, p < 0.01) seropositive]. Uneducated patients were significantly more represented in functional class III [ 23 (50%) seronegative, 19 (42.2%) seropositive] than in functional class II [16 (20.3%) seronegative, 22 (27.5%) seropositive]. In conclusion, in this study of patients with rheumatoid arthritis, increased duration of morning stiffness was associated with functional disability. Functional disability increased with the duration of the disease, depended on age and educational level, and was more pronounced in older age, regardless of RA serological status. With regard to serological status and sex, the differences were non-significant.
25600705 Deficiency of fibroblast activation protein alpha ameliorates cartilage destruction in inf 2015 Jan 20 INTRODUCTION: Inflammatory destructive arthritis, like rheumatoid arthritis (RA), is characterized by invasion of synovial fibroblasts (SF) into the articular cartilage and erosion of the underlying bone, leading to progressive joint destruction. Because fibroblast activation protein alpha (FAP) has been associated with cell migration and cell invasiveness, we studied the function of FAP in joint destruction in RA. METHODS: Expression of FAP in synovial tissues and fibroblasts from patients with osteoarthritis (OA) and RA as well as from wild-type and arthritic mice was evaluated by immunohistochemistry, fluorescence microscopy and polymerase chain reaction (PCR). Fibroblast adhesion and migration capacity was assessed using cartilage attachment assays and wound-healing assays, respectively. For in vivo studies, FAP-deficient mice were crossed into the human tumor necrosis factor transgenic mice (hTNFtg), which develop a chronic inflammatory arthritis. Beside clinical assessment, inflammation, cartilage damage, and bone erosion were evaluated by histomorphometric analyses. RESULTS: RA synovial tissues demonstrated high expression of FAP whereas in OA samples only marginal expression was detectable. Consistently, a higher expression was detected in arthritis SF compared to non-arthritis OA SF in vitro. FAP-deficiency in hTNFtg mice led to less cartilage degradation despite unaltered inflammation and bone erosion. Accordingly, FAP(-/-) hTNFtg SF demonstrated a lower cartilage adhesion capacity compared to hTNFtg SF in vitro. CONCLUSIONS: These data point to a so far unknown role of FAP in the attachment of SF to cartilage, promoting proteoglycan loss and subsequently cartilage degradation in chronic inflammatory arthritis.
25431327 Can we prevent rapid radiological progression in patients with early rheumatoid arthritis? 2015 Jan The aim of this study is to test the performance of a matrix model to predict rapid radiological progression (RRP) in a study population of early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) patients. A matrix model using baseline CRP, erosion score, autoantibody status, and initial treatment choice to predict RRP (increase ≥5 points in Sharp-van der Heijde score (SHS) in 1 year) was derived from the BeSt study where patients with active RA (1987-criteria) were treated with initial monotherapy or combination therapy, aiming at low disease activity. In the IMPROVED study, patients with early RA (2010 criteria) and UA were initially treated with methotrexate and prednisone aiming at remission. A receiver operating characteristics (ROC) curve was used to assess the discriminative value of the model to predict damage progression in the IMPROVED population. Four hundred thirty-one out of 479 patients with RA and 106/122 with UA could be categorized as high, intermediate, low, or very low risk for RRP. One patient, with a very low risk profile, showed RRP. Thirty-two other patients (5 %) showed radiological progression ≥0.5 point SHS; none had a high risk profile and 22 had a very low risk profile. The area under the curve (AUC) of the ROC curve was 0.56 (95% CI 0.45; 0.68). A matrix model predicting RRP based on risk factors identified in recent onset active RA according to the 1987-criteria performed poorly in recent onset RA (2010 criteria) and UA. It appears that known risk factors for damage progression lose their impact with early remission steered treatment, so that RRP might be considered a phenomenon of the past.
27037326 Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early dis 2016 Jul The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft 'Guideline on clinical investigation of medicinal products for the treatment of RA' released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria.
