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ID PMID Title PublicationDate abstract
27005941 Alleviation of collagen-induced arthritis by the benzoxathiole derivative BOT-4-one in mic 2016 Jun 15 Autoimmune rheumatoid arthritis is characterized by chronic inflammation and hyperplasia in the synovial joints. Although the cause of rheumatoid arthritis is largely unknown, substantial evidence has supported the importance of immune cells and inflammatory cytokines in the initiation and progression of this disease. Herein, we demonstrated that the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) alleviated type II collagen-induced arthritis in a mouse model. The levels of pro-inflammatory cytokines are elevated in both human patients with rheumatoid arthritis and mice with collagen-induced arthritis. BOT-4-one treatment reduced the levels of pro-inflammatory cytokines in mice and endotoxin-stimulated macrophages. BOT-4-one treatment suppressed the polarization of Th1- and Th17-cell subsets by inhibiting the expression and production of their lineage-specific master transcription factors and cytokines, as well as activation of signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited mitogen-activated protein kinase and NF-kappaB signaling as well as the transcriptional activities and DNA-binding of transcription factors, including activator protein-1, cAMP response element-binding protein and NF-kappaB. Our results suggest that BOT-4-one may have therapeutic potential for the treatment of chronic inflammation associated with autoimmune rheumatoid arthritis.
25904914 Differential Effects of IL-17A and TNF-α on Osteoblastic Differentiation of Isolated Syno 2015 OBJECTIVE: TNF-α and IL-17A act on fibroblast-like synoviocytes (FLS) and contribute to cytokine production, inflammation, and tissue destruction in rheumatoid arthritis (RA). The aim of this study was to compare their effects on osteogenic differentiation of isolated FLS and on whole bone explants from RA and osteoarthritis (OA) patients. METHODS: Fibroblast-like synoviocytes and bone explants were cultured in the presence or absence of TNF-α and/or IL-17A. Mineralization of extracellular matrix of FLS was measured by alizarin red and alkaline phosphatase activity (ALP). mRNA expression was analyzed by qRT-PCR for Wnt5a, BMP2, and RUNX2, key genes associated with osteogenesis. IL-6 and IL-8 levels were measured by enzyme-linked immunosorbent assays. Bone explant structure was quantified by histomorphometry. RESULTS: In isolated OA and RA FLS, the combination of TNF-α and IL-17A induced matrix mineralization, increased ALP activity and expression of the osteogenesis-associated genes Wnt5a, BMP2, and Runx2, indicating an osteogenic differentiation. Wnt5a levels increased with TNF-α alone and in combination with IL-17A. BMP2 expression decreased with IL-17A and TNF-α after 12 h with OA FLS and 24 h with RA FLS. Runx2 expression decreased only with combination of TNF-α and IL-17A in OA FLS and with cytokines alone and combined in RA FLS. IL-6 and IL-8 production increased with IL-17A and/or TNF-α in both FLS and bone samples, especially from RA. Treatment of bone explants with cytokine combination increased ALP in OA but not RA samples. A decrease in bone volume was seen with cytokine combination, especially with RA explants. CONCLUSION: Differences were observed for the effects of IL-17A and TNF-α on osteogenic differentiation. In isolated FLS, increased osteoblastogenesis was observed, contrasting with the inhibitory effect in whole bone, specifically in RA. The net effect of IL-17A and TNF-α appears to depend on the disease state and the presence of other cells.
