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ID PMID Title PublicationDate abstract
20653466 Ultrasonography in early assessment of elderly patients with polymyalgic symptoms: a role 2011 Jan OBJECTIVE: To study the usefulness of ultrasonography (US) in predicting the diagnostic outcome in patients with polymyalgic symptoms. METHODS: Sixty-one elderly patients with polymyalgic syndrome were recruited in a secondary care setting and followed up in a prospective way. Clinical, laboratory, and US data obtained at onset were re-evaluated after 1 year when diagnostic outcome was defined. RESULTS: A diagnostic shift was observed in 32 polymyalgic patients (52%). Calcium pyrophosphate deposition disease (CPDD) was diagnosed in nine patients, elderly-onset rheumatoid arthritis (EORA) in 18, and elderly-onset spondyloarthritis (EOSpA) in five. In polymyalgia rheumatica (PMR) patients US demonstrated synovitis in 90% of cases, in both proximal (90%) and peripheral joints (41%). The best predictive US model for the definitive diagnosis of PMR comprised: the presence of subacromial-subdeltoid bursitis [odds ratio (OR) 5.603, p = 0.003], low frequency of wrist (OR 0.074, p < 0.001), metacarpophalangeal (OR 0.052, p < 0.001), and metatarsophalangeal effusion/synovitis (OR 0.107, p < 0.027), low frequency of knee menisci chondrocalcinosis (OR 0.091, p = 0.013), tendinous calcaneal calcifications (OR 0.078, p = 0.006), and Achilles enthesitis (OR 0.107, p = 0.027), and low power Doppler US (PDUS) scores at wrist (OR 0.052, p < 0.001). CONCLUSIONS: US and PDUS can be useful in distinguishing, at onset of disease, pure PMR from other diseases mimicking this condition.
20877307 The Japanese experience with biologic therapies for rheumatoid arthritis. 2010 Nov The unique genetic, environmental and medical backgrounds of people in Japan might influence the effectiveness and safety of biologic agents in patients with rheumatoid arthritis (RA). Indeed, clinical trials revealed higher response rates to some biologic agents (including infliximab, etanercept and tocilizumab) in patients with RA in Japan than patients treated with the same agents in Western countries, although response rates to adalimumab were comparable in both populations. The reasons why response rates to some biologic agents differ in Japanese individuals is currently under investigation. Post-marketing surveillance data have been collected for all patients with RA who were treated with biologic agents in Japan to monitor drug safety. These data clearly demonstrated that only ∼5% of these patients experienced adverse drug reactions to biologic agents, which were well tolerated. Pneumonia, tuberculosis, Pneumocystis jirovecii pneumonia and interstitial pneumonitis are considered important severe adverse reactions and risk factors for these adverse effects have been identified. Adverse drug reactions could exaggerate the risks associated with biologic therapy in Japanese patients with RA. Attempts have, therefore, been made to predict clinical response and adverse effects to enable personalized therapy with biologic agents and to optimize the outcomes of these patients.
20595114 Total ankle replacement: the results of 100 mobility total ankle replacements. 2010 Jul We describe the early results of a prospective study of 100 total ankle replacements (96 patients) at a single centre using the Mobility Total Ankle Replacement. At final review, six patients had died and five ankles (5%) had been revised, two by fusion and three by exchange of components. All remaining patients were reviewed at a minimum of three years. The mean follow-up was 43 months (4 to 63). The three-year survival was 97% (95% confidence interval (CI) 91 to 99). The four-year survival was 93.6% (95% CI 84.7 to 97.4). The portion of bony interface that was visible on plain radiograph was divided into 15 zones and a radiolucent line or osteolytic cavity was seen in one zone in 14 ankles. It was not seen in more than one zone. In five ankles it was > 10 mm in width. This study suggests that the early outcome of ankle replacement is comparable to that of other total joint replacements.