27893851 Expression and Regulation of PIWIL-Proteins and PIWI-Interacting RNAs in Rheumatoid Arthri 2016 OBJECTIVE: The PIWIL (P-element induced wimpy testis like protein) subfamily of argonaute proteins is essential for Piwi-interacting RNA (piRNA) biogenesis and their function to silence transposons during germ-line development. Here we explored their presence and regulation in rheumatoid arthritis (RA). METHODS: The expression of PIWIL genes in RA and osteoarthritis (OA) synovial tissues and synovial fibroblasts (SF) was analysed by Real-time PCR, immunofluorescence and Western blot. The expression of piRNAs was quantified by next generation small RNA sequencing (NGS). The regulation of PIWI/piRNAs, proliferation and methylation of LINE-1 after silencing of PIWIL genes were studied. RESULTS: PIWIL2 and 4 mRNA were similarly expressed in synovial tissues and SF from RA and OA patients. However, on the protein level only PIWIL4 was strongly expressed in SF. Using NGS up to 300 piRNAs were identified in all SF without significant differences in expression levels between RA and OASF. Of interest, the analysis of the co-expression of the detected piRNAs revealed a less tightly regulated pattern of piRNA-823, -4153 and -16659 expression in RASF. In RASF and OASF, stimulation with TNFα+IL1β/TLR-ligands further significantly increased the expression levels of PIWIL2 and 4 mRNA and piRNA-16659 was significantly (4-fold) induced upon Poly(I:C) stimulation. Silencing of PIWIL2/4 neither affect LINE-1 methylation/expression nor proliferation of RASF. CONCLUSION: We detected a new class of small regulatory RNAs (piRNAs) and their specific binding partners (PIWIL2/4) in synovial fibroblasts. The differential regulation of co-expression of piRNAs in RASF and the induction of piRNA/Piwi-proteins by innate immune stimulators suggest a role in inflammatory processes.
26928615 [Frequency and severity of periodontitis among patients with rheumatoid arthritis]. 2015 Dec BACKGROUND: Periodontitis may have a triggering and aggravating role of various medical conditions, including rheumatoid arthritis. AIM: To evaluate the periodontal status in Chilean patients with rheumatoid arthritis (RA), treated in a public hospital. PATIENTS AND METHODS: A trained professional conducted a periodontal examination in 40 patients with RA aged 23 to 73 years (85% women). When present, the severity of periodontitis and its relationship with gender, smoking, age, corticosteroids dose and AR activity were assessed. AR activity was evaluated using the Disease Activity Score Calculator for Rheumatoid Arthritis (DAS 28). RESULTS: Thirty five of the 40 patients had periodontitis and in 13, it was severe. Men, smokers, and older patients had more severe stages. Patients using higher doses of corticosteroids had lower severity of periodontitis. No relationship between the severity of periodontitis and AR activity was found. CONCLUSIONS: Periodontitis is common and severe in patients with RA, and is influenced by gender, age, smoking and corticosteroid dose.
25716931 Subclinical atherosclerosis in patients with rheumatoid arthritis. A meta-analysis of lite 2015 May We performed a systematic review with meta-analysis and meta-regression of literature studies evaluating the impact of rheumatoid arthritis (RA) on common carotid artery intima-media thickness (CCA-IMT) and on the prevalence of carotid plaques. Studies evaluating the relationship between RA and markers of cardiovascular (CV) risk (CCA-IMT and prevalence of carotid plaques) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. A total of 59 studies (4,317 RA patients and 3,606 controls) were included in the final analysis, 51 studies with data on CCA-IMT (52 data-sets on 3,600 RA patients and 3,020 controls) and 35 studies reporting on the prevalence of carotid plaques (2,859 RA patients and 2,303 controls). As compared to controls, RA patients showed a higher CCA-IMT (mean difference [MD]: 0.10 mm; 95 % confidence interval [CI]: 0.07, 0.12; p < 0.00001), and an increased prevalence of carotid plaques (odds ratio [OR]: 3.61; 95 %CI: 2.65, 4.93; p< 0.00001). Interestingly, when analysing studies on early RA, the difference in CCA-IMT among RA patients and controls was even higher (MD: 0.21 mm; 95 %CI: 0.06, 0.35; p=0.006), and difference in the prevalence of carotid plaques was entirely confirmed (OR: 3.57; 95 %CI: 1.69, 7.51; p=0.0008). Meta-regression models showed that male gender and a more severe inflammatory status [as expressed by disease activity score in 28 joints (DAS28), C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR)] significantly impacted on CCA-IMT. In conclusion, RA appears significantly associated with subclinical atherosclerosis and CV risk. These findings can be useful to plan adequate prevention strategies and therapeutic approaches.