25847598 The role of Cas-L/NEDD9 as a regulator of collagen-induced arthritis in a murine model. 2015 May 15 Cas-L/NEDD9 is a cytoplasmic docking protein downstream of β1 integrin-mediated signaling pathway and is essential for cellular migration and β1 integrin-mediated costimulation of T cells. We previously found that increased number of Cas-L positive leukocytes migrated into the inflamed joints of HTLV-I tax transgenic mice which spontaneously develop polyarthritis, suggesting a role of Cas-L in rheumatoid arthritis (RA) pathophysiology. Our current study expanded these findings on the role of Cas-L/NEDD9 in the development of RA by analyzing the pathophysiological changes in a Nedd9(-/-) mouse collagen-induced arthritis (CIA) model. Nedd9(-/-) mice exhibited a decrease in arthritis severity as compared to Nedd9(+/+) mice. In addition, as being conducted bone marrow transplantation experiments with a CIA model, Nedd9(-/-)→Nedd9(+/+) transplant showed a decrease in the incidence and severity score of arthritis, compared to those of Nedd9(+/+)→Nedd9(-/-) transplant. For analysis of serum levels of various cytokines, IL-1β, IL-6, IL-17, TNF-α, IFN-γ and anti-collagen antibody were decreased, while IL-4 and IL-10 levels were increased, in Nedd9(-/-) mice as compared to those in Nedd9(+/+) mice. Furthermore, collagen-mediated cellular responses of lymphocytes isolated from spleen or affected lymph nodes of Nedd9(-/-) mice were reduced. Our results strongly suggest that Cas-L/NEDD9 plays a pivotal role in the pathophysiology of CIA, and that Cas-L/NEDD9 may be a potential molecular target for the treatment of RA.
27872812 Anti-Inflammatory Effects of the Essential Oils of Ginger (Zingiber officinale Roscoe) in 2016 Jul Ginger and its extracts have been used traditionally as anti-inflammatory remedies, with a particular focus on the medicinal properties of its phenolic secondary metabolites, the gingerols. Consistent with these uses, potent anti-arthritic effects of gingerol-containing extracts were previously demonstrated by our laboratory using an experimental model of rheumatoid arthritis, streptococcal cell wall (SCW)-induced arthritis. In this study, anti-inflammatory effects of ginger's other secondary metabolites, the essential oils (GEO), which contain terpenes with reported phytoestrogenic activity, were assessed in female Lewis rats with SCW-induced arthritis. GEO (28 mg/kg/d ip) prevented chronic joint inflammation, but altered neither the initial acute phase of joint swelling nor granuloma formation at sites of SCW deposition in liver. Pharmacologic doses of 17-β estradiol (200 or 600 μg/kg/d sc) elicited the same pattern of anti-inflammatory activity, suggesting that GEO could be acting as a phytoestrogen. However, contrary to this hypothesis, GEO had no in vivo effect on classic estrogen target organs, such as uterus or bone. En toto, these results suggest that ginger's anti-inflammatory properties are not limited to the frequently studied phenolics, but may be attributable to the combined effects of both secondary metabolites, the pungent-tasting gingerols and as well as its aromatic essential oils.
26647549 [Adult onset Still's disease with the initial symptom of pharyngalgia: a case report]. 2015 Sep Adult onset Still's disease is a rare inflammatory disease characterized by spiking fevers, arthritis/ arthralgias, typical salmon-colored bumpy rash, pharyngalgia, myalgia and possible involvement of visceral organs. The diagnosis is exclusively based on clinical symptoms, according to the criteria, after the exclusion of well-known infectious, neoplastic, or other autoimmune/autoinflammatory disorders. This report includes one case of adult onset Still's disease with the initial symptom of pharyngalgia.
26985298 Discovery of 8-Amino-imidazo[1,5-a]pyrazines as Reversible BTK Inhibitors for the Treatmen 2016 Feb 11 Bruton's tyrosine kinase (BTK) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) pathway. It has become an attractive kinase target for selective B cell inhibition and for the treatment of B cell related diseases. We report a series of compounds based on 8-amino-imidazo[1,5-a]pyrazine that are potent reversible BTK inhibitors with excellent kinase selectivity. Selectivity is achieved through specific interactions of the ligand with the kinase hinge and driven by aminopyridine hydrogen bondings with Ser538 and Asp539, and by hydrophobic interaction of trifluoropyridine in the back pocket. These interactions are evident in the X-ray crystal structure of the lead compounds 1 and 3 in the complex with the BTK enzyme. Our lead compounds show desirable PK profiles and efficacy in the preclinical rat collagen induced arthritis model.