19644909 Detection of coronary artery lesions and myocardial necrosis by magnetic resonance in syst 2009 Aug 15 OBJECTIVE: Myocardium and coronary arteries can occasionally be affected in patients with systemic necrotizing vasculitides; however, such involvement has not been systematically assessed using cardiovascular magnetic resonance imaging (MRI). METHODS: Magnetic resonance angiography and contrast-enhanced MRI were applied for the assessment of coronary arteries (the left anterior descending [LAD], left circumflex [LCx], and right coronary artery [RCA]) and myocardium, respectively, in 39 patients with vasculitis who were asymptomatic for cardiac disease (16 with microscopic polyangiitis [MPA], 11 with Wegener's granulomatosis [WG], 9 with Churg-Strauss syndrome [CSS], and 3 with polyarteritis nodosa [PAN]). Data were compared with age-matched disease-control patients with rheumatoid arthritis (n = 20) or systemic lupus erythematosus (n = 13), and with healthy control individuals with normal coronaries (n = 40). RESULTS: Patients with MPA, WG, and PAN (but not with CSS) were found to display significantly increased maximal diameters of coronary arteries compared with healthy controls (for MPA and WG; P < 0.001 for LAD and RCA, and P < 0.01 for LCx) and with both disease-control groups (for only MPA; P < 0.01 for LAD and RCA, and P < 0.05 for LCx). Fusiform coronary aneurysms were detected in patients with MPA (4/16) and PAN (2/3), whereas coronary ectasias were evident in patients with MPA (14/16) and WG (2/11). The presence of myocardial necrosis (by assessment of late gadolinium-enhanced images) was identified only in patients with MPA (2/16) and CSS (3/8 studied). CONCLUSION: Cardiovascular MRI assessment of patients with systemic vasculitis revealed coronary ectatic disease in the majority of patients with MPA and PAN, as well as in several patients with WG. Myocardial necrosis can be detected in MPA and CSS.
19560051 Abatacept therapy and safety management. 2009 May OBJECTIVES: To elaborate a how-to-use abatacept material intended to help physicians in the management of patients with inflammatory diseases treated with this drug in routine practice. METHODS: 1) Selection of the relevant domains by a rheumatologists' panel; 2) Search for published evidence in each domain; 3) Elaboration of the clinical tool guide with a 3-level gradation of evidence (evidence-based medicine EBM, official recommendations and expert's opinion). The experts were 11 academic rheumatologists with a large experience in prescribing abatacept and in managing rheumatoid arthritis. They were all members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society dedicated to the inflammatory rheumatic diseases. Each fact sheet was reviewed by two other experts; 4) Regular updating based on medical literature and postmarketing surveillance data. RESULTS: Four domains were considered relevant: abatacept contraindications, management of side effects or associated diseases appearing during abatacept treatment, management of "practical situations" such as surgery or pregnancy, physician and patient information. After the literature analysis and discussion during an experts' meeting, a consensus was reached on: a pre-treatment checklist aimed at searching abatacept contraindications; a what-to-do document when facing side effects or associated diseases (autoimmune pathology, bacterial or viral infections, cardiovascular diseases, intolerance to abatacept, solid or haematological malignancy) or "practical situations" (surgery, pregnancy, vaccination, travel, drug-drug interactions); an example of standard information letter to be addressed to the attending physician (rheumatologist and general practitioner); an example of standard information letter to be addressed to the patient. CONCLUSION: Based on both an EBM approach and an expert's opinion approach, this abatacept clinical tool guide should provide assistance to all physicians attending patients treated with abatacept. For a better implementation in clinical practice, this tool guide will be available online at www.cri-net.com and regularly updated.
20212065 Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion 2010 Mar 15 DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders.