27148767 Investigational Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthri 2016 Aug INTRODUCTION: The Tec family of non-receptor tyrosine kinases comprises five members. The cellular expression and function of these kinases has implicated them as potential drug targets for the treatment of both malignant and autoimmune diseases. Most attention has focused on inhibitors of BTK kinase with ibrutinib already approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia. Multiple BTK inhibitors are being developed for both oncology and autoimmune disease indications. AREAS COVERED: BTK inhibitors being evaluated in rheumatoid arthritis are considered. Both inhibitors which have progressed to early clinical development, and those demonstrating activity in rodent models of arthritis are reviewed. These include both reversible and irreversible inhibitors of the kinase, most of which target the cysteine-481 residue of BTK. The selectivity of these inhibitors for Tec family kinases is considered. EXPERT OPINION: Developing inhibitors of any kinase to treat of rheumatoid arthritis has proved problematic with regard to both efficacy and selectivity. It is anticipated that the more selective BTK inhibitors may prove more useful in treating arthritis, with the use of reversible inhibitors possibly offering a better strategy. Chronic dosing may exacerbate the emergence of drug resistance, with resistant mutations already observed in ibrutinib-treated patients.
26228264 Walking is a Feasible Physical Activity for People with Rheumatoid Arthritis: A Feasibilit 2016 Mar BACKGROUND: Exercise has been recognized as important in the management of rheumatoid arthritis (RA). Walking is a low-cost and low-impact activity, requiring little supervision. It requires no specialist training, is suited to a variety of environments and is inherently a clinically meaningful measure of independence. The aim of the present study was to determine whether a designed walking programme for people with RA successfully facilitated regular physical activity in participants, without detriment to pain levels. METHODS: Thirty-three people with RA were recruited from Dunedin Hospital rheumatology outpatient clinics and enrolled in a walking randomized controlled trial (RCT) feasibility study. Participants were randomly allocated to the walking intervention (n = 11) or control (n = 22) groups. Control participants received a nutrition education session, and the walking intervention group received instructions on a walking route with three loops, to be completed 3-4 times per week. The walking route shape was designed so that the length of the walk could be tailored by participants. Both groups were assessed at baseline and six weeks later. The primary outcome measures were feasibility, acceptability and safety. The principal secondary outcome was change in walking speed after the intervention. Additional outcome measures were a step-up test, activity limitations (on the Health Assessment Questionnaire), global well-being (on the European Quality of Life Questionnaire), self-efficacy for managing arthritis symptoms, self-efficacy for physical activity, daily pedometer readings and a daily visual analogue scale for pain. RESULTS: Participants successfully completed the walk for the suggested frequency, indicating feasibility and acceptability. There were no reported adverse effects of participation and the walking intervention group did not have higher daily pain levels than the control group, indicating safety. The walking intervention group showed a pattern of improvements in self-efficacy and global well-being; no changes in these outcomes were noted in the control group. No outcome measure showed statistically significant between-group differences. CONCLUSIONS: Walking appears to be a feasible, acceptable and safe intervention for people with RA. These findings inform the design and power requirements of larger trials of structured walking interventions. Copyright © 2015 John Wiley & Sons, Ltd.
26290205 Cyclodextrin-Based Delivery Systems for Arthritic Diseases: From Development to Experiment 2015 Arthritics diseases, such as rheumatoid arthritis and osteoarthritis are chronic inflammatory and one of the most prevalent health conditions that cause disability (pain and functional limitation of joints). Despite the research advances, the treatment of those pathological conditions remains ineffective, since the pharmacological therapy is palliative, reducing only the symptoms and, in some cases, the chronic progression of the disease. In this context, the development of new formulations for controlled release would be interesting for reducing the number of injections and would also increase the patient compliance. In this article, we present a review of the cyclodextrin (CD)-based delivery systems focusing from conventional guest-host inclusion complexes and CD-polysulphates, until supramolecular architectures such as drug-CD-polymers conjugates, pseudorotaxanes, hydrogels as well as double-carrier systems and other systems. In particular, this article focuses the main CD-based delivery systems described in the literature emphasizing their possible administration by intra-articular route on the treatment of arthritic diseases, concentrating on their development and also performance as in vivo experimental therapeutic systems.
26395836 Biosimilars for the management of rheumatoid arthritis: economic considerations. 2015 Biologic drugs have proved highly effective for the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA). These drugs are often considered cost-effective for well-defined RA patient populations not responding adequately to conventional treatment, but are used first-line relatively rarely, partly due to high costs. Furthermore, not all clinically eligible patients can access biologics even as second-line therapy. Recently, there has been a rise in interest in 'biosimilar' drugs that are highly comparable to the 'reference medicinal product' (RMP) in terms of efficacy and safety but may generally be lower in price. This review summarizes the cost burden of RA and considers the potential role of biosimilars in reducing drug costs and increasing patient access to biologics.