26272057 The prevalence of severe fatigue in rheumatic diseases: an international study. 2016 Feb Fatigue is a common, disabling, and difficult-to-manage problem in rheumatic diseases. Prevalence estimates of fatigue within rheumatic diseases vary considerably. Data on the prevalence of severe fatigue across multiple rheumatic diseases using a similar instrument is missing. Our aim was to provide an overview of the prevalence of severe fatigue across a broad range of rheumatic diseases and to examine its association with clinical and demographic variables. Online questionnaires were filled out by an international sample of 6120 patients (88 % female, mean age 47) encompassing 30 different rheumatic diseases. Fatigue was measured with the RAND(SF)-36 Vitality scale. A score of ≤35 was taken as representing severe fatigue (90 % sensitivity and 81 % specificity for chronic fatigue syndrome). Severe fatigue was present in 41 to 57 % of patients with a single inflammatory rheumatic disease such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Sjögren's syndrome, psoriatic arthritis, and scleroderma. Severe fatigue was least prevalent in patients with osteoarthritis (35 %) and most prevalent in patients with fibromyalgia (82 %). In logistic regression analysis, severe fatigue was associated with having fibromyalgia, having multiple rheumatic diseases without fibromyalgia, younger age, lower education, and language (French: highest prevalence; Dutch: lowest prevalence). In conclusion, one out of every two patients with a rheumatic disease is severely fatigued. As severe fatigue is detrimental to the patient, the near environment, and society at large, unraveling the underlying mechanisms of fatigue and developing optimal treatment should be top priorities in rheumatologic research and practice.
27069339 Pharmaceutical Approval Update. 2016 Apr Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey) for combination HIV-1 therapy; dapsone gel, 7.5% (Aczone) for acne vulgaris; extended-release tofacitinib (Xeljanz XR) for rheumatoid arthritis; and brivaracetam (Briviact) for epilepsy.
26222375 Anti-inflammatory and anti-arthritic activity of aqueous extract of Rosa centifolia in exp 2017 Sep AIM: The present study was carried out to evaluate the anti-inflammatory and antiarthritic activity of Rosa centifolia aqueous extract (RC) in a carrageenan-induced paw edema model and complete Freund's adjuvant (CFA)-induced arthritis. METHODS: Anti-inflammatory activity of RC was evaluated using the carrageenan-induced paw edema model in rats. Arthritis was induced in rats by sub-plantar administration of CFA. Joint size was measured at regular intervals by using a micrometer screw gauge. Serum and ankle joints of rats immunized with CFA were collected and subjected to enzyme-linked immunosorbent assay for estimation of tumor necrosis factor (TNF)-α level and dot blot for secretory cytokines interleukin (IL)-1β and IL-6. An acute and 28-day oral toxicity study was carried out to evaluate the safety of the test drug. RESULTS: Pre-treatment with RC produced a dose-dependent reduction in carrageenan-induced paw edema and CFA-induced arthritis models and was effective as indomethacin. RC also inhibited the delayed increase in joint diameter as seen in control and indomethacin-treated animals in CFA-induced arthritis. The expression of proinflammatory mediators TNF-α, IL-6 and IL-1β was also found to be less in the RC-treated group as compared to controls. CONCLUSION: Based on these results, it was suggested that Rosa centifolia could be considered as a potential anti-inflammatory and anti-arthritic agent.
26423309 IL-17-producing γδT cells are regulated by estrogen during development of experimental a 2015 Dec Interleukin-17 (IL-17) drives inflammation and destruction of joints in rheumatoid arthritis (RA). The female sex hormone 17β-estradiol (E2) inhibits experimental arthritis. γδT cells are significant producers of IL-17, thus the aim of this study was to investigate if E2 influenced IL-17(+) γδT cells during arthritis development using a variety of experimental RA models: collagen-induced arthritis (CIA); antigen-induced arthritis (AIA); and collagen antibody-induced arthritis (CAIA). We demonstrate that E2 treatment decreases IL-17(+) γδT cell number in joints, but increases IL-17(+) γδT cells in draining lymph nodes, suggesting an E2-mediated prevention of IL-17(+) γδT cell migration from lymph nodes to joints, in concert with our recently reported effects of E2 on Th17 cells (Andersson et al., 2015). E2 did neither influence the general γδT cell population nor IFNγ(+) γδT cells, implying a selective regulation of IL-17-producing cells. In conclusion, this study contributes to the understanding of estrogen's role in autoimmune disease.