20175678 Team-based rehabilitation improves long-term aerobic capacity and health-related quality o 2010 PURPOSE: To examine the effect of an interdisciplinary, out-patient rehabilitation programme for patients with chronic inflammatory arthritis on aerobic capacity and health-related quality of life (HRQOL). METHOD: One hundred and seventy-four patients, 115 with peripheral arthritis (PA) (91 women, mean age 53 years, disease duration 16 years) and 59 with spondylarthropathies (SpA), (27 women, mean age 46 years, disease duration 14 years) were consecutively enrolled in 18 days of interdisciplinary rehabilitation. We report data from evaluations at inclusion, at discharge, and at 4 and 12 months using a sub-maximal treadmill test of aerobic capacity and the Nottingham Health Profile (NHP) (t-test). RESULTS: At inclusion, less than 20% of all patients tested had aerobic capacity classified as 'average' or better. At discharge, 41% (PA) and 54% (SpA) reached the 'average' level or better with improvements maintained for 12 months. The total NHP scores improved in both groups (mean change -12 (99%CI -15, -9) for PA; mean change -13 (99%CI -19, -8) for SpA) and were maintained. CONCLUSION: Aerobic capacity and HRQOL improved significantly in this interdisciplinary out-patient rehabilitation study, and improvements were maintained for 12 months. The preserved level of aerobic capacity after 12 months indicated a change to a more physically active lifestyle among the participants.
19328763 LCS mobile-bearing total knee replacement. A 10-year's follow-up study. 2009 May INTRODUCTION: For the last three decades total knee arthroplasty surgery has been facing the renewed choice of using a traditional fixed-bearing design or a mobile-bearing system. A growing number of surgeons have elected to increase their use of mobile-bearing prostheses. We wanted to assess the reliability, in our hospital of this alternative choice. HYPOTHESIS: Fixed-bearing and LCS mobile-bearing knees exhibit comparable long-term clinical and radiographic results. MATERIAL AND METHODS: Between January 1994 and December 1996, 126 LCS prostheses (DEPUY) were implanted by the same operator in 101 patients (mean age was 70.0 years). The predominant underlying pathology was osteoarthritis (113 prostheses); the posterior cruciate ligament was retained in 30% of these cases which permitted a tibial tray implantation using a PCR type meniscal-bearing component; 78 prostheses were cemented; 116 prostheses included a patellar button: 46 of these resurfaced patella featured a cementless metal implant and a mobile-bearing polyethylene insert. Overall function was assessed using the SF-12 and IKS scores, and on the basis of patients' satisfaction rate. Patients' review process took place between 1st October 2006 and 1st December 2006. Of the 101 patients, 59 were alive, 39 were clinically examined and 20 completed a self-assessment questionnaire; 32 had died and 10 were lost to follow-up. The average age of the patients still alive was 78 years (79 years for those operated on for osteoarthritis, 67 years for those operated on for rheumatoid polyarthritis); Mean follow-up period at the time of this review was 11.4 years. Mean body mass index (BMI) was 30.8 kg/m(2). RESULTS: No early infection was observed. Early complications included instability in one case, stiffness in six cases and resolutive patellar pain in three cases. Six prostheses necessitated to be revised. In the 39 reviewed patients (52 prostheses), the mean IKS knee score was 78/100, (range, 20 to 100/100), mean functional score was 66/100 (range, 0 to 100/100). Mean mobility in flexion was 105.8 degrees (range, 20 degrees to 135 degrees). The SF-12 quality of life score was assessed in 39 of the operated patients. Mean physical score was 37 (range, 22.6 to 61.2); mean mental score was 47 (range, 23.1 to 62.3). Seventeen patients were very satisfied, 18 satisfied (these combined categories representing 90% of patients), three were partially satisfied and one was unsatisfied. Forty-three radiographs were performed in 36 patients at the time of the follow-up visit: 39 of them included an A-P, a lateral and a patellar view at 30 degrees of flexion. Thirty-nine readings were normal. A radiolucent line beneath the tibial component was observed on three radiographs. An asymptomatic patellar tilt was reported in one instance. Mean tibial slope was 8 degrees (range, 1 degree to 11 degrees). DISCUSSION: Statistical analysis of these results demonstrates a significant and long-lasting improvement in the clinical score, an early improvement (both in respect to functional score and mobility) with a late minor deterioration of the quality of this initial improvement; a poorly significant negative correlation between mobility and BMI. Despite a high satisfaction rate, it does not quite match that obtained with hip arthroplasty. No correlation was found between the observed results and patient gender, prosthesis fixation method, type of prosthesis (PCR meniscal-bearings versus rotating platform, posterior cruciate ligament retention versus sacrifice), tibial slope, limb axis, and selected patellar treatment options. CONCLUSION: The mobile-bearing prostheses achieve results at least as good as comparable ones reported in other series; demonstrate a very low revision rate in relation to wear damages; and tolerate insufficient axis deformity corrections. LEVEL OF EVIDENCE: Level IV. Therapeutic study.