30695328 [Molecular-Targeted Therapy and Autoimmune Disease]. 2016 Jun Recently, biological treatment agents such as antibody preparations have been widely used in clinical fields, and these agents provide benefits for many patients. They actually show effectiveness against lymphoma, as well as rheumatoid arthritis, which is an autoimmune disease. Accordingly, such biological treatment has altered the concept of treatment, from symptomatic therapy to maintenance of remission. However, it is a fact that there are also some patients for whom this treatment has little benefit. Antibodies for the treat- ment of rheumatoid arthritis can be divided into two groups: tumor necrosis factor (TNF) as cytokine signal blockade, and interleukin-6 (IL-6) as signal blockade from CTLA-4 on the T-cell membrane. It is well- known that the action mechanism of these biological treatment agents can affect the immune system. Thus, cases with side effects, including abnormal laboratory data, must be reported for further study. Since these agents are extremely expensive, their benefit will be marked only when biomarkers for the early detection of complications and prediction of beneficial effects are developed. The aim of this symposi- um is to discuss the role of the clinical laboratory in this molecular-targeted therapy. [Review].
29539537 The proximal ulna as an additional diagnostic feature of advanced rheumatoid arthritis. 2015 Sep Rheumatoid arthritis (RA) is considered to be an uncommon condition in paleopathology, although several case studies have recently been published. These studies tend to focus on changes in the small joints of the hands and feet, which are the most diagnostic, though these skeletal elements are often poorly preserved in archaeological contexts. This study aims to highlight another common trait that has been observed in multiple cases of RA in the clinical and paleopathological record: erosive lesions on the proximal ulna. RA frequently affects the elbow in clinical cases, with erosions observable in the radial head, the proximal ulna, and the distal humerus, in the later stages of the disease. Lesions produced by RA in the proximal ulna demonstrate a remarkable consistency in appearance between paleopathological cases from different periods and places. Although overlooked, erosive lesions on the proximal ulna provide an important diagnostic indicator of RA and yields additional information concerning disease progression.
27828639 Acrokeratosis verruciformis of Hopf - Case report. 2016 Sep A 54 year-old woman with a 3-year history of rheumatoid arthritis (RA) consulted us because of weight loss, fever and skin eruption. On physical examination, erythematous plaques with a pseudo-vesicular appearance were seen on the back of both shoulders. Histological examination was consistent with rheumatoid neutrophilic dermatosis (RND). After three days of prednisone treatment, the skin eruption resolved. RND is a rare cutaneous manifestation of seropositive RA, characterized by asymptomatic, symmetrical erythematous plaques with a pseudo-vesicular appearance. Histology characteristically reveals a dense, neutrophilic infiltrate with leucocitoclasis but without other signs of vasculitis. Lesions may resolve spontaneously or with RA treatment. This case illustrates an uncommon skin manifestation of active rheumatoid arthritis.
28053549 Persistence, switch rates, drug consumption and costs of biological treatment of rheumatoi 2017 OBJECTIVES: The aim of this analysis was to provide an estimate of drug utilization indicators (persistence, switch rate and drug consumption) on biologics and the corresponding costs (drugs, admissions and specialist care) incurred by the Italian National Health Service in the management of adult patients with rheumatoid arthritis (RA). METHODS: We conducted an observational retrospective cohort analysis using the administrative databases of three local health units. We considered all patients aged ≥18 years with a diagnosis of RA and at least one biologic drug prescription between January 2010 and December 2012 (recruitment period). Persistence was defined as maintenance over the last 3 months of the follow-up period of the same biological therapy administered at the index date. A switch was defined as the presence of a biological therapy other than that administered at the index date during the last 3 months of the follow-up period. Hospital admissions (with a diagnosis of RA or other RA-related diagnoses), specialist outpatient services, instrumental diagnostics and pharmaceutical consumption were assessed. RESULTS: The drug utilization analysis took into account only biologics with at least 90 patients on treatment at baseline (adalimumab n=144, etanercept n=236 and infliximab n=94). In each year, etanercept showed better persistence with initial treatment than adalimumab or infliximab. Etanercept was characterized by the lowest number of patients increasing the initial drug consumption (2.6%) and by the highest number of patients reducing the initial drug consumption (10.5%). The mean cost of treatment for a patient persisting with the initial treatment was €12,388 (€14,182 for adalimumab, €12,103 for etanercept and €11,002 for infliximab). The treatment costs for patients switching from initial treatment during the first year of follow-up were higher than for patients who did not switch (€12,710 vs. €11,332). CONCLUSION: Persistence, switch rate and drug consumption seem to directly influence treatment costs. In subjects not persisting with initial treatment, other health care costs were approximately three times higher than for persistent patients. This difference could suggest a positive effect on the quality of life for persistent patients. Etanercept showed the highest persistence with treatment.
27921071 Validation of automatic joint space width measurements in hand radiographs in rheumatoid a 2016 Oct Computerized methods promise quick, objective, and sensitive tools to quantify progression of radiological damage in rheumatoid arthritis (RA). Measurement of joint space width (JSW) in finger and wrist joints with these systems performed comparable to the Sharp-van der Heijde score (SHS). A next step toward clinical use, validation of precision and accuracy in hand joints with minimal damage, is described with a close scrutiny of sources of error. A recently developed system to measure metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints was validated in consecutive hand images of RA patients. To assess the impact of image acquisition, measurements on radiographs from a multicenter trial and from a recent prospective cohort in a single hospital were compared. Precision of the system was tested by comparing the joint space in mm in pairs of subsequent images with a short interval without progression of SHS. In case of incorrect measurements, the source of error was analyzed with a review by human experts. Accuracy was assessed by comparison with reported measurements with other systems. In the two series of radiographs, the system could automatically locate and measure 1003/1088 (92.2%) and 1143/1200 (95.3%) individual joints, respectively. In joints with a normal SHS, the average (SD) size of MCP joints was [Formula: see text] and [Formula: see text] in the two series of radiographs, and of PIP joints [Formula: see text] and [Formula: see text]. The difference in JSW between two serial radiographs with an interval of 6 to 12 months and unchanged SHS was [Formula: see text], indicating very good precision. Errors occurred more often in radiographs from the multicenter cohort than in a more recent series from a single hospital. Detailed analysis of the 55/1125 (4.9%) measurements that had a discrepant paired measurement revealed that variation in the process of image acquisition (exposure in 15% and repositioning in 57%) was a more frequent source of error than incorrect delineation by the software (25%). Various steps in the validation of an automated measurement system for JSW of MCP and PIP joints are described. The use of serial radiographs from different sources, with a short interval and limited damage, is helpful to detect sources of error. Image acquisition, in particular repositioning, is a dominant source of error.
27747579 Incidence of Gastrointestinal Perforations in Patients with Rheumatoid Arthritis Treated w 2016 Dec INTRODUCTION: The aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA). METHODS: Reporting rates of GIP events were estimated from three distinct patient data sets: a TCZ-IV RA clinical trial all-exposure population, a global TCZ postmarketing safety database population, and a US healthcare claims database population of patients with RA, including patients who received TCZ, anti-tumor necrosis factor (aTNF) agents, or abatacept. RESULTS: The clinical trial, global postmarketing, and healthcare claims populations provided 17,906, 382,621, and 3268 patient-years (PYs) of TCZ exposure, respectively. GIP incidence rates [95% confidence interval (CI)] were 1.9 (1.3-2.7), 1.2 (1.1-1.3), and 1.8 (0.7-4.0; specific definition) to 2.8 (1.3-5.2; sensitive definition) per 1000 PYs for the clinical trial, postmarketing, and healthcare claims populations, respectively. The GIP incidence rate (95% CI) for the comparator aTNF healthcare claims population ranged from 0.6 (0.3-1.2) to 0.9 (0.5-1.5) per 1000 PYs, for an absolute rate difference between TCZ and aTNFs of 1.2 (-0.3 to 2.5) to 1.9 (0.0-3.7) per 1000 PYs, corresponding to a number needed to harm between 533 and 828. CONCLUSION: The TCZ GIP event rates from multiple data sources were consistent with previously reported rates, did not increase over time, and were significantly associated with the number of prior biologics. Comparison of GIP incidence rates among patients with prior biologic exposure suggests that, for every 1000 patients treated with TCZ per year, an additional 1-2 GIP events might occur compared with patients treated with aTNFs. FUNDING: Roche.