20628839 Interstitial lung disease in rheumatoid arthritis. 2010 Oct Rheumatoid arthritis (RA) is the most common systemic autoimmune disease in the United States, affecting 1% to 2% of the adult population. Although joints and synovium are the primary targets in this disorder, extra-articular manifestations involving the lungs can lead to significant morbidity and excess mortality. Among the various pulmonary complications that occur in RA, interstitial lung disease (ILD) is the most damaging, with effects ranging from subclinical inflammation/scarring to end-stage pulmonary fibrosis. New insights during the past several years have underscored the epidemiologic impact of clinically/functionally significant RA-associated ILD (RA-ILD) and have begun to identify factors contributing to the pathogenesis of this potentially devastating complication of RA. Despite these advancements, the complexity of RA-ILD and the lack of reliable predictors for disease progression highlight the need for improved biomarker development. Establishing such detailed molecular signatures will ultimately guide the application and timing of therapeutic agents that include immunomodulators as well as newly studied antifibrotic agents.
19473577 Ultrasonographic depiction of knee joint alterations in systemic lupus erythematosus. 2009 Mar OBJECTIVE: The aim of this study was to assess inflammatory changes within the knee joint of systemic lupus erythematosus (SLE) patients by using ultrasound (US). Rheumatoid arthritis (RA) patients and healthy subjects (HS) were evaluated as controls. US findings were correlated with disease activity parameters. METHODS: Twenty-six SLE patients were enrolled in the study, 25 RA patients and 15 HS were selected as controls. US was performed by two different experienced operators, using an Agilent-HP Image point Hx machine equipped with a 10 MHz linear transducer. Power Doppler (PD) was used to determine local synovial perfusion (PFR 700-1100 Hz; gain 60-65dB; low filter). Knee joints were examined bilaterally. US findings, expressed after consensus of the 2 operators, were correlated to clinical and serological parameters of disease activity. Statistical analysis was performed by the EPISTAT program. RESULTS: In SLE, synovitis was found in 21 knees (40%), joint effusion in 12 (23%), synovial proliferation in 12 (23%), positive PD signal in 5 (10%) and gastrocnemius-semimembranosus bursitis in 5 (10%). No erosions were detected. There was a significant difference respect to RA for synovitis (p<0.003), synovial proliferation (p<0.002) and positive PD signal (p<0.01). No correlation was found between US alterations and SLE disease activity parameters. In the HS group 1 patient showed mild synovial proliferation. CONCLUSION: This is the first study that investigates knee joint involvement in SLE by ultrasonography. US was able to depict inflammatory alterations in the articular tissues of SLE patients, revealing some common characteristics with RA, except for the presence of erosions. We believe that US might be of help in the global evaluation of SLE patients with inflammatory joint involvement, providing relevant information to the clinician.
19192975 Categorization of infliximab dose changes and healthcare utilization and expenditures for 2009 Feb OBJECTIVE: To evaluate how changes in infliximab dose influence resource utilization and expenditures for patients with rheumatoid arthritis (RA). RESEARCH DESIGN AND METHODS: A retrospective analysis using claims from January 1, 1999 through March 31, 2005 in the MedStat MarketScan databases for RA patients who had an increase, decrease, or no change in infliximab dose within 1 year of initiating therapy. Eligibility criteria included at least one claim with a diagnosis of RA and no biologic treatment within 6 months before the index infliximab claim, continuous health plan enrollment (commercial or Medicare) for 6 months before and 12 months after the index date, and three consecutive infliximab infusions. The index and final infliximab doses were estimated from claims data. RESULTS: Data were included for 1678 commercially insured patients and 616 Medicare-eligible patients; 45.4% and 39.3%, respectively, had an increase in dose, 24.7% and 43.2%, respectively, had a decrease in dose, and 29.9% and 17.5%, respectively, had no change in dose. Overall, resource utilization was higher in the increase-in-dose groups and lower in the no change-in-dose groups when compared with the decrease-in-dose groups for both cohorts. Medical costs were also highest for the increase-in-dose groups for both cohorts. Pharmacy expenditures for the no-change-in-dose groups were lower than the decrease-in-dose groups in both cohorts. CONCLUSIONS: An increase in dose was the most common dose change for the commercial cohort, while a decrease in dose was the most common dose change for the Medicare-eligible cohort. Patients with an increase in dose had the highest utilization and expenditures while those with no change in dose had the lowest levels. The nature of this utilization needs to be examined to better understand how dosing changes may influence medical utilization. Changes in dose were defined by the difference between the first and final doses and may not have captured changes in interim doses.
20942872 Rheumatoid arthritis: a role for immunosenescence? 2010 Aug Aging is accompanied by a progressive decline in the integrity of the immune system, a process known as immunosenescence. Pathological features typical of immune dysfunction in older adults, encompassing dysregulation of innate and adaptive immune responses, characterize rheumatoid arthritis (RA), an autoimmune disease whose incidence increases with age. Recent evidence suggests that certain features of immunosenescence, such as the decrease in T-cell generation and diversity, may contribute to the development of RA. Thus, physiological immunosenescence may render older adults susceptible to RA, and premature immunosenescence may contribute to the development of RA in young adults. In addition, other features of immunosenescence may result from the chronic immune stimulation that occurs in RA and lead to worsening of the disease. This article reviews the immunopathological features common to aging and RA and discusses the mechanisms by which immunosenescence may contribute to the development or progression of RA.
19917164 Glucocorticoid sparing effect of tumour necrosis factor alpha inhibitors in rheumatoid art 2009 Sep OBJECTIVE: To determine, in real life practice, the impact of anti-tumour necrosis factor (TNF)-alpha on glucocorticoid (GC) use in rheumatoid arthritis (RA) patients. METHODS: This systematic monocenter retrospective before-after study enrolled all RA patients who started their first anti-TNF-alpha treatment between January 2004 and December 2006 and were followed more than 3 months after anti-TNF-alpha initiation. Paired comparisons were performed to compare GC intake during the year before anti-TNF-alpha initiation and during the first year of treatment; each patient was his/her own control. Comparisons between patients who reduced their oral prednisone intake and those who did not, were also performed to identify variables associated with prednisone decrease. RESULTS: 110 patients were included (90 females/20 males, age: 42.1+/-14.4 years, disease duration: 10.6+/-10.2 years). Etanercept was prescribed in 70 (63.6%) patients, adalimumab in 35 (31.8%) and infliximab in 5 (4.6%). At anti-TNF-alpha initiation, 79 patients (71.8%) were taking oral prednisone (mean dose 7.3+/-2.6 mg/d). Of the 82 prednisone-users (74.5% of patients), 62 (75.6%) had lowered prednisone doses, whereas 12 (14.6%) and 10 (12.2%) patients had stable or increased doses, respectively. Twelve patients (15.2%) discontinued oral prednisone. Overall, a significant decrease of 28% of oral prednisone use was observed. The only factors associated with oral prednisone decrease were higher initial prednisone daily doses (p=0.04) and female sex (p=0.04). CONCLUSION: This study showed a significant GC sparing-effect of anti-TNF-alpha in RA patients in real life practice that was observed for oral, parenteral and intra-articular administration, as early as the first 3 months of treatment.