27747515 Dosing of Intravenous Tocilizumab in a Real-World Setting of Rheumatoid Arthritis: Analyse 2016 Jun INTRODUCTION: In the United States, the recommended starting dose of intravenous tocilizumab (TCZ) is 4 mg/kg every 4 weeks, with an increase to 8 mg/kg based on clinical response for patients with moderate to severe rheumatoid arthritis; however, data on how TCZ dose is escalated in real life are missing. The objective of this analysis was to describe patterns of early intravenous TCZ dose escalation in a real-world setting using data from the Corrona registry. METHODS: All patients enrolled in the comparative effectiveness substudy (CERTAIN) nested within Corrona who initiated TCZ and completed 3- and 6-month study visits were eligible for inclusion. Patients who initiated TCZ 4 mg/kg were categorized into 1 of 2 groups: those who remained on TCZ 4 mg/kg at 3 months (Group 1) and those who escalated to TCZ 8 mg/kg by or at 3 months (Group 2). Changes in clinical disease activity measures were provided. RESULTS: Of the 213 patients who were eligible for analysis, 86 (40.4%) remained on their initial dose of TCZ 4 mg/kg (Group 1) and 110 (51.6%) were escalated to TCZ 8 mg/kg by or at 3 months (Group 2). Baseline demographic and clinical characteristics were similar between the 2 groups; except in Group 2, patients were older (58.3 vs. 54.0 years) and a lower proportion was female (75.5% vs. 89.4%) than in Group 1. Significant improvements in disease activity measures were observed at 3 and 6 months in both groups, with the majority of patients in both groups achieving moderate or good European League Against Rheumatism response. CONCLUSION: Real-world data demonstrated that physicians escalate TCZ dose at varying frequencies. The ability to administer TCZ in varying doses allows physicians to tailor TCZ therapy to disease activity. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01625650.
27536205 Discrepancies in assessment of patients with rheumatoid arthritis and secondary Sjögren's 2016 OBJECTIVES: To investigate whether a difference exists between DAS28 from CRP and DAS28 from ESR in patients with rheumatoid arthritis (RA) and secondary Sjögren's syndrome (sSS). MATERIAL AND METHODS: One group comprised patients with RA and sSS, the control group comprised patients with RA. The inclusion criteria for the RA and sSS group have been specified as follows: presence of at least one symptom of dryness, and also presence of anti-SS-A and anti-SS-B or at least focus score of one in biopsy. RESULTS: The disease activity score 28 (DAS28) was assessed using both ESR and CRP in 60 patients with RA and sSS and 59 patients with RA alone. However, concordance between these two methods was good (Cohen's κ coefficient κ = 0.60, 95% CI: 0.45-0.75 in the first group and κ = 0.71, 95% CI: 0.56-0.86 in the control group). In the group with RA and sSS, the mean value of DAS28-ESR = 5.2, whereas the mean value of DAS28-CRP = 4.7 (p < 0.0001). In the group with RA alone, mean DAS28-ESR = 4.7 while mean DAS28-CRP = 4.6; no significant difference was identified. Moreover, in RA patients with sSS, mean ESR = 39 mm/h compared with mean CRP at 25 mg/l. 79% of all patients demonstrated dysproteinaemia. There were connections between higher ESR and dysproteinaemia. In the control group there was no statistically significant difference between CRP and ESR. CONCLUSIONS: Both DAS28-ESR and DAS28-CRP are useful outcome measures in RA. However, in patients with RA and sSS, DAS28 should be evaluated based on CRP.