19551588 [Triple arthrodesis in treatment of degenerative hindfoot deformities: clinical, radiologi 2009 May INTRODUCTION: Triple arthrodesis is performed to reconstruct a painless plantigrad foot in cases of fixed and painful hindfoot deformity. Mid-term results of our patients after triple arthrodesis concerning clinical and functional as well as radiological outcome were assessed in this examination. PATIENTS AND METHOD: In the retrospective study, 24 feet in 20 patients with triple arthrodesis after degenerative hindfoot malposition were examined. Sampling was done consecutively. The average age of the patients was 62.8 years (40-79), mean follow-up-period was 21.5 months. The patients were examined using the AOFAS score, assessment of subjective satisfaction and X-rays. In addition, the position of the foot was analysed using dynamic pedobarography and gait analysis. RESULTS: In the examined population, the mean AOFAS score was 74 (+/- 12.41) out of 94 points, the improvement averaged 51 (+/- 14.72) points. 75 % of the patients had no or only slight pain, 8 % reported limitations in everyday life. Mobility of the ankle was more than 30 degrees for 9 patients (38 %) and between 15 and 30 degrees for 13 patients (54 %). 23 patients out of 24 were satisfied with the result of the surgery. In most cases, dynamic pedobarography showed a rather physiological pattern of plantar pressure distribution with increased pressure remaining in the midfoot area. Valgus position of the hindfoot was 2.8 degrees (+/- 2.9 degrees), gait analysis showed very good results in 11 cases and good results in 13 cases. Among the examined patients, two cases of wound healing disorders appeared, and one non-union of the talonavicular joint which had to be reoperated. In two cases, clinically relevant degenerative changes of the ankle were diagnosed. CONCLUSION: Triple arthrodesis using internal fixation followed by sufficient immobilisation is a good and reliable technique for the correction of fixed hindfoot deformities. A very high level of patient satisfaction and a good clinical outcome can be achieved. Plantar pressure distribution can be reconstructed to a satisfactory extent. Due to the relatively high rate of degenerative arthritis in adjacent joints, the decision upon performing a triple arthrodesis should be considered carefully. Clinical and radiological integrity of these joints are required.
21054657 Adherence, discontinuation, and switching of biologic therapies in medicaid enrollees with 2010 Sep OBJECTIVE: This study examined adherence, discontinuation, and switching of rheumatoid arthritis (RA) biologics over a 1-year period after initiation of the biologic treatment in Medicaid patients with RA. METHODS: The study sample consisted of Medicaid patients with RA in California, Florida and New York who had newly initiated etanercept (n=1359), anakinra (n=267), or infliximab (n=1012) between January 1, 2000 and December 31, 2002. Adherence (proportion of days covered (PDC)≥0.80), discontinuation (90-day continuous gap), and switching (initiation of second biologic within 90days of discontinuation date of index biologic) were measured during the 12-month postindex biologic initiation. Sensitivity analyses were conducted by varying the thresholds to define these measures. Logistic regressions examined the factors associated with RA biologic adherence and discontinuation. RESULTS: Anakinra users had the lowest mean PDC (0.36) and percent adherent patients (11%) followed by etanercept users (mean PDC: 0.57; % adherent: 32%) and infliximab users (mean PDC: 0.64; % adherent: 43%). All three groups had high discontinuation rates (41% etanercept, 76% anakinra, and 41% infliximab). Few patients who discontinued the index biologic switched to another biologic. Logistic regressions found that patients in Florida had lower odds of being adherent and higher odds of discontinuing their index biologic than patients in California. Anakinra users had lower odds and infliximab users had higher odds of being adherent than etanercept users. Anakinra users had higher odds of discontinuation than etanercept users. CONCLUSION: This study highlights the poor adherence to and premature discontinuation without concurrent switching of RA biologics that should raise concern for clinicians as well as payers.
20662070 Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rhe 2010 Nov OBJECTIVE: To investigate both the preclinical effects of blocking the chemokine receptor CCR5 and the clinical effects of this approach on the signs and symptoms of rheumatoid arthritis (RA) in patients with active disease. METHODS: Preclinical evaluations of AZD5672, a small-molecule antagonist of CCR5, were performed, including studies of ligand binding and chemotaxis. The pharmacokinetics of AZD5672 were assessed in both single- and multiple-dose studies in healthy volunteers. A randomized, placebo-controlled, phase IIb study was conducted in patients with active RA receiving methotrexate. Treatment arms were AZD5672 (20, 50, 100, or 150 mg orally, once daily), matched placebo, or open-label etanercept (50 mg subcutaneously, once weekly). The primary end point was the proportion of patients achieving a 20% improvement response on the American College of Rheumatology improvement criteria (ACR20) at week 12. Secondary end points included the ACR20 over time, as well as 50% (ACR50) and 70% (ACR70) improvement responses, changes in individual components of the ACR improvement criteria, and disease activity measured with the Disease Activity Score based on the 28-joint count. RESULTS: AZD5672 was a highly potent and selective antagonist of CCR5, displaying nonproportional steady-state pharmacokinetics while inhibiting internalization of CCR5 in an ex vivo macrophage inflammatory protein 1β stimulation assay in which AZD5672 was evaluated over the 20-150-mg dose range. In the phase IIb study testing this dose range in patients with RA (n = 371 patients randomized to received treatment), AZD5672 was generally well tolerated, with no unexpected adverse events. There was no statistically significant difference in the proportion of patients achieving an ACR20 response at week 12 between those receiving any dose of AZD5672 and those receiving placebo; etanercept was significantly more efficacious than AZD5672 and placebo. CONCLUSION: Despite a clear rationale for targeting CCR5, this clinical study showed that AZD5672, administered orally, did not have any clinical benefit, suggesting that CCR5 antagonism alone is unlikely to be a viable therapeutic strategy in RA.
20638271 Deficiencies in provision of integrated multidisciplinary podiatry care for patients with 2010 Jun BACKGROUND: Foot problems are highly prevalent in inflammatory arthritis (IA), especially rheumatoid arthritis (RA). Chronic inflammation can lead to permanent structural changes, deformity and disability. Early podiatry intervention in RA improves long term outcomes. National guidelines recommend that patients should be treated by a multidisciplinary team with dedicated podiatry services. In clinical practice funding constraints limit availability of these services. OBJECTIVES: To assess prevalence of foot problems and quality and availability of foot care services at a UK district general hospital. METHOD: 1200 IA patients in Swindon (Wiltshire, UK) were invited to complete an anonymised questionnaire regarding access to foot care services and education/information on foot problems. RESULTS: 448 patients. Prevalence of foot problems: 68%. Only 31% of patients had access to appropriate foot specialist. 24% had received foot assessment within 3 months of diagnosis of IA and 17% yearly review thereafter. CONCLUSIONS: Despite high prevalence of foot problems in our population we identified significant deficiencies in provision of integrated multidisciplinary podiatry care. The data we present could be used by others to support business cases to obtain funding to improve the links between rheumatology and podiatry services.
20797312 GP130 cytokines and bone remodelling in health and disease. 2010 Aug Cytokines that bind to and signal through the gp130 co-receptor subunit include interleukin (IL)-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and ciliary neutrophic factor (CNTF). Apart from contributing to inflammation, gp130 signalling cytokines also function in the maintenance of bone homeostasis. Expression of each of these cytokines and their ligand-specific receptors is observed in bone and joint cells, and bone-active hormones and inflammatory cytokines regulate their expression. gp130 signalling cytokines have been shown to regulate the differentiation and activity of osteoblasts, osteoclasts and chondrocytes. Furthermore, cytokine and receptor specific gene-knockout mouse models have identified distinct roles for each of these cytokines in regulating bone resorption, bone formation and bone growth. This review will discuss the current models of paracrine and endocrine actions of gp130-signalling cytokines in bone remodelling and growth, as well as their impact in pathologic bone remodelling evident in periodontal disease, rheumatoid arthritis, spondylarthropathies and osteoarthritis.