27042336 Predictive value of tender joints compared to synovitis for structural damage in rheumatoi 2016 OBJECTIVE: To evaluate the predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis (RA). METHODS: A post hoc analysis was performed on a prospective 2-year study of 59 patients with active RA starting on antitumour necrosis factor (TNF). Tenderness and synovitis was assessed clinically at baseline, followed by blinded ultrasound assessment (B-mode and power Doppler ultrasound (PDUS)) on the hands and feet (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal and 10 metatarsophalangeal (MTP) joints). Radiographs of these joints were performed at baseline and at 2 years. The risk of radiographic progression with respect to the presence of baseline tenderness or synovitis, as well as its persistence (after 4 months of anti-TNF), was estimated by OR (95% CI). RESULTS: Baseline tender joints were the least predictive for radiographic progression (OR=1.53 (95% CI 1.02 to 2.29) p<0.04), when compared to synovitis (clinical OR=2.08 (95% CI 1.39 to 3.11) p<0.001 or PDUS OR=1.80 (95% CI 1.20 to 2.71) p=0.005, respectively). Tender joints with the presence of synovitis were predictive of radiographic progression (OR=1.89 (95% CI 1.25 to 2.85) p=0.002), especially seen in the MTP joints. Non-tender joints with no synovitis were negatively predictive (OR=0.57 (95% CI 0.39 to 0.82) p=0.003). Persistence of tender joints was negatively predictive (OR=0.38 (95% CI 0.18 to 0.78) p=0.009) while persistence of synovitis was predictive (OR=2.41 (95% CI 1.24 to 4.67) p=0.01) of radiographic progression. CONCLUSIONS: Synovitis is better than tenderness to predict for subsequent structural progression. However, coexistence of tenderness and synovitis at the level of an individual joint is predictive of structural damage, particularly in the MTP joints. TRIAL REGISTRATION NUMBER: NCT00444691.
26225145 Dual X-Ray Absorptiometry Whole Body Composition of Bone Tissue in Rheumatoid Arthritis - 2015 Mar OBJECTIVES: Previous studies of bone tissue in rheumatoid arthritis (RA) using dual X-ray absorptiometry (DXA) concentrated on regions of interest that were used to diagnose osteoporosis. This study aimed to compare the whole body bone tissue (wbBT) of RA patients with healthy subjects and to identify the RA variables which significantly predict wbBT. METHODS: The study was cross-sectionally designed to include postmenopausal RA patients and age-matched healthy female controls. All 107 RA patients and all 104 controls underwent clinical examination, laboratory tests and whole body DXA composition, which recorded total and regional bone indices. Non-parametric standard statistical test and regression models after data normalization were used to assess correlations, associations and differences. RESULTS: Compared to controls, RA patients had significantly lower whole body and regional bone mass (14.9 kg compared to 15.5 kg; p = 0.031). Disease duration (r = -0.402 ; p < 0.001), C-reactive protein (r = -0.279; p = 0.015) and inflammation (2.5% wbBT compared to 2.9%; p = 0.043), radiographic damage (14.3 kg compared to 16.2 kg; p < 0.001), disease activity scores (r = -0.275 ; p = 0.018 for HAQ) are significantly correlated/associated with lower wbBT. Clinical structural damage is associated with lower wbBT and it can significantly predict them (R2 = 0.014; p = 0.001), while glucocorticoid treatment, even in low doses, was associated with lower wbBT percent (2.6% compared to 2.8%; p = 0.045). Treatment with biologics was associated with a lower rate of whole body osteoporosis (0% compared to 22.2%; p = 0.013). CONCLUSIONS: The main associated factors with the generalized bone loss in female RA patients are disease duration and disease activity. Clinical structural damage is the most powerful predictor of the whole body bone loss. These results suggest a general disturbance of skeletal bone metabolism in RA and could explain a greater risk of fragility fractures of non-central sites (e.g. ribs, tibia, ankles etc.) compared to post-menopause osteoporosis.