20821212 The balance between soluble receptors regulating IL-6 trans-signaling is predictive for th 2012 Jan The objective of this study is to investigate the relationship between soluble components of the interleukin 6 (IL-6) system mediating and modifying IL-6 trans-signaling and the RANKL-RANK-osteoprotegerin system in postmenopausal women with rheumatoid arthritis (RA). The following parameters were investigated in 126 postmenopausal women with RA: IL-6, soluble IL-6-receptor (sIL-6R), soluble glycoprotein 130 (sgp130), sRANKL, osteoprotegerin (OPG), osteocalcin, erythrocyte sedimentation rate and C-reactive protein in sera, pyridinolin and desoxypyridinolin crosslinks in the morning urine. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN). Predictors of RANKL/OPG ratio and BMD were evaluated by multiple linear regression analysis. The following determinants of the RANKL/OPG ratio were identified: sIL-6R/sgp130 ratio and daily glucocorticoid (GC) dose as positive determinants in the whole group (R (2) = 0.56; P = 0.001), sIL-6R/sgp130 ratio as the exclusive positive determinant in patients with GC therapy (R (2) = 0.48; P = 0.001) and sgp130 as negative determinant in patients without GC (R (2) = 0.42; P = 0.031). Sgp130 was highly significantly positively correlated with OPG in the whole group (P < 0.001) as well as in patients with (n = 70; P < 0.05) and without GC therapy (n = 56; P < 0.01). sIL-6R was the main negative predictor of BMD-LS (R (2) = 0.41; P = 0.019). High sIL-6R/sgp130 ratio and/or low sgp130 are associated with a high sRANKL/OPG ratio in sera of postmenopausal women with RA indicating the critical significance of IL-6 trans-signaling for an increase in the RANKL/OPG ratio and of bone resorption. Inhibition of IL-6 trans-signaling may be an effective bone-protecting principle in postmenopausal women with RA.
20471886 Use of glucocorticoids in rheumatoid arthritis - pratical modalities of glucocorticoid the 2010 Oct OBJECTIVE: To develop recommendations about the use of glucocorticoids in patients with established rheumatoid arthritis (RA) managed in everyday practice, using the evidence-based approach and expert opinion. METHODS: A three-step procedure was used: a scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; a systematic literature review was conducted by searching the Medline and Embase databases and the abstracts of meetings held by the Société Française de Rhumatologie (SFR), American College of Rheumatology (ACR), and European League Against Rheumatism (EULAR); and recommendations were developed and validated by a panel of experts based on the data from the literature review and on their experience. For each recommendation, the level of evidence and extent of agreement among experts were determined. RESULTS: The five questions pertained to the use of glucocorticoids in RA patients: role for intravenous glucocorticoid bolus therapy, role for intraarticular injections, and practical modalities of glucocorticoid administration and discontinuation. From the literature search, 93 articles were selected based on their titles and abstracts. Of these, 50 were selected for the literature review. Eight recommendations about the use of glucocorticoid therapy in everyday practice in patients with established RA were validated by a vote among all participating experts: bolus glucocorticoid therapy should be reserved for highly selected situations; triamcinolone hexacetonide is the preferred glucocorticoid for intraarticular therapy, and the joint should be rested for about 24h after the injection; for oral glucocorticoid therapy, agents with a short half-life taken once daily should be preferred; and when discontinuing glucocorticoid therapy, the patient and usual physician should be informed of the risk of adrenal insufficiency.